Clinical protocols for the treatment of gastrointestinal cancer

Greten, Tim

Abstract

Gastrointestinal cancer represent one of the major reasons for tumor related death in the United States. Current treatment options are limited to surgery, chemotherapy, radiation therapy and molecular targeted therapy and new treatment options are urgently needed. In 2017 we finished and published a number of clinical trials: 1.) We published our first study of combined ablation and immunotherapy using anti-CTLA4 in HCC. 2.) We published results from a clinical trial testing a vascular gaent (Trc105) plus sorafenib in patients with HCC. We are currently enrolling and or treating patients on the following trials: NCI-C0120: A Pilot Study of Tremelimumab - A Monoclonal Antibody against CTLA-4 in combination with Trans-Arterial Catheter Chemoembolization (TACE), Radiofrequency Ablation (RFA), Stereotactic Body Radiation Therapy (SBRT) or Cryoablation in Subjects with Hepatocellular Carcinoma (HCC) or Biliary Tract Carcinomas (BTC). Enrollement has currently been completed and we follow up patients. 15-C-0027: A Pilot Study of Immune Checkpoint Inhibition (Tremelimumab and/or MEDI4736) in Combination With Radiation Therapy in Patients With Unresectable Pancreatic Cancer. We are currently enrolling patients. 16C0135: A Pilot Study of Combined Immune Checkpoint Inhibition in combination with ablative therapies in Subjects with Hepatocellular Carcinoma (HCC) or Biliary Tract Carcinomas (BTC). Enrollment for this study has started a few months ago 17-C-0082: A Phase 2 Study of Pembrolizumab, a Monoclonal Antibody Against PD-1, in Combination with Capecitabine and Oxaliplatin (CAPOX) in Subjects with Advanced Biliary Tract Carcinoma (BTC). Enrollment has just started.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Cancer Institute (NCI)
• Type: Investigator-Initiated Intramural Research Projects (ZIA)
• Project #: 1ZIABC011343-08
• Application #: 9556536
• Support Year: 8
• Fiscal Year: 2017

Institution

• Name: Basic Sciences

Publications

Brown, Zachary J; Yu, Su Jong; Heinrich, Bernd et al. (2018) Indoleamine 2,3-dioxygenase provides adaptive resistance to immune checkpoint inhibitors in hepatocellular carcinoma. Cancer Immunol Immunother 67:1305-1315

Alter, Harvey; Block, Timothy; Brown, Nathaniel et al. (2018) A research agenda for curing chronic hepatitis B virus infection. Hepatology 67:1127-1131

Khanna, Swati; Graef, Suzanne; Mussai, Francis et al. (2018) Tumor-Derived GM-CSF Promotes Granulocyte Immunosuppression in Mesothelioma Patients. Clin Cancer Res 24:2859-2872

Ziegler, Paul K; Bollrath, Julia; Pallangyo, Charles K et al. (2018) Mitophagy in Intestinal Epithelial Cells Triggers Adaptive Immunity during Tumorigenesis. Cell 174:88-101.e16

Greten, Tim F; Korangy, Firouzeh (2018) CDK20 inhibition and immune checkpoint blockade: bringing cancer biology and tumour immunology together to develop novel treatment options for HCC. Gut 67:783-784

Ma, Chi; Zhang, Qianfei; Greten, Tim F (2018) Nonalcoholic fatty liver disease promotes hepatocellular carcinoma through direct and indirect effects on hepatocytes. FEBS J 285:752-762

Greten, Tim F (2018) The ABC of adaptive immunity in liver cancer. Hepatology 68:777-779

Ma, Chi; Han, Miaojun; Heinrich, Bernd et al. (2018) Gut microbiome-mediated bile acid metabolism regulates liver cancer via NKT cells. Science 360:

Block, Timothy M; Alter, Harvey; Brown, Nathaniel et al. (2018) Research priorities for the discovery of a cure for chronic hepatitis B: Report of a workshop. Antiviral Res 150:93-100

Brown, Zachary J; Heinrich, Bernd; Greten, Tim F (2018) Mouse models of hepatocellular carcinoma: an overview and highlights for immunotherapy research. Nat Rev Gastroenterol Hepatol :