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

Brief Title

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

Official Title

A Phase 2 Clinical Trial of Entinostat in Combination With Nivolumab for Patients With Previously Treated Unresectable or Metastatic Cholangiocarcinoma and Pancreatic Adenocarcinoma

Brief Summary

      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 Phase

Phase 2

Study Type

Interventional

Primary Outcome

Objective Response Rate (ORR) Using Response Evaluation Criteria for Solid Tumors (RECIST 1.1)

Secondary Outcome

 Number of Patients Experiencing a Grade 3 or Above Treatment-related Adverse Event (AE)

Condition

Metastatic Cholangiocarcinoma

Intervention

Entinostat

Study Arms / Comparison Groups

 Arm A - Cholangiocarcinoma

Description:  

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

44

Start Date

November 6, 2017

Completion Date

November 20, 2020

Primary Completion Date

November 20, 2020

Eligibility Criteria

        Inclusion Criteria:

          1. Age ≥18 years.

          2. Have histologically or cytologically proven cholangiocarcinoma or adenocarcinoma of
             the pancreas that is metastatic or unresectable.

          3. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

          4. Life expectancy of greater than 12 weeks.

          5. Patients must have adequate organ and marrow function defined by study-specified
             laboratory tests.

          6. Woman of child bearing potential must have a negative pregnancy test.

          7. Must have progressive measurable disease.

          8. Must have an accessible non-bone tumor that can be biopsied.

          9. Must use acceptable form of birth control while on study.

         10. Willing to provide tissue and blood samples.

         11. Ability to understand and willingness to sign a written informed consent document.

        Exclusion Criteria:

          1. Chemotherapy, radiotherapy, investigational therapy, or surgery less than 3 weeks
             prior to trial registration

          2. Prior treatment with epigenetic therapy (such as entinostat, panobinostat, vorinostat,
             romidepsin, 5-azacitidine, or decitabine)

          3. Prior treatment with immunotherapy agents (including, anti-PD-1, anti-PD-L1,
             anti-PD-L2, anti-CTLA4, etc.).

          4. Hypersensitivity reaction to any monoclonal antibody.

          5. 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).

          6. Have significant and/or malignant pleural effusion

          7. Has a pulse oximetry < 92% on room air.

          8. Known history or evidence of brain metastases.

          9. 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.

         10. Are pregnant or breastfeeding.

         11. Infection with HIV or hepatitis B or C.

         12. Patients on immunosuppressive agents.

         13. Requiring concurrent administration of valproic acid.

         14. Patients with diverticulitis, intra-abdominal abscess, or GI obstruction

         15. Any contraindication to oral agents.

         16. Another active malignancy ≤ 3 years prior to registration with the exception of
             non-melanotic skin cancer or carcinoma-in-situ of any type.

         17. Unwilling or unable to follow the study schedule for any reason.

         18. Evidence of ascites on imaging.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Nilofer Azad, MD, , 

Location Countries

United States

Location Countries

United States

NCT ID

NCT03250273

Organization ID

J1798

Secondary IDs

IRB00142149

Responsible Party

Sponsor

Study Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Collaborators

 Syndax Pharmaceuticals

Study Sponsor

Nilofer Azad, MD, Principal Investigator, Johns Hopkins University

Verification Date

August 2022