Clinical Trials /

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

NCT03250273

Description:

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

Related Conditions:
  • Cholangiocarcinoma
  • Pancreatic Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: J1798
  • SECONDARY ID: IRB00142149
  • NCT ID: NCT03250273

Conditions

  • Previously Treated Unresectable or Metastatic Cholangiocarcinoma and Pancreatic Cancer
  • Cholangiocarcinoma
  • Pancreatic Cancer
  • Metastatic Pancreatic Cancer

Interventions

DrugSynonymsArms
EntinostatMS-27-275, MS-275, SNDX-275Arm A - Cholangiocarcinoma
NivolumabOPDIVOArm A - Cholangiocarcinoma
EntinostatMS-27-275, MS-275, SNDX-275ARM B - Pancreatic Cancer
NivolumabOPDIVOARM B - Pancreatic Cancer

Purpose

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

Trial Arms

NameTypeDescriptionInterventions
Arm A - CholangiocarcinomaExperimental
  • Entinostat
  • Nivolumab
ARM B - Pancreatic CancerExperimental
  • Entinostat
  • Nivolumab

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. 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), 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.
      
Maximum Eligible Age:100 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:a. Objective response rate (ORR) using Response Evaluation Criteria for Solid Tumors (RECIST 1.1)
Time Frame:4 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Number of participants experiencing study drug-related toxicities
Time Frame:4 years
Safety Issue:
Description:
Measure:Progression free survival (PFS) status at 6, 12 and 24 months.
Time Frame:2 years
Safety Issue:
Description:
Measure:Overall survival (OS)
Time Frame:4 years
Safety Issue:
Description:
Measure:OS at 6 months, at 1, 2 and 3 years
Time Frame:3 years
Safety Issue:
Description:
Measure:Duration of response (DOR)
Time Frame:4 years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Trial Keywords

  • Immunotherapy
  • Nivolumab
  • Entinostat
  • Pancreatic Adenocarcinoma
  • Cholangiocarcinoma
  • Unresectable
  • Metastatic
  • PD-1
  • Antibody

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