A Clinical Trial Of Entinostat In Combination With Nivolumab For Patients With Previously Treated Unresectable Or Metastatic Cholangiocarcinoma And Pancreatic Adenocarcinoma

Study Overview

A Clinical Trial of Entinostat in Combination With Nivolumab for Patients With Previously Treated Unresectable or Metastatic Cholangiocarcinoma and Pancreatic Adenocarcinoma

The proposed study is an open-label, two-arm study of entinostat plus nivolumab in patients with unresectable or metastatic cholangiocarcinoma (CCA) or pancreatic ductal adenocarcinoma (PDAC).

N/A

Metastatic Cholangiocarcinoma
Cholangiocarcinoma
Pancreatic Cancer
Metastatic Pancreatic Cancer
Unresectable Pancreatic Cancer
Unresectable Cholangiocarcinoma

DRUG: Entinostat
DRUG: Nivolumab
DRUG: Entinostat
DRUG: Nivolumab

J1798
IRB00142149 (OTHER Identifier) (OTHER: JHMI IRB)
5P01CA247886 (U.S. NIH Grant/Contract)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2017-07-28	Results First Submitted 2021-11-17	Last Update Submitted that met QC Criteria 2024-01-04
First Submitted that Met QC Criteria 2017-08-14	Results First Submitted that Met QC Criteria 2021-11-17	Last Update Posted (ACTUAL) 2024-01-09
First Posted (ACTUAL) 2017-08-15	Results First Posted 2021-12-16	Last Verified 2024-01

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Arm A - Cholangiocarcinoma	DRUG: Entinostat Entinostat (5mg) will be administered starting with 2 lead-in doses at 14 and 7 days before the first dose of nivolumab in combination with entinostat. After the lead-in dose, entinostat will be administered once a week (days 1, 8, 15, and 21 of each trea DRUG: Nivolumab After both lead-in doses of entinostat, nivolumab (240 mg) will be administered every 2 weeks (day 1 and day 15 of a cycle).
EXPERIMENTAL: ARM B - Pancreatic Cancer	DRUG: Entinostat Entinostat (5mg) will be administered starting with 2 lead-in doses at 14 and 7 days before the first dose of nivolumab in combination with entinostat. After the lead-in dose, entinostat will be administered once a week (days 1, 8, 15, and 21 of each trea DRUG: Nivolumab After both lead-in doses of entinostat, nivolumab (240 mg) will be administered every 2 weeks (day 1 and day 15 of a cycle).

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Arm A - Cholangiocarcinoma

DRUG: Entinostat

Entinostat (5mg) will be administered starting with 2 lead-in doses at 14 and 7 days before the first dose of nivolumab in combination with entinostat. After the lead-in dose, entinostat will be administered once a week (days 1, 8, 15, and 21 of each trea

DRUG: Nivolumab

After both lead-in doses of entinostat, nivolumab (240 mg) will be administered every 2 weeks (day 1 and day 15 of a cycle).

EXPERIMENTAL: ARM B - Pancreatic Cancer

DRUG: Entinostat

Entinostat (5mg) will be administered starting with 2 lead-in doses at 14 and 7 days before the first dose of nivolumab in combination with entinostat. After the lead-in dose, entinostat will be administered once a week (days 1, 8, 15, and 21 of each trea

DRUG: Nivolumab

After both lead-in doses of entinostat, nivolumab (240 mg) will be administered every 2 weeks (day 1 and day 15 of a cycle).

Primary Outcome Measures	Measure Description	Time Frame
Objective Response Rate (ORR) Using Response Evaluation Criteria for Solid Tumors (RECIST 1.1)	Objective Response Rate (ORR) is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on RECIST 1.1 criteria. CR = disappearance of all target lesions, PR is =>30% decrease in sum of diameters of target lesions. Subjects who discontinue due to clinical progression prior to post-baseline tumor assessments were considered as non-responders.	27 months

Secondary Outcome Measures	Measure Description	Time Frame
Number of Patients Experiencing a Grade 3 or Above Treatment-related Adverse Event (AE)	When calculating the incidence of AEs, each AE (as defined by NCI CTCAE v4.03) will be counted only once for a given subject.	29 months
Overall Survival (OS)	OS is defined as the duration of time from start of study treatment to time of death (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis). Estimation based on the Kaplan-Meier curve.	38 months
Overall Survival (OS) at 6 Months	OS is defined as the proportion of subjects who are alive at 6 months. Estimation based on the Kaplan-Meier curve.	6 months
Overall Survival (OS) at 12 Months	OS is defined as the proportion of subjects who are alive at 12 months. Estimation based on the Kaplan-Meier curve.	12 months
Overall Survival (OS) at 24 Months	OS is defined as the proportion of subjects who are alive at 24 months. Estimation based on the Kaplan-Meier curve.	24 months
Overall Survival (OS) at 36 Months	OS is defined as the proportion of subjects who are alive at 36 months. Estimation based on the Kaplan-Meier curve.	36 months
Duration of Response (DOR)	Duration of response (DOR) will be calculated for subjects who achieve a best overall response of CR or PR. DOR is defined as the number of months from the start date of PR or CR (whichever response is recorded first) and subsequently confirmed to the first date that recurrent or progressive disease or death is documented. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is >20% increase in sum of diameters of target lesions.	27 months
Progression Free Survival (PFS) at 6 Months	PFS is defined as the proportion of patients without disease progression (PD or relapse from CR) or death due to any cause at 6 months. Disease progression will be assessed using RECIST (version 1.1). Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is >20% increase in sum of diameters of target lesions, Stable Disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions.Estimation based on the Kaplan-Meier curve.	6 months
Progression Free Survival (PFS) at 12 Months	PFS is defined as the proportion of patients without disease progression (PD or relapse from CR) or death due to any cause at 12 months. Disease progression will be assessed using RECIST (version 1.1). Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is >20% increase in sum of diameters of target lesions, Stable Disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions.Estimation based on the Kaplan-Meier curve.	12 months
Progression Free Survival (PFS) at 24 Months	PFS is defined as the proportion of patients without disease progression (PD or relapse from CR) or death due to any cause at 24 months. Disease progression will be assessed using RECIST (version 1.1). Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is >20% increase in sum of diameters of target lesions, Stable Disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions.Estimation based on the Kaplan-Meier curve.	24 months

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Syndax Pharmaceuticals
Bristol-Myers Squibb
National Cancer Institute (NCI)

Investigators

PRINCIPAL_INVESTIGATOR: Nilofer Azad, MD, Johns Hopkins University

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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