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. We recently completed enrollment of patients in two studies: 11-C-0181. In this study we tested the effect of single agent Trc105 in patients with HCC, who progressed on sorafenib. - 12-C-0187 ISIS 183750 in combination with Irinotecan in patents who progressed standard of care in colon cancer. We continued to enroll: 11-C-0102 Sorafenib and TRC105 in HCC 1st line treatment with a combination of sorafenib+the vascular targeting agent Trc105 in patients with HCC. This study will go into phase II. 13-C-0120 anti-CTLA4 & ablative therapy Here we test the combination of ablative therapies (RFA/Tace) in combination with anti-CTLA4. 13-C-0009 NPC-1C Gem in Pancreatic Ca This is a multicenter study testing the combination of NPC1, an Ab directed against a glycosylated form of Muc5A in pancreatic cancer in combination with gemcitabine + abraxane in patients who progressed on FOLFIRINOX. We opened two protocols: 15-C-0021 A Pilot Study of AMP-224 - a PD-1 Inhibitor - in Combination with Stereotactic Body Radiation Therapy (SBRT) in Patients with Metastatic Colorectal Cancer 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. In addition we perform clinical research on patients with the aim to develop new protocols.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Cancer Institute (NCI)
• Type: Investigator-Initiated Intramural Research Projects (ZIA)
• Project #: 1ZIABC011343-06
• Application #: 9153873
• Support Year: 6
• Fiscal Year: 2015

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 :