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Metastatic CholangiocarcinomaPhase 2NCT03250273

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

A Phase 2 study testing Entinostat and Nivolumab in people with Metastatic Cholangiocarcinoma and Cholangiocarcinoma, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Entinostat and Nivolumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
44 participants
Where
1 siteUnited States
Study dates
6 Nov 2017to 20 Nov 2020
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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
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  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Sidney Kimmel Comprehensive Cancer Center

    Baltimore, Maryland, 21231

Other trials in United States

About this study

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

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).

Being tested
Entinostat, Nivolumab
Keywords
Immunotherapy, Nivolumab, Entinostat, Pancreatic Adenocarcinoma, Cholangiocarcinoma, Unresectable, Metastatic, PD-1, Antibody
Medical subject headings
Cholangiocarcinoma, Pancreatic Neoplasms, Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EntinostatDrug

    Also called SNDX-275

    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).

  • NivolumabDrug

    Also called OPDIVO, BMS-936558, MDX1106, ONO-4538

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

  • EntinostatDrug

    Also called SNDX-275

    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).

  • NivolumabDrug

    Also called OPDIVO, BMS-936558, MDX1106, ONO-4538

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

Study groups in NCT03250273
Study groupRoleWhat they receive
Arm A - CholangiocarcinomaExperimentalNot described
Receives: Drug: Entinostat; Drug: Nivolumab
ARM B - Pancreatic CancerExperimentalNot described
Receives: Drug: Entinostat; Drug: Nivolumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective Response Rate (ORR) Using Response Evaluation Criteria for Solid Tumors (RECIST 1.1)

    Objective Response Rate (ORR) is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on RECIST 1.1 criteria. CR = disappearance of all target lesions, PR is =>30% decrease in sum of diameters of target lesions. Subjects who discontinue due to clinical progression prior to post-baseline tumor assessments were considered as non-responders.

    Measured: 27 months

Secondary outcomes (10)

  1. Number of Patients Experiencing a Grade 3 or Above Treatment-related Adverse Event (AE)

    When calculating the incidence of AEs, each AE (as defined by NCI CTCAE v4.03) will be counted only once for a given subject.

    Measured: 29 months

  2. Overall Survival (OS)

    OS is defined as the duration of time from start of study treatment to time of death (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis). Estimation based on the Kaplan-Meier curve.

    Measured: 38 months

  3. Overall Survival (OS) at 6 Months

    OS is defined as the proportion of subjects who are alive at 6 months. Estimation based on the Kaplan-Meier curve.

    Measured: 6 months

  4. Overall Survival (OS) at 12 Months

    OS is defined as the proportion of subjects who are alive at 12 months. Estimation based on the Kaplan-Meier curve.

    Measured: 12 months

  5. Overall Survival (OS) at 24 Months

    OS is defined as the proportion of subjects who are alive at 24 months. Estimation based on the Kaplan-Meier curve.

    Measured: 24 months

  6. Overall Survival (OS) at 36 Months

    OS is defined as the proportion of subjects who are alive at 36 months. Estimation based on the Kaplan-Meier curve.

    Measured: 36 months

  7. Duration of Response (DOR)

    Duration of response (DOR) will be calculated for subjects who achieve a best overall response of CR or PR. DOR is defined as the number of months from the start date of PR or CR (whichever response is recorded first) and subsequently confirmed to the first date that recurrent or progressive disease or death is documented. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is >20% increase in sum of diameters of target lesions.

    Measured: 27 months

  8. Progression Free Survival (PFS) at 6 Months

    PFS is defined as the proportion of patients without disease progression (PD or relapse from CR) or death due to any cause at 6 months. Disease progression will be assessed using RECIST (version 1.1). Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is >20% increase in sum of diameters of target lesions, Stable Disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions.Estimation based on the Kaplan-Meier curve.

    Measured: 6 months

  9. Progression Free Survival (PFS) at 12 Months

    PFS is defined as the proportion of patients without disease progression (PD or relapse from CR) or death due to any cause at 12 months. Disease progression will be assessed using RECIST (version 1.1). Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is >20% increase in sum of diameters of target lesions, Stable Disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions.Estimation based on the Kaplan-Meier curve.

    Measured: 12 months

  10. Progression Free Survival (PFS) at 24 Months

    PFS is defined as the proportion of patients without disease progression (PD or relapse from CR) or death due to any cause at 24 months. Disease progression will be assessed using RECIST (version 1.1). Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is >20% increase in sum of diameters of target lesions, Stable Disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions.Estimation based on the Kaplan-Meier curve.

    Measured: 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Aug 2017
  2. Study start6 Nov 2017
  3. Primary completion20 Nov 2020
  4. Study completion20 Nov 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
44 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03250273
Sponsor's protocol ID
J1798
Other IDs
IRB00142149, 5P01CA247886
Status last verified
May 2025
First submitted
28 Jul 2017
Last updated
28 May 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Baretti M, Danilova L, Durham JN, Betts CB, Cope L, Sidiropoulos DN, Tandurella JA, Charmsaz S, Gross N, Hernandez A, Ho WJ, Thoburn C, Walker R, Leatherman J, Mitchell S, Christmas B, Saeed A, Gaykalova DA, Yegnasubramanian S, Fertig EJ, Coussens LM, Yarchoan M, Jaffee E, Azad NS. Entinostat in combination with nivolumab in metastatic pancreatic ductal adenocarcinoma: a phase 2 clinical trial. Nat Commun. 2024 Nov 12;15(1):9801. doi: 10.1038/s41467-024-52528-7.

    PubMed 39532835

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Entinostat and Nivolumab in people with Metastatic Cholangiocarcinoma and Cholangiocarcinoma, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Dec 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (ORR) Using Response Evaluation Criteria for Solid Tumors (RECIST 1.1) (time frame: 27 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03250273, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 May 2025.

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