Showing posts with label Liver Cancer Treatment. Show all posts
Showing posts with label Liver Cancer Treatment. Show all posts

Friday, January 20, 2017

Successful phase 3 trial of drug for liver cancer

Successful phase 3 trial of drug for liver cancer
Date: January 18, 2017
Source: The Mount Sinai Hospital / Mount Sinai School of Medicine

Summary:
An international phase 3 trial has found that the drug regorafenib improved survival in patients with advanced hepatocellular carcinoma, a form of liver cancer, giving people who previously had no other options a better chance at survival. The trial included 152 sites in 21 countries.

An international phase 3 trial has found that the drug regorafenib improved survival in patients with advanced hepatocellular carcinoma (HCC), a form of liver cancer, giving people who previously had no other options a better chance at survival. Results from the study, which included researchers at The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, were recently published online in The Lancet. The trial, funded by Bayer, included 152 sites in 21 countries.

About 40 percent of HCC cases are diagnosed at advanced stages, a point when HCC is particularly difficult to treat. This trial provides evidence that regorafenib is the first systemic treatment for patients whose HCC progressed during treatment with sorafenib, the only other drug with proven clinical benefit.

This study tested regorafenib's effectiveness as a second-line therapy on 573 patients previously treated with sorafenib, 194 of whom were given a placebo. Regorafenib, a multikinase inhibitor, significantly improved overall survival, from 7.8 months on placebo to 10.6 months with regorafenib. Two patients treated with regorafenib had their tumor shrink to an undetectable level, according to the study.

"This study represents a breakthrough in the management of hepatocellular carcinoma, since it provides evidence for clinical benefits in an area that was an unmet medical need," said Josep M. Llovet, MD, founder and Director of the Liver Cancer Program and Professor of Medicine and Liver Diseases at the Icahn School of Medicine at Mount Sinai. "Regorafenib has shown it can improve survival in patients with advanced hepatocellular carcinoma progressing on sorafenib. Previously, no treatment was available for these patients."

Dr. Llovet was a member of the clinical trial's steering committee, and Charissa Chang, MD, Assistant Professor of Medicine and Liver Diseases at the Icahn School of Medicine, was principal investigator of the Mount Sinai testing site.

The success of this trial opens the field for testing drugs in third-line treatment of HCC and provides a rationale to test regorafenib as a first-line treatment or in combination with therapies administered directly into the tumor or diseased liver in patients in an earlier stage of HCC, according to Dr. Llovet. In this trial, regorafenib was well-tolerated with manageable adverse events, according to the paper in Lancet.

In January, Bayer announced that the U.S. Food and Drug Administration (FDA) had granted priority review status for Stivarga (regorafenib) as a second-line systemic treatment for patients with hepatocellular carcinoma. This research was also presented during the European Society of Medical Oncology's World Congress on Gastrointestinal Cancer in June.

Liver cancer is the second-leading primary cause of cancer-related deaths worldwide.

Story Source:
Materials provided by The Mount Sinai Hospital / Mount Sinai School of Medicine. Note: Content may be edited for style and length.

Journal Reference:
Jordi Bruix, Shukui Qin, Philippe Merle, Alessandro Granito, Yi-Hsiang Huang, György Bodoky, Marc Pracht, Osamu Yokosuka, Olivier Rosmorduc, Valeriy Breder, René Gerolami, Gianluca Masi, Paul J Ross, Tianqiang Song, Jean-Pierre Bronowicki, Isabelle Ollivier-Hourmand, Masatoshi Kudo, Ann-Lii Cheng, Josep M Llovet, Richard S Finn, Marie-Aude LeBerre, Annette Baumhauer, Gerold Meinhardt, Guohong Han. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet, 2017; 389 (10064): 56 DOI: 10.1016/S0140-6736(16)32453-9

Related:
Berlin, January 20, 2017 – Bayer today announced that the Japanese Ministry of Health, Labour and Welfare (MHLW) has granted priority review to Bayer Yakuhin, Ltd., Osaka, Japan, for regorafenib in the second-line treatment of patients with unresectable hepatocellular carcinoma (HCC).

January 4th, 2017
FDA granted priority review to an application seeking approval of Stivarga (regorafenib) for the second-line treatment of patients with hepatocellular carcinoma (HCC). Bayer noted that the priority review designation was supported by data from the Phase III RESORCE trial of patients with HCC whose disease progressed despite treatment with the company's drug Nexavar (sorafenib).

Wednesday, July 2, 2014

Liver Cancer Drug Fails to Live Up to Early Promise

Liver Cancer Drug Fails to Live Up to Early Promise
By -- Robert Preidt, HealthDay
Jul. 01, 2014 4:00PM PDT Jul. 01, 2014 4:00PM PDT TUESDAY, July 1, 2014 (HealthDay News) -- Although it looked promising in early studies, the drug everolimus didn't improve survival for people with advanced liver cancer in its latest trial, a new study found.

The findings from the phase 3 clinical trial are disappointing because earlier research suggested that everolimus (Afinitor) prevented tumor progression and improved survival for in advanced liver cancer. Normally, these patients can expect a median overall survival of less than one year.

The only drug currently shown to significantly improve survival of advanced liver cancer patients is sorafenib (Nexavar). But that drug's benefits are temporary and the cancer eventually progresses, according to background information in the new study.

The current study included 546 adults with advanced liver cancer whose disease progressed during or after treatment with sorafenib, or who could not take sorafenib. The patients were divided into two groups, with 362 given everolimus and 184 given a placebo.

There were no significant differences in overall survival between the two groups. There were 303 deaths (83.7 percent) in the everolimus group and 151 deaths (82.1 percent) in the placebo group. Median survival was 7.6 months with everolimus and 7.3 months with placebo.

The study appears in the July 2 issue of the Journal of the American Medical Association.

"The results from [this study] extend the list of failed phase 3 studies in advanced [liver cancer], highlighting the challenge of developing effective therapies for this cancer," wrote study author Dr. Andrew Zhu, of the Massachusetts General Hospital Cancer Center, Harvard Medical School, and colleagues.

More information
The U.S. National Library of Medicine has more about liver cancer.

Copyright © 2014 HealthDay. All rights reserved.

Wednesday, April 30, 2014

Can-Fite Submits Protocol to U.S. FDA for Phase II Liver Cancer Study

Can-Fite Submits Protocol to U.S. FDA for Phase II Liver Cancer Study

Tufts University will be a clinical site for international trial of CF102 with Orphan Drug Designation

PETACH TIKVA, Israel, April 29, 2014 /PRNewswire/ -- Can-Fite BioPharma Ltd. (NYSE MKT:CANF) (TASE:CFBI), a biotechnology company with a pipeline of proprietary small molecule drugs that address inflammatory and cancer diseases, announced today that it has submitted a study protocol to the U.S. Food and Drug Administration for its Phase II clinical trial of CF102 for the treatment of advanced liver cancer. The FDA has granted Orphan Drug designation to CF102 in this indication. The protocol, which has already been approved by the Institutional Review Board (IRB) in Israel, will also be filed in Europe.

The planned Phase II study will be conducted in Israel, Europe and the U.S. with 78 subjects who will be dosed with CF102 as a second-line treatment of advanced hepatocellular carcinoma (HCC) with Child-Pugh Class B cirrhosis. The study will investigate the efficacy and safety of CF102 as compared to placebo.

Dr. Keith Stuart, MD, assisted in developing the study protocol. He is Chairman, Department of Hematology at Lahey Clinic and Oncology Professor of Medicine, Tufts University School of Medicine. Tufts University will participate as the study's U.S. clinical site.

The protocol submission is supported by strong, positive data from Can-Fite's Phase I/II HCC study published in The Oncologist, and presented at the 18th World Congress on Advances in Oncology. The Phase I/II study data demonstrated that the trial objectives were successfully achieved. CF102 had a very favorable safety profile with very encouraging median overall survival and one patient who has been treated for 4 years with CF102. The A3 adenosine receptor (A3AR), which is the target of CF102, was also found to potentially serve as a biomarker to predict patients' reaction to treatment with CF102.

"We are planning to initiate our Phase II trial for advanced liver cancer during the current quarter. Having already received IRB approval in Israel, we look forward to the FDA's response to the protocol. Advanced liver cancer is an indication that is a clear, unmet medical need and we believe the FDA's Orphan Drug Designation for CF102 will support our clinical development path," stated Can-Fite CEO Dr. Pnina Fishman.

According to Global Industry Analysts, the global liver cancer drug market is expected to exceed $2 billion by 2015.

About CF102

CF102 is a small orally bioavailable drug which binds with high affinity and selectivity to the A3 adenosine receptor. The latter is highly expressed in tumor cells whereas low expression is found in normal cells. This differential effect accounts for the excellent safety profile of the drug. In our pre-clinical and clinical studies, CF102 induces a robust anti-tumor effect via de-regulation of the Wnt signaling pathway, resulting in apoptosis of liver cancer cells.

About Can-Fite BioPharma Ltd.

Can-Fite BioPharma Ltd. (NYSE MKT: CANF) (TASE: CFBI) is an advanced clinical stage drug development company with a platform technology that is designed to address multi-billion dollar markets in the treatment of cancer and inflammatory diseases. The Company's CF101 is in Phase II/III trials for the treatment of psoriasis and the Company is preparing for a Phase III CF101 trial for rheumatoid arthritis. Can-Fite's liver cancer drug CF102 is in Phase II trials and has been granted Orphan Drug Designation by the U.S. Food and Drug Administration. CF102 has also shown proof of concept to potentially treat other cancers including colon, prostate, and melanoma. These drugs have an excellent safety profile with experience in over 1,200 patients in clinical studies to date. For more information please visit: www.can-fite.com

Tuesday, February 4, 2014

ArQule Announces Commencement of Phase 3 Clinical Trial with Tivantinib in Hepatocellular Carcinoma by Partner Kyowa Hakko Kirin in Japan .

WOBURN, Mass.--(BUSINESS WIRE)--February 04, 2014--

ArQule, Inc. (Nasdaq: ARQL) today reported the announcement by its partner, Kyowa Hakko Kirin Co., Ltd. (Tokyo: 4151) of the initiation of a Phase 3 clinical trial evaluating tivantinib (ARQ 197) in Japanese patients with c-Met diagnostic-high inoperable hepatocellular carcinoma treated with one prior sorafenib therapy.

The trial is a randomized, double-blind placebo-controlled study to compare progression-free survival (PFS) in patients treated with tivantinib with those treated with placebo. Kyowa Hakko Kirin plans to enroll approximately 160 patients in this study.

"With the commencement of this study, two Phase 3 trials are now ongoing worldwide to evaluate the impact of tivantinib therapy in second line HCC," said Brian Schwartz, M.D., chief medical officer of ArQule. "We are also enrolling patients in the ongoing pivotal, randomized, double-blind METIV-HCC trial, being conducted in the West by ArQule and our partner, Daiichi Sankyo Co., Ltd., under a Special Protocol Assessment (SPA) agreement."

About MET and Tivantinib (ARQ 197)

Tivantinib is an orally administered, selective inhibitor of MET, a receptor tyrosine kinase, which is currently in Phase 2 and 3 clinical trials. In certain healthy adult cells, MET is present in low to normal levels to support natural cellular function, but in some cancer cells, MET is inappropriately and continuously activated. When abnormally activated, c-Met plays multiple roles in aspects of human cancer, including cancer cell growth, survival, angiogenesis, invasion and metastasis. The activation of certain cell signaling pathways, including MET, has also been associated with the development of resistance to EGFR inhibitors such as cetuximab.

Pre-clinical data have demonstrated that tivantinib inhibits MET activation in a range of human tumor cell lines and shows anti-tumor activity against several human tumor xenografts. In clinical trials to date, treatment with tivantinib has been generally well tolerated and has shown clinical activity in the tumors studied. Tivantinib has not yet been approved for any indication in any country.

About ArQule, Inc. and its Partners for the Development of Tivantinib

On December 19, 2008, ArQule and Daiichi Sankyo Co., Ltd. signed a license, co-development and co-commercialization agreement to co-develop tivantinib in the U.S., Europe, South America and the rest of the world, excluding Japan, China (including Hong Kong), South Korea and Taiwan, areas for which Kyowa Hakko Kirin has exclusive rights for development and commercialization under an exclusive license agreement signed with ArQule in 2007.

About ArQule

ArQule is a biotechnology company engaged in the research and development of next-generation, small-molecule cancer therapeutics. The Company's targeted, broad-spectrum products and research programs are focused on key biological processes that are central to human cancers. ArQule's lead product, in Phase 2 and Phase 3 clinical development, is tivantinib (ARQ 197), an oral, selective inhibitor of the c-MET receptor tyrosine kinase. The Company's pipeline includes: ARQ 092, designed to inhibit the AKT serine/threonine kinase and ARQ 087, designed to inhibit fibroblast growth factor receptor (FGFR). ArQule's current discovery efforts, which are based on the ArQule Kinase Inhibitor Platform (AKIP(TM)), are focused on the identification of novel kinase inhibitors that are potent and selective against their targets.

This press release contains forward-looking statements regarding the METIV-HCC clinical trial with tivantinib in hepatocellular carcinoma (HCC) conducted with Daiichi Sankyo and the Phase 3 clinical trial with tivantinib in HCC conducted by Kyowa Hakko Kirin as well as the Company's agreements with both Daiichi Sankyo and Kyowa Hakko Kirin. These statements are based on the Company's current beliefs and expectations, and are subject to risks and uncertainties that could cause actual results to differ materially. There can be no assurance that tivantinib alone or in a combination therapy will demonstrate promising therapeutic effects in pivotal or other trials; in addition, tivantinib may ultimately not demonstrate an appropriate safety profile in later stage or larger scale clinical trials, such as METIV-HCC or the Kyowa Phase 3 trial in HCC, including among patients with underlying cirrhosis and compromised liver function, as a result of known or as yet unanticipated side effects. The results achieved in later stage trials may not be sufficient to meet applicable regulatory standards or to justify further development. Problems or delays may arise during clinical trials or in the course of developing, testing or manufacturing tivantinib that could lead the Company, Daiichi Sankyo or Kyowa Hakko Kirin to discontinue development. Even if later stage clinical trials are successful, unexpected concerns may arise from analyses of data or from additional data. Obstacles may arise or issues may be identified in connection with review of clinical data with regulatory authorities, and regulatory authorities may disagree with the Company's view of the data or require additional data or information or additional studies. In addition, the planned timing of completion of clinical trials like METIV-HCC or the Phase 3 HCC trial conducted by Kyowa Hakko Kirin is subject to the ability of the Company or its partners to enroll patients, enter into agreements with clinical trial sites and investigators, and overcome ongoing or emergent regulatory issues and address other technical hurdles and issues related to the conduct of the trials for which each of them is responsible that may not be resolved promptly, or at all. Drug development involves a high degree of risk. Only a small number of research and development programs result in the commercialization of a product. Furthermore, ArQule may not have the financial or human resources to successfully pursue drug discovery in the future. Moreover, Daiichi Sankyo and Kyowa Hakko Kirin have certain rights to unilaterally terminate the tivantinib license agreement with the Company. If it were to do so, the Company might not be able to complete development and commercialization of tivantinib on its own. For more detailed information on the risks and uncertainties associated with the Company's drug development and other activities, see the Company's periodic reports filed with the Securities and Exchange Commission. The Company does not undertake any obligation to publicly update any forward-looking statements. CONTACT: ArQule, Inc.


William B. Boni, 781-994-0300

Tuesday, September 3, 2013

ArQule to cut liver cancer drug dose on safety concerns

 ArQule to cut liver cancer drug dose on safety concerns

(Reuters)
Drugmaker ArQule Inc said it would lower the dose of its experimental liver cancer drug for a second time, after a late-stage trial showed that patients on the therapy were becoming more susceptible to infection.

The company's shares fell as much as 20 percent as the setback comes after the drug, tivantinib, failed separate trials for lung and colorectal cancers.

Analysts were concerned about whether the latest cut in dose would affect the drug's efficacy.

ArQule and its Japanese partner Daiichi Sankyo Inc accepted the recommendation of an independent safety committee to reduce, from 240 mg twice daily to 120 mg, the dose to treat hepatocellular carcinoma - the most common form of liver cancer.

Last year, ArQule reduced the liver cancer drug dose to 240 mg from 360 mg during a mid-stage trial due to high incidence of anemia and neutropenia - a condition characterized by an abnormally low number of infection-fighting white blood cells.

"The key question is how effective the 120 mg dose will be in treating hepatocellular carcinoma," MLV & Co analyst George Zavoico told Reuters.

Zavoico said the company might have to stop the trial if the neutropenia incidence remains greater than expected, but added that this was unlikely to happen at the 120 mg dose.

"This is no doubt a string of bad luck, but whether or not it suggests that the drug will ultimately fail is premature," Zavoico said.

ArQule and Daiichi Sankyo stopped a late-stage trial of tivantinib to treat lung cancer last October, after determining that the drug did not improve patient survival.

Kyowa Hakko Kirin Co, which holds development rights for the drug in Japan and certain parts of Asia, halted its own lung cancer trial soon after, following a safety committee's recommendation.

About two months later, the drug failed a mid-stage trial on patients with colorectal cancer.

ArQule and Daiichi Sankyo said on Tuesday that they were unable to comment on whether the timeline for recruitment of the liver cancer trial would be delayed, as the study was in the early stages of recruitment.

ArQule shares were down 7.5 percent at $2.58 on the Nasdaq on Tuesday.

(Reporting by Esha Dey and Vrinda Manocha in Bangalore; Editing by Kirti Pandey)

http://www.reuters.com/article/2013/09/03/us-arqule-study-cancer-idUSBRE9820MT20130903

Thursday, August 8, 2013

Healio: Phase 3 trial assessing therapy for post-liver transplant HCV initiated



Phase 3 trial assessing therapy for post-liver transplant HCV initiated
August 8, 2013

Biotest AG has initiated treatment in a phase 3 clinical trial in North America of a therapy for patients who require liver transplantation because of hepatitis C infection, according to a press release.

The phase 3 trial will assess the efficacy, safety and pharmacokinetics of 10% hepatitis C hyperimmune globulin Civacir (Biotest AG) among patients with HCV undergoing liver transplantation, and will include 90 patients across the United States and Canada. The first patient began treatment after liver transplantation and several weeks of therapy with virostatics.

Treatment is intended to prevent HCV recurrence following liver transplant, as antiviral therapies can lead to tolerability and safety concerns in this patient population. It would be the first treatment approved for this indication, according to the release. The medication has received Orphan Drug designation in the United States and European Union, allowing for market exclusivity for 7 and 10 years, respectively, upon approval.

Exercise may reduce metabolic syndrome among liver transplant recipients
August 8, 2013
Liver transplant recipients were less likely to develop metabolic syndrome when reporting regular and more intense exercise in a recent study.

In a cross-sectional analysis, researchers evaluated 204 liver transplant recipients who had undergone transplantation more than 3 months before study enrollment (median 53.5 months). Height, weight, waist circumference and blood pressure were assessed, and patients reported the duration, frequency per week and metabolic equivalents (METS) of their physical activity.
Full Story »

Afinitor fails to meet survival endpoint for liver cancer indication
August 7, 2013

A global phase 3 study of everolimus as a treatment for patients with advanced liver cancer did not improve survival among users compared with placebo recipients, according to a press release.
Full Story »
 

Wednesday, August 7, 2013

Scoring tool predicts outcome of liver cancer treated with arterial embolization

Scoring tool predicts outcome of liver cancer treated with arterial embolization

Last Updated: 2013-08-06 13:49:06 -0400 (Reuters Health)

NEW YORK (Reuters Health) - A score based on four factors -- low albumin, high bilirubin and alfa-fetoprotein, and large tumor size -- is closely associated with mortality risk in patients with hepatocellular cancer (HCC) undergoing transarterial chemoembolization (TACE) or bland arterial embolization (TAE).

The scoring system "may help guide treatment selection, allow stratification in clinical trials and facilitate meaningful comparisons across reported series," according to the authors of the report in the Annals of Oncology online July 14.

As they explain, the prognosis is variable for patients with unresectable HCC for whom arterial embolization may be recommended, and a simple, reliable prognostic index would be valuable.

To develop such a scoring system, Dr. Tim Meyer at University College London and colleagues elsewhere in the UK first identified predictors of survival using data from a set of 114 patients treated with TACE/TAE. They then validated the findings in an independent dataset of 167 patients.

Cox regression analysis showed adjusted hazard ratios for mortality of 3.03 for albumin <36 g/dL; 2.21 for bilirubin >17 mcmol/L; 2.50 for alfa-fetoprotein >400 ng/mL; and 2.51 for a largest lesion >70 mm, according to the report.

The researchers assigned 1 point for each of those risk factors, and the sum of the points formed the individual prognostic score (termed the HAP score).

Median survival for a HAP score of 0, 1, 2 or >2 was 27.6, 18.5, 9.0, and 3.6 months, respectively.

The HAP score was equally predictive in the validation sample. In both cohorts, a HAP score of 2 or greater "defined poor prognosis groups which are unlikely to have benefited from TACE and might now be better served with systemic therapy or supportive care," Dr. Meyer and colleagues suggest.

Furthermore, the HAP score proved more accurate than five other scoring systems in identifying high- and low-risk groups, the team found.

Overall, they conclude, "We have defined a simple and clinically relevant prognostic index requiring the measurement of two tumour variables and two liver variables, specifically for patients undergoing TACE."

Still, they add, "It is appropriate to prospectively validate it on a larger cohort to confirm our findings."

SOURCE: http://bit.ly/16u95o8

Ann Oncol 2013.

Tuesday, July 2, 2013

Health-related QOL poorer during early HCV treatment with addition of telaprevir



Health-related QOL poorer during early HCV treatment with addition of telaprevir
Healio
Vera-Llonch M. Aliment Pharmacol Ther. 2013;38:124-133.
 
July 1, 2013
Patients with chronic hepatitis C experienced a temporary decrease to health-related quality of life during interferon-based therapy that was more pronounced with the addition of telaprevir in a recent study.
 
Researchers evaluated the health-related quality of life (HRQOL) of 722 patients with chronic HCV genotype 1 enrolled in the multicenter, phase 3, placebo-controlled, double blind ADVANCE study. All patients were treatment-naive and received either 48 weeks of therapy with pegylated interferon alpha-2a and ribavirin (PR; n=359), or 12 weeks of telaprevir with either 24 (T12PR24; n=210) or 48 weeks (T12PR48; n=153) of PR.
Read more....
 
Preliminary results suggest safety, efficacy of tremelimumab as HCC, HCV therapy
Sangro B. J Hepatol. 2013;59:81-88.
July 2, 2013
 
Patients with hepatocellular carcinoma and chronic hepatitis C may experience antiviral and antitumoral benefits from treatment with tremelimumab, according to results of a recent pilot study.
In the phase 2, noncontrolled, multicenter, open-label trial, researchers administered 15 mg/kg tremelimumab intravenously daily to 21 adult patients with chronic HCV genotype 1b and hepatocellular carcinoma (HCC) for 90 days for a maximum of four cycles or until severe toxicity or tumor progression occurred. Toxicity was evaluable in 20 participants and tumor response was measurable in 17 cases.
Read more....

Tuesday, May 7, 2013

TACE, sorafenib improve survival among patients with infiltrative HCC



TACE, sorafenib improve survival among patients with infiltrative HCC
May 7, 2013
Patients with infiltrative hepatocellular carcinoma experienced prolonged survival when treated with transarterial chemoembolization or sorafenib in a recent retrospective cohort study.
Researchers evaluated data from 155 patients with infiltrative hepatocellular carcinoma (iHCC) seen at the University of California, San Francisco Medical Center between 2002 and 2010. Participants had a median age of 60 years, MELD score of 13, maximum tumor diameter of 11.3 cm and alpha-fetoprotein level of 347 ng/mL.
Full Story »

Boceprevir/peginterferon/ribavirin effective, safe in chronic HCV patients with compensated cirrhosis
May 6, 2013
Patients with chronic hepatitis C and compensated cirrhosis experienced higher rates of sustained virologic response with the addition of boceprevir to therapy with pegylated interferon and ribavirin in a study presented at the International Liver Congress in Amsterdam.
Full Story »

Thursday, April 4, 2013

Role for Radiation in Locally Advanced Liver Cancer


Medscape Medical News > Oncology

Role for Radiation in Locally Advanced Liver Cancer

Radiation could play a role in the treatment of locally advanced hepatocellular carcinoma (HCC), according a prospective series of 102 patients treated with patient-specific stereotactic body radiation therapy (SBRT).

Results of the study were published online April 1 in the Journal of Clinical Oncology.

All patients had Child-Turcotte-Pugh class A disease and were unsuitable for standard locoregional therapies, report Alexis Bujold, MD, and colleagues from the University Health Network, University of Toronto, in Ontario, Canada. Most had underlying liver disease (38% hepatitis B, 38% hepatitis C, 25% alcohol-related). Patients in 2 trials received individualized SBRT (dose range, 24 to 54 Gy) in 6 fractions; results were then pooled.

The results show a 1-year survival rate of 55% and a median survival of 17 months after SBRT.

This compares favorably with results seen with the only other potential therapies available for this patient population, the researchers note. For best supportive care, the 1-year survival rate was 18% to 33% (median, 4.2 - 7.9 months); for sorafenib, the rate was 29% to 44% (median, 6.5 - 10.7 months).

These results add "to the growing body of evidence that liver tumors can be treated with durable local control with radiation," writes Theodore Hong, MD, from the Massachusetts General Hospital in Boston, in an accompanying editorial.

"However, the question of where radiation fits into the armamentarium of therapies for HCC remains," he continues.

Where Does Radiation Fit In?

Clearly, surgery remains the gold standard for localized disease, but only a small minority of patients with liver-confined HCC meets the tumor-specific and medical criteria for an operation, Dr. Hong points out.

For the remaining patients, therapeutic options include radiofrequency ablation and transarterial chemoembolization, but the efficacy of both of these is limited in larger tumors, he notes.

Another option is sorafenib, which has shown significant disease control in unresectable HCC, but the clinical activity is modest and the drug is associated with significant adverse effects, he explains.

Radiation is a potentially ablative liver-directed therapy that is complementary to existing options, and Dr. Hong suggests that the greatest benefits could be seen in high-risk patients. Significantly, this includes patients with tumor vascular thrombus, which is readily treatable with radiation therapy, he adds. Dr. Bujold and colleagues demonstrate that radiation therapy can be used to recanalize tumor-thrombosed vasculature.

However, randomized trials are needed to see if the "impressive local control" currently seen with radiation translates to a clinically meaningful survival benefit in patients with high-risk HCC, he cautions. Many previous series that have evaluated radiation therapy for HCC show results similar to those found by Dr. Bujold and colleagues: excellent local control but a precipitous drop in survival at 2 to 3 years.

New Trial Planned

Both the editorialist and the researchers discuss a planned trial that will address some of these issues. The Radiation Therapy Oncology Group (RTOG) is planning a randomized study comparing sorafenib alone with sorafenib plus SBRT in patients with HCC and vascular involvement.
"In addition to answering the question of whether radiation improves outcome in high-risk patients with HCC, this study will provide a significant education opportunity to the oncology community," writes Dr. Hong, because it includes imaging and contouring consensus guidelines in the protocol.
"Whether radiation is ready to be a new standard of care in high-risk patients with HCC will depend on meaningful support of this critical randomized trial," he concludes.

Dr. Bujold has disclosed no relevant financial relationships. Coauthor Laura Dawson, MD, reports receiving research funding from Bayer. Coauthor Morris Sherman, PhD, reports receiving remuneration from Arqule. Dr. Hong reports serving in a consultancy or advisory role for Illumina.
J Clin Oncol.

Published online April 1, 2013. Abstract, Editorial



Monday, February 11, 2013

Genetically Modified Smallpox Vaccine Effective In Liver Cancer Research [Study]

Genetically Modified Smallpox Vaccine Effective In Liver Cancer Research [Study]
By ANI

London, February 11(ANI): The virus used in the vaccine that helped eradicate smallpox is offering new hope to liver cancer patients.
 
Researchers have found that a genetically engineered version of the vaccinia virus tripled the average survival time of people with a severe form of liver cancer, with only mild, flu-like side effects, according to the New Scientist.

Thirty people with hepatocellular carcinoma received three doses of the modified virus - code-named JX-594 - directly into their liver tumour over one month. Half the volunteers received a low dose of the virus, the other half a high dose.

Results showed that members of the low and high-dose groups subsequently survived for, on average, 6.7 and 14.1 months respectively.

Two of the patients on the highest viral dose were still alive more than two years after the treatment.
As well as shrinking the primary tumour, the virus was able to spread to and shrink any secondary tumours outside the liver.

"Some tumours disappeared completely, and most showed partial destruction on MRI scans," noted David Kirn, head of the study at Jennerex. Moreover, the destruction was equally dramatic in the primary and secondary tumours.

The fact that the virus appears able to spread to secondary tumours suggests that simply injecting the virus into the bloodstream may be effective.

A trial to compare this treatment with injecting the virus directly into a tumour is under way.

Fischer said that until now, more than 200 people have received the virus, which has also shown promise against other types of cancer, including those of the kidney and skin.
But he warns that not everyone sees a benefit.
Source 

Press Release
 
Jennerex Announces Nature Medicine Publication HighlightingRandomized Overall Survival Benefit of Lead Product Candidate,Pexa-Vec (JX-594) in Patients With Advanced Hepatocellular Carcinoma(HCC)

High-Dose Pexa-Vec Associated With Statistically Significant Improvement in Median Survival Versus Low-Dose Pexa-Vec (14.1 Months vs. 6.7 Months)

SAN FRANCISCO, CA, Feb 10, 2013 (Menafn - MARKETWIRE via COMTEX) --Jennerex, Inc., a private, clinical-stage biotherapeutics companyfocused on the development and commercialization of best-in-classtargeted oncolytic immunotherapies for solid tumors, today announcedthe publication of research demonstrating the ability of its leadproduct-candidate, Pexa-Vec (JX-594) to significantly prolongsurvival in advanced hepatocellular carcinoma (HCC) patients in arandomized dose comparison clinical trial. This research, publishedin Volume 19, Issue 2 of Nature Medicine, showed a statisticallysignificant dose-dependent overall survival benefit with 14.1 monthsmedian overall survival for the high-dose group compared to 6.7months for the low-dose group (p-value = 0.02). This is the firstrandomized clinical trial of an oncolytic immunotherapy demonstratingsignificantly prolonged overall survival.

Pexa-Vec is an oncolytic immunotherapy designed to 1) rapidly de-bulktumors via tumor cell lysis, 2) activate an antivascular effect withrapid tumor vascular knockout, and 3) induce a durable immuneresponse against tumors. Pexa-Vec was engineered from vaccinia, whichhas been used for decades as a vaccine in healthy individuals.Pexa-Vec has been safely administered to over 200 patients and iscurrently in Phase 2b clinical development for the treatment ofadvanced HCC and is also being evaluated in other solid tumors.

"The treatment options for advanced HCC are limited, with fewpromising agents currently in development. This Nature Medicinepublication highlights the unique possibility of a meaningfulsurvival benefit combined with short-term, transient and manageableside effects," said Tony Reid, M.D., Ph.D., professor of Medicine atUniversity of California, San Diego and co-lead author of the paper."The findings also showed Pexa-Vec's ability to induce anti-tumorimmunity and reduce blood flow to tumors which supports Pexa-Vec'smulti-pronged approach to attacking cancer."

The data presented in the Nature Medicine publication showed thatPexa-Vec had clear local anti-cancer response at both the low andhigh doses. Thirty subjects were randomized into the low and highdose groups and received three Pexa-Vec treatments over the course offour weeks. The results demonstrated that Pexa-Vec treatment at bothdoses resulted in a reduction in tumor size and decreased blood flowin tumors. The data further demonstrates that Pexa-Vec treatmentinduced an immune response against the tumor, evidenced byantibody-mediated tumor cell toxicity. Pexa-Vec was well-tolerated atboth high and low doses with the most frequent adverse eventsconsisting of fever lasting less than 24 hours.

"This Nature Medicine publication validates our clinical data and thescientific rationale for our approach to treating cancer withoncolytic immunotherapy as well as the continued development ofPexa-Vec for the treatment of HCC and other solid tumors," saidLaurent Fischer, M.D., president and chief executive officer ofJennerex. "The opportunity to rapidly de-bulk tumors and provide along-term immune effect is a significant advance in the treatment ofHCC. We are currently enrolling patients in multiple mid andlate-stage trials with Pexa-Vec with the goal of bringing thisgroundbreaking therapy to market."

Pexa-Vec Clinical Development Program and SOLVE Platform Pexa-Vec(JX-594) is currently being evaluated in an international, randomizedPhase 2b clinical trial (TRAVERSE) in patients with advanced primaryliver cancer who have failed sorafenib therapy. It is also beingtested in HCC patients in combination with sorafenib. In addition,Pexa-Vec is being evaluated in a Phase 1-2 clinical trial in patientswith treatment-refractory colorectal cancer as monotherapy and incombination with irinotecan.

Phase 1 and Phase 2 clinical trials in multiple cancer types to datehave shown that Pexa-Vec, delivered either directly into tumors orintravenously, induces tumor shrinkage and/or necrosis and iswell-tolerated (over 200 patients treated to date). Objective tumorresponses have been demonstrated in a variety of cancers includingliver, colon, kidney, lung cancer and melanoma. Pexa-Vec has had apredictable and manageable safety profile to date which includesflu-like symptoms that resolve in 24 to 48 hours.

Pexa-Vec is the lead product candidate from Jennerex' SOLVE(TM)platform, a groundbreaking approach offering new therapeutic optionsfor patients with life-threatening cancers. SOLVE builds on thenatural attributes of vaccinia viruses to engineer highly targeted,oncolytic immunotherapies for cancer with minimal side effects.

About Jennerex's Regional Partners for Pexa-Vec Transgene (nyseeuronext paris:FR0005175080), a bio-pharmaceutical companyspecialized in the development of immunotherapeutic products, holdsan exclusive license to develop and commercialize Pexa-Vec in Europeand neighboring countries. Green Cross Corporation, a leading companyin the development, manufacturing, and commercialization of viralvaccines and other biological products, holds an exclusive license todevelop and commercialize Pexa-Vec in South Korea, and Lee'sPharmaceutical Ltd. holds an exclusive license to develop andcommercialize Pexa-Vec in China.

Transgene, a member of the Institut Merieux Group, is a publiclytraded French biopharmaceutical company dedicated to the developmentof therapeutic vaccines and immunotherapeutic products in oncologyand infectious diseases. Transgene has four compounds in phase 2clinical development: TG4010 and Pexa-Vec (TG6006) having alreadycompleted initial phase 2 trials, TG4001 and TG4040. Transgene hasconcluded three strategic agreements for the development of itsimmunotherapy products: an option agreement with Novartis for thedevelopment of TG4010 to treat various cancers; an in-licensingagreement with US-based Jennerex, Inc. to develop and market Pexa-Vec(TG6006), an oncolytic virus, and with the EORTC for the developmentof TG4001 to treat HPV induced head and neck cancers. Transgene hasbio-manufacturing capacities for viral-based products. Additionalinformation about Transgene is available at www.transgene.fr.

Green Cross Corp. is a publicly traded and leading Koreanbiopharmaceutical company specialized in development andcommercialization of vaccines, plasma-derivatives, recombinantproteins and therapeutic antibodies in oncology and infectiousdiseases. Green Cross Corp. has been collaborating with Jennerex inKorea since 2006 to jointly conduct the Phase 1 and 2 clinical trialsin patients with liver cancer. Additional information about GreenCross Corp. is available on the internet at www.greencross.com.

Lee's Pharmaceutical Holdings Limited is a research-basedbiopharmaceutical company listed in Hong Kong with over 19 yearsoperation in China's pharmaceutical industry. It is fully integratedwith strong infrastructures in drug development, manufacturing, salesand marketing. It has established extensive partnership with over 20international companies and currently has 14 products in the marketplace. Lee's focuses on several key disease areas such ascardiovascular, oncology, gynecology, dermatology and ophthalmology.Lee's development program is lauded with 30 products stemming fromboth internal R&D efforts and collaborations with US, European andJapanese companies and aspiring to combat diseases such as livercancer and pulmonary hypertension. The mission of Lee's is to becomea successful biopharmaceutical group in Asia providing innovativeproducts to fight diseases and improve health and quality of life.Additional information about Lee's Pharmaceutical is available atwww.leespharm.com.

About Jennerex Jennerex, Inc. is a clinical-stage biotherapeuticscompany focused on the development and commercialization ofbest-in-class, breakthrough targeted oncolytic immunotherapy productsfor cancer. The Company is focused on two main programs, lead productcandidate, Pexa-Vec (JX-594), which is in mid-stage clinicaldevelopment for the treatment of advanced primary liver cancer andcolorectal cancer and JX-929 which is under investigation for avariety of solid tumors. Jennerex is headquartered in San Franciscoand has related research and development operations in Ottawa, Canadaand Busan, South Korea. For more information about Jennerex, pleasevisit www.jennerex.com.

Media Contact:
Nicole Foderaro
BrewLife
415-946-1058
Email Contact

SOURCE: Jennerex

Thursday, January 31, 2013

Liver Cancer-Phase III HEAT trial of Thermodox Fails to Meet Goals

Investment Commentary

Celsion Liver Cancer Trial Fails to Meet Goals, Stock Plunges
Catherine Arnst1

In a major setback, Celsion (NASDAQ: CLSN), based in Lawrenceville, NJ, reported today that its lead drug candidate failed in a Phase III clinical trial for treatment of primary liver cancer. CEO Michael Tardugno told an investor conference call this morning that the result “was not even close” to meeting the trial’s goals.

Investor reaction was swift and furious, with Celsion’s share price dropping 80 percent in the first hour of trading, to $1.59 from the previous close of $8.02. Celsion’s stock had more than tripled in price over the prior year.

Celsion said that the Phase III HEAT trial of Thermodox—a proprietary reformulation of the chemo drug doxorubicin—in combination with radiation was designed to slow the cancer from spreading, a measure called progression free survival, by at least 33 percent compared with the control arm, but did not meet that goal. The trial results, Tardugno said, would not justify filing for approval in any country.

Part of the problem, Tardugno said, is that patients in the control arm did about 20 percent better on standard treatment than the company had projected. Cancer trials can sometimes take years to enroll patients and compile results from the time the trial design was approved, and during that time the standard of care continues to improve, making it more difficult for new treatments to show an advantage over existing therapies.

Celsion will continue to study the results to determine whether patients currently on Thermodox would be followed to determine whether the drug can extend overall survival.

The results were released just a week after the company announced a technology development deal for Thermodox in liver cancer with Zhejiang Hisun Pharmaceutical, a major Chinese drug company, that could have been worth up to $100 million over 10 years if the drug had succeeded. Celsion has already received an initial payment of $5 million from Hsuin, which Tardugno said the company is not required to give back the payment in light of the trial failure.

Tardugno sought to reassure investors by telling them the company has approximately $27 million in cash on hand as of today, enough money to fund its operations “well into 2014.”

Celsion’s drug technology, developed in partnership with Duke University, encases chemotherapy drugs in tiny bubbles called liposomes that are then activated by low levels of radiation to deliver their payload directly to cancer cells. Thermodox won fast-track designation from the Food & Drug Administration in August 2010 for development against primary liver cancer.

Celsion also has heat activated liposomes in Phase II clinical trials for breast cancer and a second form of liver cancer, but Tardugno said the company will have to give the latter trial “some consideration” before it decides whether or not to continue in light of the HEAT failure.

http://www.xconomy.com/new-york/2013/01/31/celsion-liver-cancer-trial-fails-to-meet-goals-stock-plunges/

Celsion plunges 80 percent as liver cancer therapy fails trial

Jan 31, 2013 11:36am EST
(Reuters) - Celsion Corp shares plunged by more than 80 percent after a late-stage study of the company's experimental liver cancer treatment ThermoDox failed to meet the main goal of increasing patients' survival without worsening their cancer.

The stock fell to a low of $1.41 before recovering slightly to trade at $1.46 on heavy volume on the Nasdaq on Thursday.

"I don't believe the data will support (marketing) registration in any of the major markets," Celsion Chief Executive Michael Tardugno said on a conference call.

The trial, named HEAT, consisted of 701 patients across 11 countries and was designed to show a 33 percent improvement in progression-free survival.

Celsion said it was conducting additional analyses of data from the trial to assess the future value of ThermoDox.

Patients on the control arm performed about 20 percent better than expected whereas those on ThermoDox performed worse than anticipated, Roth Capital Partners analyst Joseph Pantginis said, quoting the company.

"We are disappointed by the failure of the HEAT study and we highlight the increased risk around the company's pipeline which is driven by ThermoDox," he said.

ThermoDox is also being tested in mid-stage studies as a drug-delivery method for breast and colorectal cancers.

Celsion CEO Tardugno said the company will continue enrolling patients in the mid-stage breast cancer study.

ThermoDox utilizes a liposome -- a tiny bubble composed of lipids -- as a vehicle to transport a commonly used chemotherapy drug called doxorubicin, directly to the tumor.
Localized heat releases doxorubicin, depositing it in and around the tumor, maximizing the effect of the medication.

The liver-cancer study compared the HEAT results against patients treated with a procedure where tumors are destroyed using electricity, otherwise called radiofrequency ablation.
Pantginis downgraded Celsion's rating to "neutral" from "buy" and slashed his price target on the stock to $1.70 from $10, saying the target is now based solely on the mid-stage study of ThermoDox in breast cancer.

Celsion said it had sufficient cash to cover its expenses well into 2014. It has unaudited cash and investments of about $27 million.

CEO Tardugno said the company will review its colorectal cancer trial in the context of the HEAT results and then decide on whether to continue with the study.

(Reporting By Pallavi Ail in Bangalore; Editing by Roshni Menon and Sreejiraj Eluvangal)

http://www.reuters.com/article/2013/01/31/us-celsion-study-thermodox-idUSBRE90U0MI20130131

Tuesday, January 29, 2013

No Added Benefit for Chemo Beads in Liver Cancer

No Added Benefit for Chemo Beads in Liver Cancer

By Charles Bankhead, Staff Writer, MedPage Today
Published: January 28, 2013

Reviewed by F. Perry Wilson, MD, MSCE; Instructor of Medicine, Perelman School of Medicine at the University of Pennsylvania

SAN FRANCISCO -- Outcomes in hepatocellular carcinoma (HCC) failed to improve after hepatic arterial embolization (HAE) with doxorubicin-eluting beads (LC Bead) versus beads without the drug (Bead Block), a randomized trial showed.

Patients treated with drug-free beads had an overall response rate of 11% compared with 6% of patients who received the drug-eluting beads. About 85% of patients in both arms had stable disease, reported Karen Brown, MD, reported Memorial Sloan-Kettering Cancer Center in New York City, and colleagues.

Progression-free survival (PFS) was slightly better with the beads alone, and HAE with the doxorubicin-containing beads led to a nonsignificant 3-month increase in overall survival (OS), said Brown at the Gastrointestinal Cancers Symposium.

"Doxorubicin-loaded drug-eluting beads did not improve response rate, median time to progression, progression-free survival, or overall survival in this randomized trial," she explained. "The addition of doxorubicin to the beads does not appear to increase toxicity or compromise safety."
"This study brings into question the added benefit of chemotherapy for embolization of hepatocellular carcinoma," she added.

HAE has established a role in the treatment of HCC, but chemoembolization has garnered more support among clinicians, largely without a complete understanding of the role chemotherapy might play in HAE.

Two studies published about a decade ago have provided the evidentiary basis for chemoembolization, Brown said. In particular, one study showed superior 1- and 2-year survival with chemoembolization versus embolization and conservative treatment in patients with unresectable HCC (Lancet 2002; 359: 1734-1739).

"There was a sequential design of the study that allowed for termination when there was a significant survival benefit demonstrated in either of the study arms [versus conservative care]," said Brown. "This occurred earlier in the transarterial chemoembolization group, so when the survival benefit was demonstrated in that group, the study was stopped."

She pointed out the the authors of that study acknowledged that there were not enough patients in the embolization group to draw definitive conclusions. "Nonetheless, over 10 years later, many people interpret this study as showing a survival benefit for transarterial chemoembolization compared with either embolization or best supportive care, which is not the case," she said.

Continuing with a comparative evaluation of the two HAE strategies, Brown's group recruited patients with Okuda stage I-II unresectable HCC and randomized them to embolization or to chemoembolization with beads containing 150 mg of doxorubicin.

The primary endpoint was objective response rate by RECIST criteria as determined from multiphase CT imaging performed 3 weeks after treatment. Disease progression or ≤5% tumor necrosis was considered treatment failure.

Secondary objectives included safety and tolerability, time to progression (TTP), PFS, OS, and an exploratory comparison of response and other outcomes between the two groups.

Data analysis included 92 patients. Brown reported five partial responses (11%) in the embolization group and three (6%) in the chemoembolization arm. Additionally, 40 (87%) patients in the embolization group had stable disease, as did 39 (85%) patients in the chemoembolization group.
Investigators also evaluated response by lesion, using European Association for Study of the Liver criteria. The analysis included 171 lesions. The results showed a 100% decrease in 58% of lesions with embolization versus 61% of lesions treated with chemoembolization.

The proportion of lesions that decreased in size by more than 50% were 24% with embolization and 27% with chemoembolization, and 17% versus 11% of lesions in the respective groups decreased by less than 50%. One lesion in each group increased in size by more than 20%.

Analysis of secondary endpoints showed no significant differences between the groups:
  • 2-year probability TTP: 42% with embolization versus 49% with chemoembolization
  • 2-year probability PFS: 11% versus 19%
  • PFS: 5.2 months versus 4.6 months
  • OS: 16.6 versus 19.6 months
There was no difference in adverse events at 84% in both groups. The most common adverse event was postembolization syndrome of pain, fever, nausea, or vomiting.

Given current epidemiologic trends in HCC, the results have clear implications for management of the disease, said Françoise Mornex, MD, PhD, of Lyon University Hospital in France.

"The incidence of HCC is increasing everywhere in the world, so we need to find the best treatments and we need to optimize treatment," said Mornex, who was not involved in the study. "There are several methods to embolize and treat these patients, and we still don't know which is the best one, so this question is important, and these results in 100 patients are quite robust."

But she cautioned that questions still remain. "Should we reproduce these results with a larger cohort of patients? Should we believe in these results and change our practice directions? I'm not sure we should change our practice on the basis of one study, even if the study is very important," Mornex said.

Clinicians should consider the results and how they might fit into their own practice and then integrate the information as appropriate, she added.

Primary source: Gastrointestinal Cancers Symposium
Source reference:
Brown KT, et al "A randomized, single-blind, controlled trial of beads versus doxorubicin-eluting beads for arterial embolization of hepatocellular carcinoma (HCC)" GiCS 2013; Abstract 143.

http://www.medpagetoday.com/MeetingCoverage/MGICS/37038

Tuesday, January 1, 2013

Paired CT Scans Catch Chemo-Killing of Liver Tumors in Real Time


Paired CT scans catch chemo-killing of liver tumors in real time

Immediate feedback shows if chemotherapy worked, or if additional treatment is needed

Using two successive pairs of specialized CT scans, a team of Johns Hopkins and Dutch radiologists has produced real-time images of liver tumors dying from direct injection of anticancer drugs into the tumors and their surrounding blood vessels. Within a minute, the images showed whether the targeted chemotherapy did or did not choke off the tumors' blood supply and saved patients a month of worry about whether the treatment, known as chemoembolization, was working or not, and whether repeat or more powerful treatments were needed.

CT scans of a liver tumor before and after chemoembolization.
Specialized DPCBCT scans of a liver tumor in a 73 year old man before and after chemoembolization (second and fourth column from left) match up closely with MRI scans taken over a month later (first and third columns).

The Johns Hopkins team's report about this novel use of dual-phase cone-bean computed tomography, or DPCBCT, an imaging technique developed at Johns Hopkins, is set to appear in the January 2013 edition of the journal Radiology. The diagnostic scans were performed on 27 men and women with inoperable liver cancer.

"This new scanning method is giving us almost instant feedback about the value of injecting antitumor drugs directly into large liver tumors and their surrounding blood vessels in an effort to quickly kill them, and to prevent the cancer from spreading," says senior study investigator and interventional radiologist Jean-Francois Geschwind, M.D.

Geschwind says if further testing proves equally successful, the paired use of cone-beam CT scans, which are already approved for single-scan use by the U.S. Food and Drug Administration, could supplant the current practice of MRI scanning a month after chemoembolization to check its effects.
"Patients should not have to endure the uncertainty of waiting weeks or more to find out if their chemoembolization was successful in fighting their liver cancer," says Geschwind, a professor in the Russell H. Morgan Department of Radiology at the Johns Hopkins University School of Medicine and its Kimmel Cancer Center.

"Dual-phase cone-beam CT avoids such delays, which also could allow the cancer to grow and spread and, ultimately, compromise chances of remission," he says.

Avoiding delays is particularly important, he says, for people with moderate to advanced stages of the disease, when liver tumors are too large or too numerous to surgically remove, and for whom chemoembolization is the main treatment option. Half of such liver cancer patients succumb within nine months, and liver transplantation is only an option for a quarter of those whose tumors have not spread outside the liver.

The newer DPCBCT scans, in which X-rays are detected by a device the size of a large laptop that can be placed directly below or above the operating room table, have the added advantage of being performed in the same room, or interventional radiology suite, as patients getting chemoembolization.

In their new study, Geschwind and his colleagues found that the initial shrinkage seen with DPCBCT scans taken before and after chemoembolization matched up almost perfectly with MRI scans taken a month later. Tumor death was 95 percent, the same as that seen by MRI. A total of 47 tumors were closely monitored in the study to assess how well DPCBCT tracked tumor death after chemoembolization.  All study participants were treated at The Johns Hopkins Hospital between March and December 2009.

In DPCBCT scanning, a chemical contrast dye is injected into the artery that supplies blood flow to the liver and tumor right before the chemotherapy drug is injected, to enhance the X-ray image. The first set of scans highlights key blood vessels feeding the tumor, as dye flows in and out of the tumor. The second set of scans is performed immediately after chemoembolization, to gauge tumor and key blood vessel death. Computer software is used to sharpen and analyze differences between the images.

The entire DPCBCT scanning time, researchers say, is between 20 seconds and 30 seconds, and the total amount of radiation exposure from the dual scanning averages 3.08 milliseiverts, which is less than half the amount of radiation involved in a modern abdominal 64-CT scan. Cone-beam CT scanners also emit an X-ray, but unlike other CT scanners, the cone-beam type of X-ray is projected onto one large, rectangular detector, roughly a foot and a half long -- and produces a telltale conical shape. The size of the cone-beam CT detector allows for single scans that can capture images the size of most people's entire liver. More powerful 64-CT and 320-CT scanners involve multiple detector rows.

Chemoembolization entails the use of tiny beads containing the chemotherapy drug doxorubicin injected directly into liver tumors.  Ultrathin catheters, about the width of a human hair, are threaded through blood vessels to deliver the drugs, which seep from the beads for several weeks.

Geschwind is leading clinical trials under way at Johns Hopkins and other centers to assess whether the combination drug treatment works for liver cancer patients. Early results have shown promise, with patients with advanced disease living 10 months to 15 months longer.

Geschwind says they plan improvements in image quality in DPCBCT scans, hoping further refinements will encourage physicians to adopt the technique. They also plan updates to the navigational software that, like GPS, can track blood vessels feeding each tumor, and provide more precise and greater numbers of targets.
###
Liver cancer kills nearly 20,000 Americans each year, and is much more prevalent outside the United States, where it is among the top three causes of cancer death in the world. Experts cite the rising numbers of hepatitis C infections, which cause chronic liver inflammation and are a leading risk factor for liver cancer.

Funding support for this study was provided by the French Society of Radiology and Philips Research North America in Briarcliff Manor, N.Y. Philips, whose parent company is based in the Netherlands, manufactures the CBCT device used in the study. Additional funding support was provided by the U.S. National Cancer Institute, a member of the National Institutes of Health. The corresponding grant numbers are NCI R01-CA160771 and UL1 RR-025005.

The study lead investigators were Romaric Loffroy, M.D., a radiology fellow at Johns Hopkins, and MingDe Lin, Ph.D., a Philips biomedical engineer based at Johns Hopkins who has been collaborating with Geschwind for the past five years to perfect the DPCBCT technique.
In addition to Geschwind, Loffroy and Lin, other Johns Hopkins researchers involved in this research were Gayane Yenokyan, Ph.D., at the university's Bloomberg School of Public Health; and Pramod Rao, M.D.; Nikhil Bhagat, M.D.; and Eleni Liapi, M.D., all at the School of Medicine. Philips investigators involved were Niels Noordhoek, Ph.D.; Alessandro Radaelli, Ph.D.; and Jarl Blijd, M.Sc.

The chemoembolization research study was funded by Bayer HealthCare and Onyx Pharmaceuticals, manufacturer of sorafenib, and Biocompatibles, makers of the microbeads. Geschwind is a consultant to Bayer HealthCare Pharmaceuticals, and to Biocompatibles. The terms of these arrangements are being managed by The Johns Hopkins University in accordance with its conflict-of-interest policies.

Photos of DPCBCT scans can be found online at:
http://www.hopkinsmedicine.org

For additional information, go to:
http://radiology.rsna.org/content/early/2012/11/05/radiol.12112316.short?rss=1
http://www.hopkinsmedicine.org/vascular/staff/physicians/geschwind.html
http://www.hopkinsmedicine.org/vascular/procedures/chemoembolization/

Wednesday, August 8, 2012

Delcath Is About To Change The Way We Treat Liver Cancer

Investment commentary:

Delcath Is About To Change The Way We Treat Liver Cancer

By Icarus Falling @ Seeking Alpha

Delcath Systems, Inc. (DCTH) is a development stage, specialty pharmaceutical and medical device company focused on oncology. Delcath's proprietary system for chemosaturation is designed to administer high dose chemotherapy and other therapeutic agents to diseased organs or regions of the body, while controlling the systemic exposure of those agents, through the CHEMOSAT® delivery system. The company's initial focus is on the treatment of primary and metastatic liver cancers. With 700,000 people per year diagnosed with liver cancer worldwide, the market is robust.

The company is already marketing and selling the CHEMOSAT® delivery system in Europe.

The CHEMOSAT® delivery system allows the administration of concentrated regional chemotherapy by isolating the circulatory system of the targeted organ. Once the organ is isolated, the CHEMOSAT® delivery system delivers high doses of chemotherapeutic agents directly to the liver, while limiting systemic exposure and the related side effects by filtering the blood prior to returning it to the patient. The procedure is minimally invasive and repeatable allowing for multiple courses of treatment with chemotherapeutic drugs and the potential for concomitant cancer therapies.

Basically, the patient gets a more effective dose of chemotherapy and less of the devastating side effects. Can you think of any liver cancer patient that would not want to use the CHEMOSAT® delivery system?

The company just released earnings on August 7, 2012. On the conference call, the CEO confirmed that the company is finalizing its NDA submission to the FDA for the CHEMOSAT® delivery system and that the filing should be complete by mid-August. Specifically in the press release announcing the quarter results, it stated:

In the U.S., our New Drug Application (NDA) is on schedule and we expect to submit the file to the FDA by mid-August," continued Mr. Hobbs. "Our amendments to our Investigational New Drug (IND) application to include Generation 2 in our Expanded Access Program and all future clinical trials and compassionate use cases were accepted by the FDA. Additionally, after consultation with the FDA, we have agreed to include the addition of Generation 2 in our NDA submission as a technical change to the Chemistry, Manufacturing, and Control module.

More importantly, after the NDA is submitted, the company has announced that it will be able to decrease its monthly cash burn to between $3 and $4 million per month. With approximately $30 million in the bank, another $20 million revolving credit facility and $31 million available through an at the market equity facility, the Company should have sufficient capital to see the CHEMOSAT® delivery system approved by the FDA. While an equity raise at that point is likely, that is not abnormal in the biotech field, just look no further than Arena (ARNA) raising capital 1 month before the FDA approval of its weight loss drug.

At this point, the only reasons the stock is stuck below $2.00 is lack of faith in management and the open ATM of $31 million and fear of future dilution. I believe these fears to be overblown and now is the time to take a long position in Delcath and reap the rewards.

There will be bumps along the way, but at $1.70 per share, the upside is too hard to ignore. The 4 analysts covering the stock all maintain a buy rating on the stock and have an average price target of $7.67. Simply rising to 50% of the average analyst price target would allow anyone purchasing at these levels to double their money.

With commercialization in Europe already started, United States approval expected early next year, and continued worldwide rollout over the course of the next few years, Delcath appears to have put its troubles behind it and will be making the transition from a development stage company to a commercial enterprise.

Disclosure: I am long DCTH, ARNA.

Additional disclosure: Nothing contained herein shall constitute financial, investment, legal and/or other professional advice. Investors buy and sell securities at their own risk. I am currently long the two stocks mentioned in this article and as of this writing intend to hold these stocks until I see a significant return. I reserve the right to alter my planned investment decisions based upon a change in circumstances.

http://seekingalpha.com/article/791401-delcath-is-about-to-change-the-way-we-treat-liver-cancer

Monday, July 23, 2012

Combination of Tarceva, Nexavar fails to meet main goal of Phase III liver cancer study

July 23, 2012
Combination of Tarceva, Nexavar fails to meet main goal of Phase III liver cancer study
Last Updated:July 23, 2012 07:36

Bayer, Onyx Pharmaceuticals and Astellas announced Monday that a late-stage trial investigating the combination of Tarceva (erlotinib) and Nexavar (sorafenib) failed to meet the main goal of a late-stage trial in patients with unresectable hepatocellular carcinoma (HCC). "The data from SEARCH showed that the addition of Tarceva to Nexavar did not provide additional benefit to patients with unresectable HCC," remarked Dimitris Voliotis, vice president of global clinical development oncology at Bayer.

The SEARCH study randomised 720 patients with advanced liver cancer to receive treatment with Nexavar twice daily, either in combination with Tarceva once daily or placebo. Results demonstrated that the addition of Tarceva to Nexavar did not improve overall survival compared to Nexavar alone. The companies noted that data from the trial will be presented at a future medical meeting.

Nexavar, which is being jointly developed by Bayer and Onyx, is approved in the US and other countries for the treatment of patients with unresectable HCC and for the treatment of patients with advanced renal cell carcinoma. Tarceva is used to treat lung cancer and is co-marketed by Astellas and Roche's Genentech unit.

Analysts at Cheuvreux said the study results were a small negative for Bayer, but they left peak sales forecasts for Nexavar unchanged at 971 million euros ($1.2 billion) in 2019. Meanwhile, a spokesman for Roche noted while the company provided financial support as well as Tarceva for the trial, it did not have a development plan for the drug in liver cancer, either alone or as part of a combination.

Reference Articles
Bayer says Nexavar-Tarceva trial unsuccessful - (CNBC)
Bayer Says Phase III Tarceva-Nexavar Study Fails - (FinanzNachrichten)
Bayer Says Phase III Tarceva-Nexavar Study Fails - (NASDAQ)
Addition of Tarceva (erlotinib) to Nexavar (sorafenib) did not Provide Additional Benefit to Patients with Unresectable Liver Cancer Versus Nexavar alone in Phase 3 Trial - (PR Newswire)

Source - http://www.firstwordplus.com/Fws.do?src=corp_site&articleid=3BC42477F6134983B32824385309019C

Thursday, July 19, 2012

Hepatocellular carcinoma - Brivanib Phase III Does Not Meet Overall Survival Primary Endpoint


July 19, 2012 04:30 PM Eastern Daylight Time

BRISK-FL Study with Investigational Compound Brivanib in Hepatocellular Carcinoma Does Not Meet Overall Survival Primary Endpoint 


PRINCETON, N.J.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE: BMY) today reported the result of the phase III BRISK-FL clinical trial of the investigational agent brivanib versus sorafenib as first-line treatment in patients with advanced hepatocellular carcinoma (HCC; liver cancer). The study did not meet its primary overall survival objective based upon a non-inferiority statistical design.

BRISK-FL is a randomized, double-blind, multi-center phase III study of the investigational agent brivanib versus sorafenib in patients with advanced HCC who have not received prior systemic treatment. Bristol-Myers Squibb and the lead investigators plan to present the findings of the study at an upcoming scientific meeting.

“The treatment options for patients with advanced hepatocellular carcinoma are limited, and we are disappointed that the primary endpoint was not met,” said Brian Daniels, M.D., senior vice president, Global Development and Medical Affairs, Bristol-Myers Squibb. “Bristol-Myers Squibb remains committed to developing medicines for the treatment of diseases with serious unmet medical need, including diseases of the liver such as hepatitis C, hepatitis B, and liver cancer.”

Bristol-Myers Squibb is considering options for the ongoing brivanib development program. Ongoing clinical trials of brivanib, which include hepatocellular carcinoma as well as other tumor types, will continue at the present time. Additionally, Bristol-Myers Squibb shared the BRISK-FL results with the clinical trial investigators and will work with the investigators regarding the ongoing management of patients receiving study drug.

About Bristol-Myers Squibb’s Commitment to Liver Disease and Brivanib

Bristol-Myers Squibb is studying a portfolio of compounds that aim to address unmet medical needs across the liver disease continuum, including hepatitis C, hepatitis B and liver cancer. Brivanib is an investigational, oral, anti-tumorigenic that inhibits vascular endothelial growth factor receptor (VEGFR) and fibroblast growth factor receptors (FGFR).

Bristol-Myers Squibb Forward-Looking Statement

This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding product development. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among other risks, there can be no guarantee that the brivanib development program will be continued or, if the development program is continued, that it will support a regulatory filing or that brivanib will receive regulatory approval in any jurisdiction. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb's business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2011, in our Quarterly Reports on Form 10-Q and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information, please visit http://www.bms.com or follow us on Twitter at http://twitter.com/bmsnews.

Contacts 

Bristol-Myers Squibb Company
Media:
Cristi Barnett, 609-252-6028
cristi.barnett@bms.com
or
Investors:
John Elicker, 609-252-4611
john.elicker@bms.com 

Saturday, April 14, 2012

Tremelimumab Shows Promise in Patients With Liver Cancer

From Reuters Health Information > Conference News

Tremelimumab Shows Promise in Patients With Liver Cancer
By Fran Lowry

NEW YORK (Reuters Health) Apr 11 - Tremelimumab looked "promising" in a small phase II trial in patients with advanced hepatocellular carcinoma and hepatitis C, in some cases producing stable disease for more than a year, researchers said in Chicago earlier this month at the American Association for Cancer Research (AACR) Annual Meeting 2012.

Tremelimumab is a fully human monoclonal antibody that binds to CTLA-4 expressed on the surface of activated T lymphocytes, resulting in inhibition of B7-CTLA-4 mediated downregulation of T-cell activation, explained Dr. Ignacio Melero, from El Centro de Investigacion Medica Aplicada, Universidad de Navarra, in Pamplona, Spain.

"We had data that lymphocytes in liver infiltrates of hepatocellular carcinoma and chronic hepatitis C virus-infected patients expressed CTLA-4, which is the target of this monoclonal antibody," Dr. Melero told Reuters Health.

"In addition, there was previous experience in the potential immunogenicity of hepatocellular carcinoma cells. The most exciting point for us was that we could explore the effects on a tumor target and on a viral target at the same time," he said.

Dr. Melero and his group evaluated 20 patients who received tremelimumab, 15 mg/kg IV every 90 days for a median of two cycles (range, one to four). The median age was 68; 71% of the patients were male.

Two patients had a partial response, and 11 had stable disease. The duration of stable disease was more than 12 months in 33% of patients.

On intent-to-treat analysis, the median overall survival was 7.5 months and time to progression was 6.4 months, the researchers said in an April 2nd presentation at the conference.

Dr. Melero said the treatment was "globally very well tolerated." Eighty percent of the patients had drug-related adverse events, most frequently mild to moderate rash (40%), itching (45%), increased transaminase levels (30%), fatigue (20%) diarrhea (10%) constipation (10%) and anorexia (10%). No life-threatening adverse events occurred.

The researchers also observed a reduction of hepatitis C virus in patients' blood, and this was accompanied with enhanced antiviral immunity. The median values went from 3.78 x 10e5 copies/ml at baseline, to 3.02 x 10e4 copies/ml on day 120 (p=0.02), to 1.69 x 10e3 copies/ml on day 210 (p=0.04).

These decreases in viral load were associated with an increase in anti-hepatitis C virus immune response in 76% of the patients.

Dr. Melero said tremelimumab might also have potential for use in patients with chronic hepatitis C infection. There are hopes that it might prevent or delay the development of liver cancer.

"It is clear that treating hepatitis C virus in a patient with liver cancer is nonsense because the virus has already done its worst, but there is potential to complement therapies for HCV with anti-CTLA-4 monoclonal antibodies," he told Reuters Health.

Dr. Ruth He, from Georgetown Lombardi Comprehensive Cancer Center, Washington, DC, said it was still too early to make a definite conclusion from this small study. But, she told Reuters Health, "the compound should move forward for further evaluation. It is a unique compound because it deals with tumor immune tolerance. It's a totally new type of treatment."

The study was supported by Pfizer, and tremelimumab has been licensed by MedImmune.

Monday, April 2, 2012

Tremelimumab Shows Promise in Treatment of Liver Cancer

Tremelimumab Shows Promise in Treatment of Liver Cancer
April 2, 2012
  • Tumor burden reduction and disease stabilization occurred in some cases.
  • Tremelimumab also reduced blood levels of hepatitis C virus.
CHICAGO — Tremelimumab treatment stabilized patients with advanced hepatocellular carcinoma due to chronic hepatitis C infection for more than 12 months, according to data presented at the AACR Annual Meeting 2012, held here March 31 - April 4.

Researchers evaluated 21 patients treated with tremelimumab intravenously at a dose of 15 mg/kg every 90 days for about two cycles. Tumor burden was reduced for two patients, and disease stabilized for more than a year in 11 patients.

“The unique conditions [of heptaocellular carcinoma and hepatitis C infection] permitted us to monitor the antitumor effects and immune response to well-defined viral antigens, killing two birds with one stone,” said lead researcher Ignacio Melero, M.D., Ph.D., a consultant in the department of oncology and a professor and senior investigator in El Centro de Investigación Médica Aplicada at Universidad de Navarra in Pamplona, Spain.

In an intention-to-treat analysis, researchers observed a median overall survival of 7.5 months and time to progression of 6.4 months. They reported treatment-related adverse events among 80 percent of patients; grade 3 or higher adverse events included one case of pruritus, one case of purpura and five cases of elevated transaminases.

Melero and colleagues also observed a reduction of hepatitis C virus in the patients’ blood, which was also accompanied with objective enhancements of antiviral immunity.

“The short series of patients already showing clinical activity offers clear signs for the need to extend these trials,” Melero said. “It is unusual to spot clear signs of clinical activity with such a small number of patients, and the information on antiviral activity is also very promising.”

The study was supported by Pfizer, and tremelimumab has been licensed by MedImmune. Melero is a consultant for Bristol-Myers Squibb.

# # #

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About the AACR

Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR’s membership includes 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 18,000 attendees. In addition, the AACR publishes seven peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the Scientific Partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of individual and team science grants in cancer research that have the potential for patient benefit. The AACR actively communicates with legislators and policy makers about the value of cancer research and related biomedical science in saving lives from cancer.

For more information about the AACR, visit www.AACR.org.

Media Contact:
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Jeremy.Moore@aacr.org
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