Evaluating Combination Immunotherapy for Advanced Cholangiocarcinoma With Pembrolizumab and PEG-Intron

NCT02982720 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: GI16-263
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, single-arm, multicenter Phase II safety and efficacy study of combination therapy with pembrolizumab and Sylatron (Peginterferon alpha-2b) in patients with advanced cholangiocarcinoma who have progressed on or cannot tolerate frontline chemotherapy.

Conditions

Advanced Cholangiocarcinoma

Keywords

cholangiocarcinoma; Pembrolizumab; MK-3475; Sylatron; peginterferon alfa-2b

Outcome Measures

Primary Outcomes (1)

• Asses Objective Response Rate (ORR) of All Patients Receiving Pembrolizumab and Sylatron Combination Therapy

  Defined as the proportion of subjects who achieve the best response (CR and PR) determined by RECIST1.1

  12 months

Secondary Outcomes (4)

• Assess Progression Free Survival (PFS) of Patients Receiving Pembrolizumab and Sylatron

  36 months

• Asses Overall Survival (OS) of Patients Receiving Pembrolizumab and Sylatron

  36 months

• Assess Objective Response Rate (ORR)

  36 months

• Assess Adverse Events, Serious Adverse Events and Serious Adverse Events Leading to Discontinuation of the Treatment (Death) of Combined Pembrolizumab and Sylatron Therapy.

  36 months

Study Arms (1)

Pembrolizumab and Sylatron

EXPERIMENTAL

Pembrolizumab will be administered intravenously at a dose of 200 mg every 3 weeks starting week 4. Sylatron will be administered at a dose of 200mcg subcutaneously weekly starting at week 1.

Drug: Pembrolizumab; Drug: Sylatron

Interventions

Pembrolizumab DRUG

Pembrolizumab will be administered intravenously.

Also known as: MK-3475

Pembrolizumab and Sylatron

Sylatron DRUG

Sylatron will be administered subcutaneously.

Also known as: Peginterferon alfa-2b

Pembrolizumab and Sylatron

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be willing and able to provide written informed consent/assent for the trial.
• Be at least 18 years of age on day of signing informed consent.
• Patients must have received 1 line of prior systemic therapy for metastatic or resectable disease (i.e. patients may have received adjuvant gemcitabine and then later gemcitabine/cisplatin for recurrent metastatic disease)
• Histological confirmation of cholangiocarcinoma.
• Have measurable disease based on RECIST 1.1.
• Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1. Subjects for whom newly obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the sponsor-investigator.
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
• Demonstrate adequate organ function:
• Hematological:
• Absolute neutrophil count (ANC) ≥ 1,500 /μL
• Platelets ≥ 100,000 / μL
• Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment)
• Renal:
• Serum creatinine OR Measured or calculated creatinine clearance ≤ 1.5 X upper limit of normal (ULN) OR ≥ 60 mL/min for subject with creatinine levels
• (GFR can also be used in place of creatinine or CrCl) \> 1.5 x institutional ULN

You may not qualify if:

• The subject must be excluded from participating in the trial if the subject:
• A history of anaphylaxis to peginterferon alfa-2b or interferon alfa-2b
• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Has a known history of active Bacillus Tuberculosis (TB)
• Hypersensitivity to pembrolizumab or any of its excipients.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
• Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
• Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has known history of, or any evidence of active, non-infectious pneumonitis.
• Has an active infection requiring systemic therapy.

Sponsors & Collaborators

• Aiwu Ruth He, MD: lead
• Merck Sharp & Dohme LLC: collaborator
• Roswell Park Cancer Institute: collaborator
• The Cleveland Clinic: collaborator
• Georgetown University: collaborator
• Hoosier Cancer Research Network: collaborator

Study Sites (1)

Georgetown Lombardi Comprehensive Cancer Center

Washington D.C., District of Columbia, 20007, United States

Location

Related Links

• Hoosier Cancer Research Network Website

MeSH Terms

Conditions

Cholangiocarcinoma

Interventions

pembrolizumab; peginterferon alfa-2b

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Limitations and Caveats

This study was terminated by the funder due to the discontinuation of Sylatron.

Results Point of Contact

• Title: Clinicaltrials.gov Results Coordinator
• Organization: Hoosier Cancer Research Network

jsmith@hoosiercancer.org

317.921.2050

Study Officials

• Aiwu R. He, MD PhD

  Lombardi Comprehensive Cancer Center Georgetown University

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: Open-Label
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: December 1, 2016
• First Posted: December 5, 2016
• Study Start: July 5, 2017
• Primary Completion: February 9, 2018
• Study Completion: February 9, 2018
• Last Updated: February 16, 2022
• Results First Posted: June 5, 2019

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)