A Clinical Trial of Entinostat in Combination With Nivolumab for Patients With Previously Treated Unresectable or Metastatic Cholangiocarcinoma and Pancreatic Adenocarcinoma
Condition: Metastatic Cholangiocarcinoma; Cholangiocarcinoma; Pancreatic Cancer; Metastatic Pancreatic Cancer; Unresectable Pancreatic Cancer; Unresectable Cholangiocarcinoma
MeSH terms: Adenocarcinoma; Pancreatic Neoplasms; Cholangiocarcinoma
Intervention: Entinostat; Nivolumab; Entinostat; Nivolumab
Intervention description: 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).; After both lead-in doses of entinostat, nivolumab (240 mg) will be administered every 2 weeks (day 1 and day 15 of a cycle).; 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).; After both lead-in doses of entinostat, nivolumab (240 mg) will be administered every 2 weeks (day 1 and day 15 of a cycle).
Intervention MeSH terms: Nivolumab; Entinostat
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 44.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Immunotherapy; Nivolumab; Entinostat; Pancreatic Adenocarcinoma; Cholangiocarcinoma; Unresectable; Metastatic; PD-1; Antibody

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).
    

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.