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

Johns Hopkins Medicine

Status and phase

Completed

Phase 2

Conditions

Metastatic Pancreatic Cancer

Metastatic Cholangiocarcinoma

Cholangiocarcinoma

Unresectable Cholangiocarcinoma

Unresectable Pancreatic Cancer

Pancreatic Cancer

Treatments

Drug: Entinostat

Drug: Nivolumab

Study type

Interventional

Funder types

Other

Industry

NIH

Identifiers

NCT03250273

J1798

IRB00142149 (Other Identifier)

5P01CA247886 (Other Identifier)

Details and patient eligibility

About

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).

Enrollment

44 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.