A Phase Ib Study of Guadecitabine (SGI-110) and Durvalumab (MEDI 4736) in Patients with Advanced Hepatocellular Carcinoma, Pancreatic Adenocarcinoma, and Cholangiocarcinoma/Gallbladder Cancer
Johns Hopkins Kimmel Cancer Center in Baltimore
•To find the highest safe doses of guadecitabine and durvalumab when given together •To test the safety of guadecitabine and durvalumab when given together•To determine the side effects of guadecitabine and durvalumab when given together•To see whether guadecitabine and durvalumab when given together can shrink tumors in people with advanced pancreatic, gallbladder, liver or biliary cancer (cholangiocarcinoma) •To measure biomarkers (specific proteins that are indicators of cancer activity in the body) in tumors and blood to see if guadecitabine and durvalumab affect these biomarkers•To find the doses of guadecitabine and durvalumab that should be used in the second part of the study
Adequate normal organ and marrow function, must have measurable disease.Hepatocellular Carcinoma Specific Inclusion Criteria: Patients must have a histologically proven diagnosis of hepatocellular carcinoma that is not amenable to curative surgical therapeutic options.Patients must have had evidence of radiologic progression on sorafenib or have had intolerance to sorafenib.Hepatocellular Carcinoma Specific Exclusion Criteria:A history of hepatic encephalopathy within the past 12 months• A history of bleeding esophageal or gastric varices within the last 6 months prior to initiation of study therapy.Cholangiocarcinoma Specific Inclusion Criteria:Patients must have histologically or cytologically documented carcinoma primary to the intra- or extra-hepatic biliary system or gall bladder with clinical and/or radiologic evidence of unresectable, locally advanced or metastatic disease. Patients with ampullary carcinoma are not eligible.• Patients must have failed at least one (but no more than 2) prior line of systemic therapy in the advanced disease setting. If patient received adjuvant treatment and had disease recurrence after 6 months, patients will only be eligible after failing one regimen of systemic chemotherapy used to treat the (unresectable or metastatic) disease recurrence.• Patients who received adjuvant chemotherapy and had evidence of disease recurrence within 6 months of completion of the adjuvant treatment are also eligible.Pancreatic Cancer Specific Inclusion Criteria:Patients must have unresectable or metastatic pancreatic cancer? Patients must have failed at least one prior line of therapy for metastatic or unresectable disease or have recurred within 6 months of completing adjuvant chemotherapy.Pancreatic Cancer Specific Exclusion Criteria:Any previous treatment with a hypomethylating agent, or with a PD1 or PD-L1 or anti-PD-L2 or anti-CTLA-4inhibitor, including durvalumab
Guadecitabine will be administered subcutaneously once daily on days 1 to 5 every 28 days. Durvalumab will be administered intravenously every 4 weeks (day 8 of every cycle). One cycle will consist of 28 days.
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