Perioperative Gemcitabine, Cisplatin, and Pembrolizumab in Potentially Resectable Biliary Tract Cancers

NCT06001658 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: J2390IRB00371087
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the safety of peri-operative gemcitabine, cisplatin, and pembrolizumab in patients with BTC, as well as whether the combination of gemcitabine, cisplatin, and pembrolizumab (gem/cis/pembro) is feasible and lead to pathologic responses.

Conditions

Billiary Track Cancer

Keywords

Biliary Tract cancer; Pembrolizumab; Gemcitabine; Cisplatin; Immunotherapy; Potentially resectable biliary tract cancer; Anti PD-L1; PD-L1; Carcinoma

Outcome Measures

Primary Outcomes (1)

• Average minimum Euclidean distance from CD8+ T cells to immunosuppressive tumor-associated macrophages (TAMs) at the per-cell level in patients with a major pathologic response versus pathologic non-responders.

  The evaluable population of this endpoint consist of all patients who receive at least one dose of study drug and have TAMs and CD8 T cell measures at the time of surgery. TAMs being evaluated are the following: immunosuppressive TAMs with high Arginase-1 expression (CD68+CD163+Arg-1hiPDL1-/+), immunosuppressive TAMs with low Arginase-1 expression (CD68+CD163+Arg-1lo PDL1-/+), and less immunosuppressive TAMs (CD68+CD163-HLA-DRhi/CD86hi/PDL1hi)

  4 years

Secondary Outcomes (4)

• Number of participants experiencing grade 3 or above drug-related toxicities

  4 years

• Number of patients proceeding to surgery without an extended treatment-related delay as a measure of feasibility

  144 days

• Major pathologic response rate

  8-12 weeks

• R0 resection rate

  60 days

Study Arms (1)

Gemcitabine, Cisplatin and Pembrolizumab

EXPERIMENTAL

Drug: Gemcitabine; Drug: Cisplatin; Drug: Pembrolizumab

Interventions

Gemcitabine DRUG

Patients will receive treatment on Day 1 and Day 8 of each cycle. Gemcitabine (1000 mg/m2) will be administered IV on Day 1 and Day 8 of each cycle, Q3 weeks with 2 - 4 cycles prior to surgery and then 4-6 cycles after surgery.

Gemcitabine, Cisplatin and Pembrolizumab

Cisplatin DRUG

Patients will receive treatment on Day 1 and Day 8 of each cycle. Cisplatin (25 mg/m2) will be administered IV on Day 1 and Day 8 of each cycle, Q3 weeks with 2 - 4 cycles prior to surgery and then 4-6 cycles after surgery.

Gemcitabine, Cisplatin and Pembrolizumab

Pembrolizumab DRUG

Patients will receive treatment on Day 1 of each cycle. Pembrolizumab (200 mg) will be administered IV on Day 1 of each cycle, Q3 weeks with 2 - 4 cycles prior to surgery and then 4-6 cycles after surgery. Pembrolizumab (400 mg) will be administered IV Q6 weeks up to 4 cycles as maintenance.

Also known as: KEYTRUDA; anti-PD-1 mAb

Gemcitabine, Cisplatin and Pembrolizumab

Eligibility Criteria

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

You may qualify if:

• Must have a newly diagnosed, biopsy-proven biliary tract cancer (BTC) including gallbladder, intrahepatic, extrahepatic, and hilar cholangiocarcinoma.
• Resectable BTC (biliary tract cancer)
• Measurable disease per RECIST 1.1 as determined by the investigator.
• Age ≥18 years.
• ECOG (Eastern Cooperative Oncology Group) performance status ≤1 or Karnofsky ≥80
• Patients must have adequate organ and marrow function defined by study-specified laboratory tests.
• Patients must have adequate liver function defined by study-specified laboratory tests.
• Patients with chronic or acute HBV or HCV infection must have disease controlled prior to enrollment.
• Women of childbearing potential (WOCBP) must have a negative urine or serum pregnancy test.
• For both Women and Men, must use acceptable form of birth control while on study.
• Ability to understand and willingness to sign a written informed consent document.

You may not qualify if:

• Receiving, or previously received, any systemic chemotherapy, or investigational agent for BTC.
• Has received prior radiotherapy within 2 weeks of start of study intervention.
• Patients with a history of prior treatment with anti-PD-1 and anti-PD-L1.
• Have been diagnosed with another cancer or myeloproliferative disorder whose natural history or treatment has the potential to interfere with safety or efficacy assessment of this study's investigational drugs.
• Has a known history of Human Immunodeficiency Virus (HIV)/AIDS
• Has active co-infection with HBV and HDV.
• Has a diagnosis of immunodeficiency.
• Has active autoimmune disease that has required systemic treatment in the past 2 years.
• Systemic or topical corticosteroids at immunosuppressive doses.
• Prior allogeneic stem cell transplantation or organ transplantation.
• Prior tissue or organ allograft or allogeneic bone marrow transplantation, including corneal transplants.
• Uncontrolled intercurrent active medical and/or psychiatric illness/social psychosocial problems that that would limit compliance with study requirements.
• Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, metastatic cancer, or psychiatric illness/social situations that would limit compliance with study requirements.
• Evidence of clinical ascites.
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

SKCCC Johns Hopkins

Baltimore, Maryland, 21231, United States

RECRUITING

MeSH Terms

Conditions

Biliary Tract Neoplasms; Carcinoma

Interventions

Gemcitabine; Cisplatin; pembrolizumab

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Marina Baretti, M.D.

  SKCCC Johns Hopkins Medical Institution

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Colleen Apostal, RN

CONTACT

410-614-3644; GIClinicalTrials@jhmi.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2023
• First Posted: August 21, 2023
• Study Start: July 8, 2024
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: December 3, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)