Clinical trial NCT03250273: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Cholangiocarcinoma
Cholangiocarcinoma
Pancreatic Cancer
Metastatic Pancreatic Cancer
Unresectable Pancreatic Cancer
Unresectable Cholangiocarcinoma
Keywords: Immunotherapy
Nivolumab
Entinostat
Pancreatic Adenocarcinoma
Cholangiocarcinoma
Unresectable
Metastatic
PD-1
Antibody
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: Syndax Pharmaceuticals
name: Bristol-Myers Squibb
name: National Cancer Institute (NCI)
First posted: 2017-08-15
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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.

Primary outcomes:
measure: Objective Response Rate (ORR) Using Response Evaluation Criteria for Solid Tumors (RECIST 1.1)
timeFrame: 27 months
Secondary outcomes:
measure: Number of Patients Experiencing a Grade 3 or Above Treatment-related Adverse Event (AE)
timeFrame: 29 months
measure: Overall Survival (OS)
timeFrame: 38 months
measure: Overall Survival (OS) at 6 Months
timeFrame: 6 months
measure: Overall Survival (OS) at 12 Months
timeFrame: 12 months
measure: Overall Survival (OS) at 24 Months
timeFrame: 24 months
measure: Overall Survival (OS) at 36 Months
timeFrame: 36 months
measure: Duration of Response (DOR)
timeFrame: 27 months
measure: Progression Free Survival (PFS) at 6 Months
timeFrame: 6 months
measure: Progression Free Survival (PFS) at 12 Months
timeFrame: 12 months
measure: Progression Free Survival (PFS) at 24 Months
timeFrame: 24 months
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Nilofer Azad, MD
role: PRINCIPAL_INVESTIGATOR
References: