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

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ClinicalTrials.gov Identifier: NCT03250273
Recruitment Status : Recruiting
First Posted : August 15, 2017
Last Update Posted : October 18, 2018
Sponsor:
Collaborators:
Syndax Pharmaceuticals
Bristol-Myers Squibb
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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

Condition or disease Intervention/treatment Phase
Previously Treated Unresectable or Metastatic Cholangiocarcinoma and Pancreatic Cancer Cholangiocarcinoma Pancreatic Cancer Metastatic Pancreatic Cancer Drug: Entinostat Drug: Nivolumab Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 54 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : November 6, 2017
Estimated Primary Completion Date : November 2020
Estimated Study Completion Date : November 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Nivolumab

Arm Intervention/treatment
Experimental: Arm A - Cholangiocarcinoma Drug: Entinostat
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).
Other Name: MS-27-275, MS-275, SNDX-275

Drug: Nivolumab
After both lead-in doses of entinostat, nivolumab (240 mg) will be administered every 2 weeks (day 1 and day 15 of a cycle).
Other Name: OPDIVO

Experimental: ARM B - Pancreatic Cancer Drug: Entinostat
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).
Other Name: MS-27-275, MS-275, SNDX-275

Drug: Nivolumab
After both lead-in doses of entinostat, nivolumab (240 mg) will be administered every 2 weeks (day 1 and day 15 of a cycle).
Other Name: OPDIVO




Primary Outcome Measures :
  1. a. Objective response rate (ORR) using Response Evaluation Criteria for Solid Tumors (RECIST 1.1) [ Time Frame: 4 years ]

Secondary Outcome Measures :
  1. Number of participants experiencing study drug-related toxicities [ Time Frame: 4 years ]
  2. Progression free survival (PFS) status at 6, 12 and 24 months. [ Time Frame: 2 years ]
  3. Overall survival (OS) [ Time Frame: 4 years ]
  4. OS at 6 months, at 1, 2 and 3 years [ Time Frame: 3 years ]
  5. Duration of response (DOR) [ Time Frame: 4 years ]


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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03250273


Contacts
Contact: Susan Sartorius-Mergenthaler, RN 410-614-3644 Sartosu@jhmi.edu
Contact: Jane Zorzi, RN 410-614-5818 Jzorzi1@jhmi.edu

Locations
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center Recruiting
Baltimore, Maryland, United States, 21231
Contact: Susan Sartorius-Mergenthaler, RN    410-614-3644    Sartosu@jhmi.edu   
Contact: Jane Zorzi, RN    410-614-5818    Jzorzi1@jhmi.edu   
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Syndax Pharmaceuticals
Bristol-Myers Squibb
Investigators
Principal Investigator: Nilofer Azad, MD Johns Hopkins University

Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT03250273     History of Changes
Other Study ID Numbers: J1798
IRB00142149 ( Other Identifier: JHMI IRB )
First Posted: August 15, 2017    Key Record Dates
Last Update Posted: October 18, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
Immunotherapy
Nivolumab
Entinostat
Pancreatic Adenocarcinoma
Cholangiocarcinoma
Unresectable
Metastatic
PD-1
Antibody

Additional relevant MeSH terms:
Adenocarcinoma
Pancreatic Neoplasms
Cholangiocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Nivolumab
Entinostat
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action