Phase II colorectal cancer clinical trial first to receive support, scientific oversight from Van Andel Research Institute-Stand Up To Cancer Epigenetics Dream Team

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Jan 28, 2016, 10:30 ET

GRAND RAPIDS, Mich., Jan. 28, 2016 /PRNewswire/ -- The first clinical trial to move forward as part of the Van Andel Research Institute–Stand Up To Cancer (VARI–SU2C) Epigenetics Dream Team will target metastatic colorectal cancer, the second leading cause of cancer deaths among men and women combined in the U.S.

Nationally, an estimated 132,700 people were diagnosed with colorectal cancer in 2015, according to the U.S. Centers for Disease Control and Prevention. The high mortality rate is due in part to colorectal cancer's tendency to aggressively spread, or metastasize, to other organs. To better combat these metastatic cancers, scientists have turned to promising new epigenetic therapies that have potential to directly treat cancer or to sensitize tumors to traditional treatments.

"The first SU2C Epigenetics Dream Team made significant progress in treating some lung cancers, finding that epigenetics can potentially 'prime' cancer cells, making them more receptive to subsequent chemo and/or immunotherapy," said SU2C Co-founder Katie Couric. "I'm excited that the new VARI-SU2C Epigenetics Dream Team will work to build on those results, potentially bringing new hope to patients with colorectal cancer through this trial."

The trial is led by VARI–SU2C Epigenetics Dream Team members Nilofer Azad, M.D., and Nita Ahuja, M.D., at Johns Hopkins University's Sidney Kimmel Comprehensive Cancer Center, with scientific oversight and support provided by the Dream Team. Phase I has been underway since 2013; by conducting the next phase of the trial through the Dream Team, investigators will be able to add 40 more patients to phase II and perform additional specimen collection and analysis. These enhancements will provide a more thorough look into the efficacy of a potential new treatment for metastatic colorectal cancer.

"We're thrilled to support this promising trial as part of the VARI–SU2C Epigenetics Dream Team," said Peter Jones, Ph.D., D.Sc., Dream Team co-leader and VARI's research director. "Through this collaboration, we have an exceptional opportunity to further develop the next generation of epigenetic cancer therapies. The initial results from phase I were very encouraging and we look forward to the results of phase II."

The phase II trial will further test a combination therapy that includes a drug called guadecitabine (SGI-110), which corrects errors in methylation, a common epigenetic process that determines whether a gene is switched on or off. Genes that are inappropriately switched off do not produce proteins needed for normal function and can contribute to diseases such as cancer.

Phase II began enrolling patients in January. Although the trial is based at Johns Hopkins, clinical work will also occur at University of Southern California and Memorial Sloan Kettering Cancer Center – both Dream Team institutions – as well as VU University Medical Center in the Netherlands. Guadecitabine is supplied by Astex Pharmaceuticals, Inc.

Recent data suggest mutations in certain genes can be used to predict resistance to many common chemotherapies. Patients with these mutations are often first treated with a drug called irinotecan, followed by additional drug therapies if the cancer becomes desensitized to the initial treatment. Although first-line drugs like irinotecan are about 60 percent effective, efficacy for second and third line therapies drops to 10 percent and less than 5 percent, respectively. Ahuja's laboratory has shown that the use of demethylating drugs like guadecitabine can sensitize resistant colorectal cancer cell lines and tumors to irinotecan therapy. The team is now testing the hypothesis that the use of guadecitabine will re-sensitize patients to irinotecan, and allow for a better response and survival rate compared to current second and third line therapies.

"Being part of the VARI–SU2C Epigenetics Dream Team allows this exciting work to move forward quickly in patients," Azad said. "In particular, it allows us to test these drugs in enough patients to really have a strong sense if these drugs work for people with colorectal cancer."

Working through the Dream Team also allows investigators to gather additional samples from patients for further analysis, which will provide a deeper insight into colorectal cancer and metastasis.

"We're now able to collect additional biopsy tissues from the patients so that we can better understand how these therapies work using cutting-edge genomic studies," Ahuja said. "This kind of correlative work allows us to continuously improve our understanding of cancer."

The VARI–SU2C Epigenetics Dream Team was established in October 2014 and brings together scientists and clinicians from across the U.S. and abroad to move promising epigenetic therapies into clinical trials. Headquartered at VARI in Grand Rapids, Michigan, the VARI–SU2C Epigenetics Dream Team includes top scientists from five other leading institutions: Johns Hopkins University, Memorial Sloan Kettering Cancer Center, Temple University/Fox Chase Cancer, Rigshospitalet/ University of Copenhagen, and University of Southern California Norris Comprehensive Cancer Center, part of Keck Medicine of USC. The Dream Team receives objective scientific oversight from the American Association for Cancer Research (AACR).

TRIAL DETAILS:
Trial name: Phase I study of SGI–110 with irinotecan followed by randomized phase II study of SGI-110 with irinotecan versus regorafenib or TAS-102 in previously treated metastatic colorectal cancer

ClinicalTrials.gov number: NCT01896856

Principal investigator: Nilofer Azad, M.D., Sidney Kimmel Comprehensive Cancer Center

Co-principal investigator: Nita Ahuja, M.D., Sidney Kimmel Comprehensive Cancer Center

Patient totals: Phase I: up to 21. Phase II: 96. Total: 117

Industry partner: Astex Pharmaceuticals, Inc.

ABOUT VAN ANDEL RESEARCH INSTITUTE
Van Andel Institute (VAI) is an independent nonprofit biomedical research and science education organization committed to improving the health and enhancing the lives of current and future generations. Established by Jay and Betty Van Andel in 1996 in Grand Rapids, Michigan, VAI has grown into a premier research and educational institution that supports the work of more than 330 scientists, educators and staff. Van Andel Research Institute (VARI), VAI's research division, is dedicated to determining the epigenetic, genetic, molecular and cellular origins of cancer, Parkinson's and other diseases and translating those findings into effective therapies. The Institute's scientists work in onsite laboratories and participate in collaborative partnerships that span the globe. Learn more about Van Andel Institute or donate by visiting www.vai.org. 100% To Research, Discovery & Hope®

ABOUT STAND UP TO CANCER
Stand Up To Cancer (SU2C) raises funds to accelerate the pace of research to get new therapies to patients quickly and save lives now. SU2C, a program of the Entertainment Industry Foundation (EIF), a 501(c)(3) charitable organization, was established in 2008 by film and media leaders who utilize the industry's resources to engage the public in supporting a new, collaborative model of cancer research, and to increase awareness about progress being made in the fight against the disease. As SU2C's scientific partner, the American Association for Cancer Research (AACR) and a Scientific Advisory Committee led by Nobel Laureate Phillip A. Sharp, PhD, conduct rigorous, competitive review processes to identify the best research proposals to recommend for funding, oversee grants administration, and provide expert review of research progress.

Current members of the SU2C Council of Founders and Advisors (CFA) include Katie Couric, Sherry Lansing, Kathleen Lobb, Lisa Paulsen, Rusty Robertson, Sue Schwartz, Pamela Oas Williams, and Ellen Ziffren. All current members of the CFA were co-producers of the 2012 and 2014 televised specials. The late co-founder Laura Ziskin executive produced both the Sept. 5, 2008, and Sept. 10, 2010, broadcasts. SU2C was formally launched on May 27, 2008. Sung Poblete, PhD, RN, has served as SU2C's president and CEO since 2011.