Partnering for the Cure: Spotlight on Clinical Trials

Spotlight on Clinical Trials


Novel Therapeutic Trials for Patients with Hepatocellular Carcinoma


Sorafenib typically is used to treat patients newly diagnosed with hepatocellular carcinoma (HCC), a type of liver cancer that cannot easily be treated with surgery. Sorafenib is in a class of medications called protein kinase inhibitors that works by slowing the spread of cancer cells. However, for patients who do not respond to sorafenib, Ruth He, MD, of the Ruesch Center for the Cure of Gastrointestinal Cancers, and colleagues are about to open three clinical trials for this group of patients.

Eligible patients will be able to enroll in one of these trials based on the molecular (gene and protein) characteristics of their cancer.  Any patient interested in joining a trial should have a sample (biopsy) taken of their tumor, which will be analyzed for particular molecular traits in order to check for trial eligibility. Trial titles refer to the name of the new medication being studied in each case.

Trial 1 - Refametinib
Due to its rarity, the first HCC molecular variation we are looking for is a genetically altered KRAS gene (KRAS mutant), which accounts for only 5% of HCCs.  If a patient's tumor is classified as KRAS mutant, the patient will be invited to join a clinical trial where they will receive refametinib, another protein kinase inhibitor.  There is evidence to suggest that refametinib can be effective in inhibiting the growth of HCC, especially if the KRAS-mutation is also present.  Refametinib (also called Bay 86-9766) is an orally administered drug, which is not yet FDA-approved.

Trial 2 – Tivantinib
This trial is titled "A Phase 3, randomized, double-blind study of tivantinib in subjects with MET diagnostic-high inoperable HCC treated with one prior systemic therapy."  Tivantinib binds to the "c-Met" protein kinase—also known as hepatocyte growth factor receptor— and inhibits its growth communication pathways, thus leading to death of tumor cells that make too much and/or have especially active c-Met—termed as being "c-Met-positive".  Forty-five percent of patients have c-Met positive HCC and this group of patients will be invited to join this tivantinib trial.  Tivantinib (also called ARQ197) is an orally administered drug, which is not yet FDA-approved.

Trial 3 - Regorafenib
The first two trials described above encompass around 50% of HCC patients.  For the 50% of patients who do not possess these mutations in their tumor, a trial is available titled "A randomized double-blind, placebo-controlled, multi-center Phase III study of regorafenib in patients with HCC after sorafenib."  Regorafenib is an orally administered drug that has yet to be FDA-approved for HCC treatment. It binds to and obstructs chemical signals produced by cells that stimulate the growth of new blood vessels in tumor cells and promote tumor cell growth.  Patients joining this trial cannot have had previous treatment with regorafenib.

The Ruesch Center also has trials for patients who have already undergone more than one treatment for HCC, and are in a more advanced stage of the disease.

Please e-mail for more information.