SCOTTSDALE, Ariz. -- Oct. 3, 2019 -- Adding a drug that targets a molecular vulnerability in pancreatic cancer could provide substantial benefit to patients, according to a clinical trial study by the HonorHealth Research Institute and the Translational Genomics Research Institute (TGen), an affiliate of City of Hope, in conjunction with the Pancreatic Cancer Research Team and Cancer Research And Biostatistics.
Published today in the Journal of the American Medical Association (JAMA) Oncology, researchers found that among a clinical trial of 25 patients, adding the drug cisplatin to a current standard-of-care drug regimen resulted in substantial tumor shrinkage for 71 percent of those patients, and dramatically increased survival beyond one year.
"By adding the drug cisplatin to the current standard of care -- nab-paclitaxel plus gemcitabine -- we demonstrated substantial clinical activity. The results of this triple-drug regimen are very encouraging for these patients," said Daniel D. Von Hoff, M.D., FACP, who is physician-in-chief, distinguished professor and director of TGen's Molecular Medicine Division; and chief scientific officer at HonorHealth Research Institute and founder of the Pancreatic Cancer Research Team (PCRT). He also is leader of the Stand Up To Cancer (SU2C)-Cancer Research UK (CRUK)-Lustgarten Foundation Pancreatic Cancer Dream Team.
One year after entering the trial, 16 patients (64 percent) were still alive, far greater than the average one-year survival, which is only 26 percent for advanced pancreatic cancer patients. Ten patients (40 percent) were alive after two years, a survival rate not previously seen for patients with stage IV pancreatic cancer, said Dr. Von Hoff, the study's senior author.
"In addition to a high overall response rate, this three-drug combination was well tolerated, with manageable side effects," said Gayle Jameson, N.P., the principal investigator in this clinical trial and one of the study's co-lead authors.
The most significant side effects were a lowering of platelets, which helps blood clotting; lower levels of red blood cells, which carry oxygen throughout the body; and fewer neutrophils, the most common type of white blood cells, which serve as the immune system's primary defense against bacterial and viral infections.
Nearly two-thirds of patients in the clinical trial completed at least three 21-day, full-dose therapy cycles, Jameson said. Toxicity levels were minimized by using a relatively low dose of cisplatin and providing patients with aggressive intravenous hydration.
The combination of nab-paclitaxel and gemcitabine -- pioneered by a 2009 SU2C Pancreatic Cancer Dream Team, also supported by the Lustgarten Foundation and led by Dr. Von Hoff -- was approved by the FDA in 2013. Extensive testing led by HonorHealth and TGen demonstrated that the combination enabled longer survival for patients with advanced pancreatic cancer.
"Many pancreatic tumors possess DNA repair deficiencies and are potentially vulnerable to new targeted therapies. We hypothesized that the addition of a platinum, in this case cisplatin, could improve treatment efficacy and patient outcomes," said Erkut Borazanci, M.D., a clinical oncology investigator at HonorHealth Research Institute, and clinical associate professor at TGen. Dr. Borazanci also is a co-lead author of the paper and an investigator on the SU2C-CRUK-Lustgarten Dream Team.
In laboratory conditions, TGen researchers had discovered that cisplatin inhibited the ability of pancreatic cancer cells to repair their DNA, causing them to self-destruct.
Because some patients showed substantial improvement in the first three weeks of this clinical trial, this three-drug combination -- dubbed the "TGen Triple" or "Triplet regime" -- is being considered for early management of pancreatic cancer patients, and also as a pre-surgical treatment, according to the study.
"Considering the rapid disease response, acceptable safety profile, and encouraging anti-tumor activity, further study of this triple-drug combination and additional tumor molecular analysis is needed to correlate these molecular findings with patient response to treatment," Dr. Von Hoff said.
Professor Gerard Evan of Cambridge University, co-leader of the SU2C-CRUK-Lustgarten Dream Team, said,"Pancreatic cancer remains one of the hardest cancers to treat and too many people lose their lives to the disease each year. But these promising early results suggest that combining the common cancer drug cisplatin with standard treatments can significantly boost survival.
"We're now building on this work and investigating how to navigate the seemingly impenetrable structure of pancreatic tumors, which have a poor blood supply and reside in a dense web of tangled connective tissue that protects them from drugs. We're now developing new treatments designed to open up the tumors' blood supply make it easier for our drugs to reach every pancreatic cancer cell."
This treatment is being further studied by the HonorHealth Research Institute. The clinical trial is available to patients with untreated advanced pancreatic cancer. For more information, please go to HonorHealth.com/research or call 480-323-1339.
The team is studying this treatment in combination with the addition of super-enhancer modifying drugs such as entinostat, minnelide, high-dose pharmaceutical vitamin C, ketogenic diet and AXL inhibitors.
Contributing to this study -- High response rate in a phase Ib/II pilot trial with albumin-bound paclitaxel plus gemcitabine plus cisplatin in patients with advanced pancreatic cancer -- were: University of Arizona Comprehensive Cancer Center, Rutgers Cancer Institute, Vita Medical Associates, Mayo Clinic in Arizona, Imaging Endpoints Research and Core Lab and Cancer Research And Biostatistics, as the operations office and statistics and data management center for the Pancreatic Cancer Research Team.
This research is supported by a SU2C-CRUK-Lustgarten Pancreatic Cancer Dream Team research grant (SU2C-AACR-DT20-16). Additional funding was provided by: Roger E. Magowitz and the Seena Magowitz Foundation, the TGen Foundation, the HonorHealth Foundation and Mattress Firm.
About TGen, an affiliate of City of Hope
Translational Genomics Research Institute (TGen) is a Phoenix, Arizona-based non-profit organization dedicated to conducting groundbreaking research with life-changing results. TGen is affiliated with City of Hope, a world-renowned independent research and treatment center for cancer, diabetes and other life-threatening diseases: http://www.cityofhope.org. This precision medicine affiliation enables both institutes to complement each other in research and patient care, with City of Hope providing a significant clinical setting to advance scientific discoveries made by TGen. TGen is focused on helping patients with neurological disorders, cancer, diabetes and infectious diseases through cutting-edge translational research (the process of rapidly moving research toward patient benefit). TGen physicians and scientists work to unravel the genetic components of both common and complex rare diseases in adults and children. Working with collaborators in the scientific and medical communities worldwide, TGen makes a substantial contribution to help our patients through efficiency and effectiveness of the translational process. For more information, visit: http://www.tgen.org. Follow TGen on Facebook, LinkedIn and Twitter @TGen.
TGen Senior Science Writer
About HonorHealth and the HonorHealth Research Institute
HonorHealth is a nonprofit health system serving an area of 1.6 million people in the greater Phoenix area. The network encompasses five acute-care hospitals, an extensive medical group, outpatient surgery centers, a cancer care network, clinical research, medical education and community services. HonorHealth's mission is to improve the health and well-being of those we serve. Learn more at HonorHealth.com.
The HonorHealth Research Institute is helping shape the future of medicine. We're finding cures and improving treatments in areas like gene therapy, early drug and device development, and early detection and prevention of disease. Through our clinical trials and applied research, we've given hope and improved the lives of patients from all 50 states and 28 different countries around the globe. Our advanced technologies and cutting-edge treatment options are introducing tomorrow's cures, today. Find a clinical trial or learn more at HonorHealth.com/research.
About the Seena Magowitz Foundation
Founded in 2002, the Seena Magowitz Foundation is dedicated to bringing people, sponsors, organizations and medical research together in synergistic concert to fight pancreatic cancer. The foundation is uniquely focused on early detection, increasing survival rate, empowering people with awareness and eventually finding a cure. http://www.seenamagowitzfoundation.org
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 division of the Entertainment Industry Foundation, a 501(c)(3) charitable organization, was established in 2008 by media and entertainment leaders who utilize these communities' resources to engage the public in supporting a new, collaborative model of cancer research, to increase awareness about cancer prevention, and to highlight progress being made in the fight against the disease. As of June 2019, more than 1,600 scientists representing more than 180 institutions are involved in SU2C-funded research projects.
Under the direction of our Scientific Advisory Committee, led by Nobel laureate Phillip A. Sharp, Ph.D., SU2C operates rigorous competitive review processes to identify the best research proposals to recommend for funding, oversee grants administration, and ensure collaboration across research programs.
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. The late Laura Ziskin and the late Noreen Fraser are also co-founders. Sung Poblete, Ph.D., R.N., serves as SU2C's CEO. For more information, visit http://www.StandUpToCancer.org.
Jane E. Rubinstein
Sr. VP Communications
About Lustgarten Foundation
Lustgarten Foundation is the largest private funder of pancreatic cancer research in the world. Based in Woodbury, N.Y., the Foundation's mission is to cure pancreatic cancer by funding scientific and clinical research related to the diagnosis, treatment, and prevention of pancreatic cancer; providing research information and clinical support services to patients, caregivers and individuals at high risk; and increasing public awareness and hope for those dealing with this disease. Since its inception, Lustgarten Foundation has directed $186 million to research and has assembled the best scientific minds with the hope that one day, a cure can be found. Thanks to separate funding to support administrative expenses, 100% of your donation goes directly to pancreatic cancer research. For more information, visit http://www.lustgarten.org.
Social Media and PR Manager
About Cancer Research UK
* Cancer Research UK is the world's leading cancer charity dedicated to saving lives through research.
* Cancer Research UK's pioneering work into the prevention, diagnosis and treatment of cancer has helped save millions of lives.
* Cancer Research UK receives no funding from the UK government for its life-saving research. Every step it makes towards beating cancer relies on vital donations from the public.
* Cancer Research UK has been at the heart of the progress that has already seen survival in the UK double in the last 40 years.
* Today, 2 in 4 people survive their cancer for at least 10 years. Cancer Research UK's ambition is to accelerate progress so that by 2034, 3 in 4 people will survive their cancer for at least 10 years.
* Cancer Research UK supports research into all aspects of cancer through the work of over 4,000 scientists, doctors and nurses.
* Together with its partners and supporters, Cancer Research UK's vision is to bring forward the day when all cancers are cured.
For further information about Cancer Research UK's work or to find out how to support the charity, please call 0300 123 1022 or visit http://www.cancerresearchuk.org. Follow us on Twitter and Facebook.
About Stand Up To Cancer (UK)
* Stand Up To Cancer is a joint national fundraising campaign from Cancer Research UK and Channel 4 that brings the UK together to speed up progress in life-saving cancer research.
* Launched in the UK in 2012, Stand Up To Cancer funds translational research, turning academic breakthroughs in the labs into new treatments that make a real difference for people with cancer.
* More than £62 million has been raised in the UK to date, funding 52 clinical trials and projects involving 11,000 cancer patients across the country.
Research projects include the development of pioneering technology to detect super low levels of cancerous DNA in blood to improve the way we diagnose ovarian cancer, developing a new immunotherapy drug to boost the power of the immune system against cancer, exploring an entirely new approach to treating bowel cancer, and much more.
* Stars such as Naomi Campbell, Noel Gallagher, Tom Hardy, Gillian Anderson, Idris Elba, Andy Murray, James Corden, Martin Freeman, Jamie Oliver, Richard Ayoade, Chiwetel Ejiofor, Peter Crouch, Abbey Clancy, Danny Dyer, Liam Payne, Louis Tomlinson, Lily James, Rosamund Pike, Sophie Turner, Stephen Graham, Toby Jones, Maya Jama, Joe Lycett and Roman Kemp are just some of the talent who have supported Stand Up To Cancer.
* To find out more about Stand Up To Cancer and how you can support, visit Standuptocancer.org.uk or channel4.co.uk/SU2C or follow us on Facebook, Twitter or Instagram.
About Cancer Research And Biostatistics (CRAB) and Pancreatic Cancer Research Team (PCRT)
CRAB is a Seattle-based non-profit organization whose mission is to help conquer cancer and other diseases through the application of biostatistical principles and innovative data management methods. CRAB provides a complete suite of cancer clinical trial services including the design of therapeutic and prevention trials, customized electronic data capture platforms, data management and statistical services from clinical protocol design to final data analysis and presentation.
Founded by leaders in pancreatic cancer clinical research in 2003, the PCRT is a consortium of more than 40 clinics and leading research institutions worldwide, and serves as a premiere resource for the latest pancreatic cancer clinical trials. Acquired by CRAB in 2014, the PCRT provides a valuable collaborator for biotech and pharmaceutical companies looking to develop new agents or diagnostics for pancreatic cancer patients. This network provides the world's most coordinate effort dedicated to rapidly translating research discoveries into new treatments and care.