July 22, 2016:

The Big Ten Cancer Research Consortium (Big Ten CRC) announces the opening of a Phase I/II clinical trial for advanced or metastatic hepatocellular carcinoma.

The study, known as BTCRC-GI13-002, will be conducted in two phases. In Phase I, researchers will determine the maximum safe dose of a drug called MLN0128. In Phase II, study participants will be randomized to one of two groups. One group will receive MLN0128 and the other will receive sorafenib, the standard therapy for patients with advanced or metastatic hepatocellular carcinoma.

MLN0128 is an investigational drug. This means it has not been approved by the U.S. Food and Drug Administration to treat any disease.

The Indiana University Melvin and Bren Simon Cancer Center in Indianapolis is currently enrolling participants in this study. Additional member sites within the Big Ten Cancer Research Consortium will open the trial in the coming months.

Bert H. O’Neil, MD, Joseph W. and Jackie J. Cusick Professor of Oncology at the Indiana University School of Medicine and a researcher at the IU Simon Cancer Center, is the sponsor investigator of the study.

“The patients we’re looking at have advanced disease, which means they’re not candidates for surgical therapy and they’re not candidates for transplants, which are the only curative therapies for this disease,” said O’Neil. “Currently, the standard of care for these patients is the drug sorafenib. This is an oral tyrosine kinase inhibitor that inhibits VEGF receptor kinases and other kinases. It’s a drug that does have efficacy in this population, but it’s fairly limited. This is an area where we need drugs with different mechanisms of action.”

MLN0128 is part of a class of drugs that targets the mTOR pathway. While an earlier study with the mTOR-targeting drug everolimus showed no improvement in overall survival for patients with advanced hepatocellular carcinoma, O’Neil believes this may be due in part to the way mTOR signaling works.

“mTOR actually is part of two different complexes — mTOR 1 and 2,” said O’Neil. “It turns out everolimus only inhibits mTOR 1. If you inhibit only mTOR 1 you actually get signaling through mTOR2 which can cause compensatory signaling through other pathways and may actually help the cancer. The drug we’re looking at is a new agent that targets both mTOR 1 and mTOR 2, the idea being that we can knock down the pathway without causing this compensatory signaling through the other pathway.”

O’Neil noted that MLN0128 has already shown activity in other cancers, including breast cancer and renal cell carcinoma. BTCRC-GI13-002 is the first study of MLN0128 in hepatocellular carcinoma.

Hepatocellular carcinoma is the most common type of primary liver cancer in adults. The National Cancer Institute estimates that more than 35,000 new cases of liver and intrahepatic bile duct cancer will be diagnosed in 2015 — about 2 percent of all new cancer diagnoses. The NCI reports that the rate of liver and intrahepatic bile duct cancers has been rising on average 4 percent each year for the past 10 years.

More information about this clinical trial, including full eligibility criteria, is available at www.clinicaltrials.gov, using trial #02575339.

About the Big Ten Cancer Research Consortium: The Big Ten Cancer Research Consortium was created in 2013 to transform the conduct of cancer research through collaborative, hypothesis-driven, highly translational oncology trials that leverage the scientific and clinical expertise of Big Ten universities. The goal of the Big Ten Cancer Research Consortium is to create a unique team-research culture to drive science rapidly from ideas to new approaches to cancer treatment. Within this innovative environment, today’s research leaders collaborate with and mentor the research leaders of tomorrow with the unified goal of improving the lives of all patients with cancer.

About the Big Ten Conference: The Big Ten Conference is an association of world-class universities whose member institutions share a common mission of research, graduate, professional and undergraduate teaching and public service. Founded in 1896, the Big Ten has sustained a comprehensive set of shared practices and policies that enforce the priority of academics in the lives of students competing in intercollegiate athletics and emphasize the values of integrity, fairness and competitiveness. The broad-based programs of the 14 Big Ten institutions will provide over $200 million in direct financial support to almost 9,500 students for more than 11,000 participation opportunities on 350 teams in 42 different sports. The Big Ten sponsors 28 official conference sports, 14 for men and 14 for women, including the addition of men’s ice hockey and men’s and women’s lacrosse since 2013. For more information, visit www.bigten.org.