Phase II Trial Shows Overall Survival Benefit With VT-122 Plus Sorafenib in Advanced Hepatocellular Carcinoma

The gist: People with advanced hepatocellular carcinoma may benefit from treatment with a combination of the drugs VT-122 and sorafenib (Nexavar). That was the conclusion of a recent clinical trial—a research study with volunteer patients. The goal of the trial was to test the combination treatment. In the trial, people who took the combination had an 11-month increase in overall survival compared to people who took only sorafenib.

“The investigational agent VT-122 appeared to benefit survival when combined with sorafenib (Nexavar) in patients with advanced hepatocellular carcinoma, according to data presented at the 8th Annual International Liver Cancer Association Conference in Kyoto, Japan. Researchers reported an 11-month increase in median overall survival in patients treated with VT-122 plus sorafenib, compared to those receiving sorafenib alone.

“VT-122 is a novel, oral, chronodosed combination of the nonsteroidal anti-inflammatory drug (NSAID) etodolac and the beta-blocker propranolol. The investigational compound inhibits prostaglandin and beta-adrenergic signaling to reduce tumor-promoting inflammation and restore a tumor-suppressing immune state…

“In this phase II randomized, open-label, controlled clinical trial, 24 patients with advanced hepatocellular carcinoma were randomly assigned to receive VT-122 plus sorafenib or sorafenib alone.”


Trial Shows Improved Overall Survival for Patients with Liver Cancer not Amenable to Surgery

The gist: This article describes the results of a clinical trial—a research study with volunteer patients. The goal of the trial was to test a new treatment for people with inoperable advanced hepatocellular carcinoma (HCC). The new treatment combines two existing treatments: a chemotherapy drug called sorafenib and Selective Internal Radiation Therapy (SIRT). The results of the trial showed improved survival for the patients who participated. The new treatment will continue to be tested in the hopes that it may prove good enough to be widely used to treat advanced HCC.

“The mature results from a trial conducted by the Asia-Pacific Hepatocellular Carcinoma Trials Group led by the National Cancer Centre Singapore (NCCS) and Singapore General Hospital (SGH) have shown that patients who suffer from inoperable advanced hepatocellular carcinoma (HCC) may have a chance to live significantly longer by using a combined therapy.

“The multi-centre phase II clinical trial was conducted at four Asia Pacific tertiary medical centres to evaluate the efficacy of combining two existing treatment modalities, Sorafenib and Selective Internal Radiation Therapy (SIRT). The combination therapy involves starting patients on SIRT using SIR-Spheres microspheres, a medical device that contains radioactive microspheres labeled with yttrium-90 for short range high energy radiation therapy, followed by systemic therapy with an oral chemotherapy drug, Sorafenib, 14 days later.

“The mature results of the trial published recently in a peer-reviewed journal, PLOS ONE, show that median overall survival was 20.3 months for patients with intermediate stage HCC and 8.6 months for patients with advanced liver cancer. These final results were better than the preliminary data released in 2010.”


Celsion Announces Enrollment of First Patient in Global Phase III OPTIMA Study of ThermoDox® in Primary Liver Cancer

Editor’s note: This article is about a new clinical trial—a research study with volunteer patients. The goal of the trial is to test the effectiveness of a new liver cancer treatment. The treatment combines the drug ThermoDox with a procedure called radiofrequency ablation (AFA). It is meant for people with hepatocellular carcinoma (HCC). The trial has enrolled its first participating patient, and will enroll a total of 550 patients at sites in North America, Europe, China, and Asia Pacific.

“Celsion Corporation (NASDAQ: CLSN), an oncology drug development company, today announced that the first patient has been enrolled in its pivotal Phase III OPTIMA Study of ThermoDox® in combination with optimized radiofrequency ablation (RFA) in patients with primary liver cancer, also known as hepatocellular carcinoma (HCC).  ThermoDox® is Celsion’s proprietary, heat-activated, liposomal encapsulation of doxorubicin.

” ‘There is an urgent need for new treatment options that address primary liver cancer, a rapidly progressing disease with a poor prognosis whose worldwide incidence is growing at an alarming rate,’ stated Won-Young Tak, M.D., Ph.D. at the Kyungpook National University Hospital in South Korea and Asia Pacific Principal Investigator for the OPTIMA Study. ‘The OPTIMA Study builds on extensive clinical and preclinical data that point to the potential of ThermoDox®, when combined with an optimized RFA regimen, to significantly improve patient outcomes. I look forward to working with my colleagues to further explore the clinical utility of ThermoDox® in this setting.’ “


Veterans with NAFLD-Related HCC Lacked Surveillance Before Diagnosis

“Veterans with hepatocellular carcinoma related to nonalcoholic fatty liver disease underwent surveillance at a lower rate compared with veterans with hepatocellular carcinoma associated with hepatitis C virus or alcohol abuse, according to new study data.

“Researchers, including Sahil Mittal, MD, MS, assistant professor at Baylor College of Medicine, analyzed medical records from 1,500 patients (mean age at diagnosis, 63.7 years; 99.8% men) with hepatocellular carcinoma (HCC) from VA hospitals for fiscal-years 2005 to 2010. Eight percent of the cohort had nonalcoholic fatty liver disease (NAFLD); 80.6% showed alcohol abuse; 67.5% had hepatitis C virus (HCV); 4.6% had hepatitis B virus (HBV); and 61.8% displayed more than one risk factor. Most veterans with NAFLD-related HCC were older and white.”


Longer Wait to Liver Transplantation Associated with Reduced HCC Recurrence

“Risk for hepatocellular carcinoma recurrence after liver transplantation was lower among patients who waited more than 120 days from exception to transplantation compared with patients who did not in a recent study.

“John P. Roberts, MD; Mariya L. Samoylova; and colleagues from the department of surgery, University of California, San Francisco, analyzed data from 5,002 adult liver transplantation candidates from the United Network for Organ Sharing. All were granted initial exceptions because of hepatocellular carcinoma (HCC) diagnoses between January 2006 and September 2010. Patients waiting no more than 120 days for a transplant were compared with those waiting longer…

“When factoring in tumor quantity and size, ablative therapy and other factors, HCC recurrence risk was reduced by 40% in patients waiting longer than 120 days for transplantation (P=.005).

“ ‘This waiting period is to make sure that the tumor has not spread outside of the liver so that it would not be cured by liver transplantation,’ Roberts said. ‘We found that a waiting period of 120 days appears to decrease the risk of post-transplant recurrence.’ “


PCPs Commonly Fail to Offer HCC Screen to Patients with Cirrhosis

“Various primary care physicians in North Carolina who examine patients with cirrhosis do not offer a screening for hepatocellular carcinoma, according to results from a recent study.

“Researchers from the University of North Carolina, including Paul H. Hayashi, MD, MPH, used the North Carolina Medical Board database and mailed a letter and 12-item survey to 1,000 randomly assigned PCPs to address their knowledge of HCC surveillance and screening and whether they recommend it or perform it on their patients with cirrhosis. In all, 391 PCPs completed the survey and two were not included. Ninety percent of the 389 PCPs (n=345) saw patients with cirrhosis.”


Celsion Announces Updated Overall Survival Data from HEAT Study of ThermoDox® in Primary Liver Cancer

Editor’s note: Researchers conducted a clinical trial with volunteer patients to test the effectiveness of a liver cancer treatment called ThermoDox. Specifically, the trial looked at ThermoDox when given to hepatocellular carcinoma (HCC) patients in combination with radiofrequency ablation (RFA). The researchers found that patients who were treated with the combination survived longer than patients who were treated with RFA alone. 

” ‘As the data from the HEAT Study matures, it increasingly underscores the significant potential of ThermoDox® plus optimized RFA to markedly improve Overall Survival in primary liver cancer patients,’ stated Riccardo Lencioni, MD, FSIR, EBIR, Professor and Director of the Diagnostic Imaging and Intervention at the Pisa University School of Medicine in Italy.  ‘There is a pressing need for new treatment options to address HCC, which is a highly prevalent and deadly cancer. The consistency and strength of the HEAT Study data over each of the last five quarterly data analyses provide a strong rationale and clear roadmap for further development of ThermoDox® in this indication.’

“As of June 30, 2014, data from the latest HEAT Study post-hoc analysis continued to strongly suggest that ThermoDox® may significantly improve OS compared to a RFA control in patients whose lesions undergo RFA treatment for 45 minutes or more.  These findings apply to patients with single HCC lesions (64.4% of the HEAT Study population) from both size cohorts of the HEAT Study (3-5 cm and 5-7 cm) and represent a subgroup of 285 patients.  For this group, clinical results indicate a 57% improvement in OS, a Hazard Ratio of 0.639 (95% CI 0.419 – 0.974), and a p-value of 0.037.

” ‘The post-hoc HEAT Study data is striking in that it has consistently shown a marked OS benefit for ThermoDox® plus optimized RFA versus RFA alone in each of the quarterly data sweeps, with this 5th, and final data set demonstrating that this survival benefit is statistically significant,’ stated Michael Tardugno, Celsion’s President and Chief Executive Officer. ‘This impressive clinical data set, together with prospective supportive preclinical study results and multivariate Cox Regression Analyses, reinforces our confidence in the protocol for our Phase III OPTIMA Study in primary liver cancer, which is evaluating ThermoDox® in combination with a standardized RFA protocol in primary liver cancer.’ “


HCC Inhibitor Receives FDA Orphan Drug Designation

The gist: When a newly developed drug for a rare (“orphan”) disease seems particularly promising for patients, the U.S. Food and Drug Administration (FDA) may choose to grant it “orphan drug designation.” The designation removes certain barriers that might otherwise keep a drug company from being able to successfully develop and profit from the drug in the U.S. A new drug called ENDM-2076 has just received an orphan drug designation for the treatment of hepatocellular carcinoma (HCC).

“Casi Pharmaceuticals has received an orphan drug designation from the FDA for ENMD-2076 to treat hepatocellular carcinoma, according to a press release.

“With the status, Casi will be able to market ENMD-2076, an Aurora A/angiogenic kinase inhibitor, exclusively for 7 years, seek opportunities for additional funding and receive expert protocol assistance, according to the release.

“ ‘We are pleased with the orphan drug designation, as it confirms our belief in the versatility of ENMD-2076 as a promising treatment for HCC and for other tumor types that we are currently evaluating in the clinic,’ Ken K. Ren, PhD, chief executive officer of Casi Pharmaceuticals, said in the release. ‘Orphan drug status also enhances the commercial value of ENMD-2076 to treat HCC, a disease which is difficult to treat. We are finalizing our next steps for ENMD-2076 in HCC and/or in fibrolamellar carcinoma, a subset of HCC and for which there is no treatment available, and look forward to advancing our overall development plan for ENMD-2076.’ ”


Drug Everolimus Does Not Improve Overall Survival in Patients with Advanced Liver Cancer

“Despite strong preclinical data, the drug everolimus failed to improve overall survival in patients with advanced liver cancer, compared to placebo, according to a study in the July 2 issue of JAMA.

“Patients with advanced hepatocellular carcinoma (HCC; a type of liver cancer) have a median overall survival of less than l year, largely because of the absence of effective therapies. The drug sorafenib is the only systemic therapy shown to significantly improve overall survival in advanced HCC; however its benefits are mostly transient and modest, and disease eventually progresses. In preclinical models, everolimus prevented tumor progression and improved survival, according to background information in the article.

“Andrew X. Zhu, M.D., Ph.D., of the Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, and colleagues randomly assigned 546 adults with advanced HCC whose disease progressed during or after sorafenib or who were intolerant of sorafenib to receive everolimus (n = 362) or placebo (n = 184), both given in combination with best supportive care and continued until disease progression or intolerable toxicity. In this phase 3 study, patients were enrolled from 17 countries between May 2010 and March 2012.

“The researchers found no significant difference in overall survival between the two groups…”

Editor’s note: This article describes a clinical trial with volunteer patients to test a potential new liver cancer drug called everolimus. Patients in the trial all had advanced hepatocellular carcinoma (HCC) and had been unsuccessfully treated with sorafenib. Half were given everolimus, and for comparison, half were given a “fake” placebo drug. Unfortunately, there was no significant difference in survival between the two groups.