Guadecitabine and Durvalumab in Treating Patients With Advanced Liver, Pancreatic, Bile Duct, or Gallbladder Cancer
Last updated on July 2021Recruitment
- Recruitment Status
- Recruiting
- Estimated Enrollment
- Same as current
Summary
- Conditions
- Stage IIIA Gallbladder Cancer AJCC v7
- Recurrent Hepatocellular Carcinoma
- Extrahepatic Bile Duct Adenocarcinoma, Biliary Type
- Stage IV Hepatocellular Carcinoma AJCC v7
- Stage IVA Gallbladder Cancer AJCC v7
- Stage IVB Intrahepatic Cholangiocarcinoma AJCC v7
- Gallbladder Adenocarcinoma, Biliary Type
- Metastatic Pancreatic Adenocarcinoma
- Stage IIIA Hepatocellular Carcinoma AJCC v7
- Stage IVB Gallbladder Cancer AJCC v7
- Stage IV Pancreatic Cancer AJCC v6 and v7
- Recurrent Cholangiocarcinoma
- Recurrent Gallbladder Carcinoma
- Stage IIIB Hepatocellular Carcinoma AJCC v7
- Stage IVB Hepatocellular Carcinoma AJCC v7
- Recurrent Intrahepatic Cholangiocarcinoma
- Recurrent Pancreatic Carcinoma
- Stage IIIB Gallbladder Cancer AJCC v7
- Stage IVA Intrahepatic Cholangiocarcinoma AJCC v7
- Unresectable Gallbladder Carcinoma
- Stage III Gallbladder Cancer AJCC V7
- Stage III Hepatocellular Carcinoma AJCC v7
- Stage III Pancreatic Cancer AJCC v6 and v7
- Stage IIIC Hepatocellular Carcinoma AJCC v7
- Stage III Intrahepatic Cholangiocarcinoma AJCC v7
- Stage IV Gallbladder Cancer AJCC v7
- Unresectable Pancreatic Carcinoma
- Stage IVA Hepatocellular Carcinoma AJCC v7
- Type
- Interventional
- Phase
- Phase 1
- Design
- Allocation: N/AIntervention Model: Single Group AssignmentMasking: None (Open Label)Primary Purpose: Treatment
Participation Requirements
- Age
- Between 18 years and 125 years
- Gender
- Both males and females
Description
PRIMARY OBJECTIVES: I. To evaluate the dose limiting toxicities and determine the maximum tolerated dose/recommended phase 2 dose of the combination of guadecitabine and durvalumab. (Dose escalation part) II. To evaluate the objective response rate (per Response Evaluation Criteria in Solid Tumors [...
PRIMARY OBJECTIVES: I. To evaluate the dose limiting toxicities and determine the maximum tolerated dose/recommended phase 2 dose of the combination of guadecitabine and durvalumab. (Dose escalation part) II. To evaluate the objective response rate (per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) for the combination of guadecitabine and durvalumab in hepatocellular carcinoma, pancreatic cancer and cholangiocarcinoma cohorts, respectively. (Expansion part) SECONDARY OBJECTIVES: I. To describe the safety and tolerability of the combination of guadecitabine and durvalumab. II. To estimate the progression-free and overall survival of patients with advanced hepatocellular carcinoma (HCC), pancreatic cancer and biliary cancers treated with the combination of guadecitabine and durvalumab. TERTIARY OBJECTIVES: I. Correlate programmed cell death ligand 1 (PD-L1) and programmed cell death protein 1 (PD1) expression on various cells within tumor samples and anti-tumor effect (response rate and survival). II. Correlate effector T cells (Teff)/regulatory T cells (Treg) ratio in the tumor and anti-tumor effect. III. Correlate granulocytic and monocytic myeloid-derived suppressor cells (MDSCs) level in the peripheral blood using fluorescence-activated cell sorting (FACS) and anti-tumor effect. IV. Evaluate changes in inflammatory T cell signatures pre and post treatment and potential associations with anti-tumor effect. V. Assess the induction, activation, expansion and tumor infiltration of tumor neo-epitope-specific T cells. VI. Explore changes in gene methylation and expression with anti-tumor effect, with particular emphasis on the ancestry-informative marker (AIM) gene panel. VII. Correlate immunologic changes in pre- and post-treatment peripheral blood mononuclear cell (PBMCs) and anti-tumor effect. OUTLINE: This is a dose-escalation study of guadecitabine. Patients receive guadecitabine subcutaneously (SC) once daily (QD) on days 1-5 and durvalumab intravenously (IV) over 60 minutes on day 8. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 2 months.
Tracking Information
- NCT #
- NCT03257761
- Collaborators
- National Cancer Institute (NCI)
- Van Andel Research Institute
- Investigators
- Principal Investigator: Anthony El-Khoueiry, MD University of Southern California