Guadecitabine and Durvalumab in Treating Patients With Advanced Liver, Pancreatic, Bile Duct, or Gallbladder Cancer
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03257761|
Recruitment Status : Active, not recruiting
First Posted : August 22, 2017
Last Update Posted : August 9, 2022
|Condition or disease||Intervention/treatment||Phase|
|Extrahepatic Bile Duct Adenocarcinoma, Biliary Type Gallbladder Adenocarcinoma, Biliary Type Metastatic Pancreatic Adenocarcinoma Recurrent Cholangiocarcinoma Recurrent Gallbladder Carcinoma Recurrent Hepatocellular Carcinoma Recurrent Intrahepatic Cholangiocarcinoma Recurrent Pancreatic Carcinoma Stage III Gallbladder Cancer AJCC V7 Stage III Hepatocellular Carcinoma AJCC v7 Stage III Intrahepatic Cholangiocarcinoma AJCC v7 Stage III Pancreatic Cancer AJCC v6 and v7 Stage IIIA Gallbladder Cancer AJCC v7 Stage IIIA Hepatocellular Carcinoma AJCC v7 Stage IIIB Gallbladder Cancer AJCC v7 Stage IIIB Hepatocellular Carcinoma AJCC v7 Stage IIIC Hepatocellular Carcinoma AJCC v7 Stage IV Gallbladder Cancer AJCC v7 Stage IV Hepatocellular Carcinoma AJCC v7 Stage IV Pancreatic Cancer AJCC v6 and v7 Stage IVA Gallbladder Cancer AJCC v7 Stage IVA Hepatocellular Carcinoma AJCC v7 Stage IVA Intrahepatic Cholangiocarcinoma AJCC v7 Stage IVB Gallbladder Cancer AJCC v7 Stage IVB Hepatocellular Carcinoma AJCC v7 Stage IVB Intrahepatic Cholangiocarcinoma AJCC v7 Unresectable Gallbladder Carcinoma Unresectable Pancreatic Carcinoma||Biological: Durvalumab Drug: Guadecitabine||Phase 1|
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)
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.
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||55 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase Ib Study of Guadecitabine (SGI-110) and Durvalumab (MEDI 4736) in Patients With Advanced Hepatocellular Carcinoma, Pancreatic Adenocarcinoma, and Cholangiocarcinoma/Gallbladder Cancer|
|Actual Study Start Date :||February 7, 2018|
|Actual Primary Completion Date :||March 2, 2021|
|Estimated Study Completion Date :||March 2, 2023|
Experimental: Treatment (guadecitabine, durvalumab)
Patients receive guadecitabine SC QD on days 1-5 and durvalumab IV over 60 minutes on day 8. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
- Incidence of adverse events [ Time Frame: Up to 56 days ]Graded according to Common Terminology Criteria for Adverse Events version 4.03.
- Tumor response (dose expansion) [ Time Frame: Up to 2 years ]Will be calculated by the percentage of patients having complete or partial response among all patients who have been treated at maximum tolerated dose/recommended phase II dose in each cohort. Will be assessed according to Response Evaluation Criteria in Solid Tumors (RECIST).
- Overall survival [ Time Frame: From start of treatment until death due to any cause, assessed up to 2 years ]Kaplan-Meier curves will be used to show overall survival in each cohort. Median overall survival and 95% confidence intervals will be derived from Kaplan-Meier curves.
- Progression-free survival [ Time Frame: From start of treatment to time of progression per RECIST 1.1 or death whichever comes first, assessed up to 2 years ]Kaplan-Meier curves will be used to show progression-free survival in each cohort. Median progression-free survival and 95% confidence intervals will be derived from Kaplan-Meier curves.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03257761
|United States, California|
|USC / Norris Comprehensive Cancer Center|
|Los Angeles, California, United States, 90033|
|Hoag Memorial Hospital Presbyterian|
|Newport Beach, California, United States, 92663|
|United States, Maryland|
|Johns Hopkins University/Sidney Kimmel Cancer Center|
|Baltimore, Maryland, United States, 21287|
|Principal Investigator:||Anthony El-Khoueiry, MD||University of Southern California|