- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03250273
A Clinical Trial of Entinostat in Combination With Nivolumab for Patients With Previously Treated Unresectable or Metastatic Cholangiocarcinoma and Pancreatic Adenocarcinoma
January 4, 2024 updated by: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
A Phase 2 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).
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
44
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Maryland
-
Baltimore, Maryland, United States, 21231
- Sidney Kimmel Comprehensive Cancer Center
-
-
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.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Age ≥18 years.
- Have histologically or cytologically proven cholangiocarcinoma or adenocarcinoma of the pancreas that is metastatic or unresectable.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Life expectancy of greater than 12 weeks.
- Patients must have adequate organ and marrow function defined by study-specified laboratory tests.
- Woman of child bearing potential must have a negative pregnancy test.
- Must have progressive measurable disease.
- Must have an accessible non-bone tumor that can be biopsied.
- Must use acceptable form of birth control while on study.
- Willing to provide tissue and blood samples.
- Ability to understand and willingness to sign a written informed consent document.
Exclusion Criteria:
- Chemotherapy, radiotherapy, investigational therapy, or surgery less than 3 weeks prior to trial registration
- Prior treatment with epigenetic therapy (such as entinostat, panobinostat, vorinostat, romidepsin, 5-azacitidine, or decitabine)
- Prior treatment with immunotherapy agents (including, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA4, etc.).
- Hypersensitivity reaction to any monoclonal antibody.
- History of any autoimmune disease: inflammatory bowel disease, (including ulcerative colitis and Crohn's Disease), rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemic lupus erythematosus (SLE) autoimmune vasculitis (e.g., Wegener's Granulomatosis), central nervous system (CNS) or motor neuropathy considered to be of autoimmune origin (e.g., Guillain-Barre Syndrome, Myasthenia Gravis, Multiple Sclerosis). Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (precipitating event).
- Have significant and/or malignant pleural effusion
- Has a pulse oximetry < 92% on room air.
- Known history or evidence of brain metastases.
- Conditions, including alcohol or drug dependence, intercurrent illness, or lack of sufficient peripheral venous access, that would affect the patient's ability to comply with study visits and procedures.
- Are pregnant or breastfeeding.
- Infection with HIV or hepatitis B or C.
- Patients on immunosuppressive agents.
- Requiring concurrent administration of valproic acid.
- Patients with diverticulitis, intra-abdominal abscess, or GI obstruction
- Any contraindication to oral agents.
- Another active malignancy ≤ 3 years prior to registration with the exception of non-melanotic skin cancer or carcinoma-in-situ of any type.
- Unwilling or unable to follow the study schedule for any reason.
- Evidence of ascites on imaging.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Arm A - Cholangiocarcinoma
|
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 treatment cycle).
Other Names:
After both lead-in doses of entinostat, nivolumab (240 mg) will be administered every 2 weeks (day 1 and day 15 of a cycle).
Other Names:
|
Experimental: ARM B - Pancreatic Cancer
|
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 treatment cycle).
Other Names:
After both lead-in doses of entinostat, nivolumab (240 mg) will be administered every 2 weeks (day 1 and day 15 of a cycle).
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective Response Rate (ORR) Using Response Evaluation Criteria for Solid Tumors (RECIST 1.1)
Time Frame: 27 months
|
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
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Patients Experiencing a Grade 3 or Above Treatment-related Adverse Event (AE)
Time Frame: 29 months
|
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)
Time Frame: 38 months
|
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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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)
Time Frame: 27 months
|
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
Time Frame: 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
Time Frame: 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
Time Frame: 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
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Nilofer Azad, MD, Johns Hopkins University
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 Major Dates
Study Start (Actual)
November 6, 2017
Primary Completion (Actual)
November 20, 2020
Study Completion (Actual)
November 20, 2020
Study Registration Dates
First Submitted
July 28, 2017
First Submitted That Met QC Criteria
August 14, 2017
First Posted (Actual)
August 15, 2017
Study Record Updates
Last Update Posted (Actual)
January 9, 2024
Last Update Submitted That Met QC Criteria
January 4, 2024
Last Verified
January 1, 2024
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Endocrine System Diseases
- Digestive System Neoplasms
- Endocrine Gland Neoplasms
- Pancreatic Diseases
- Adenocarcinoma
- Pancreatic Neoplasms
- Cholangiocarcinoma
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Histone Deacetylase Inhibitors
- Nivolumab
- Entinostat
Other Study ID Numbers
- J1798
- 5P01CA247886 (U.S. NIH Grant/Contract)
- IRB00142149 (Other Identifier: JHMI IRB)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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