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

Tumor Microenvironment Features of Response to Perioperative Gemcitabine, Cisplatin, and Pembrolizumab in Potentially Resectable Biliary Tract Cancers

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.

Study Overview

• Status: Recruiting
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: Gemcitabine; Drug: Cisplatin; Drug: Pembrolizumab

• Study Type: Interventional
• Enrollment (Estimated): 27
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Joann Santmyer, RN; Phone Number: 410-614-3644; Email: GIClinicalTrials@jhmi.edu
• Study Contact Backup: Name: Colleen Apostal, RN; Phone Number: 410-614-3644; Email: GIClinicalTrials@jhmi.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Recruiting
      • SKCCC Johns Hopkins
      • Contact: Joann Santmyer, RN; Phone Number: 410-614-3644; Email: GIClinicalTrials@jhmi.edu
      • Contact: Colleen Apostol, RN; Phone Number: 410-614-3644; Email: GIClinicalTrials@jhmi.edu
      • Principal Investigator: Marina Baretti, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.
• Previously identified allergy or hypersensitivity to monoclonal antibodies or any component of the study treatment formulations.
• Pregnant or breastfeeding.
• WOCBP and men with female partners (WOCBP) who are not willing to use contraception.
• Subjects unable to undergo venipuncture and/or tolerate venous access.
• Patient is at the time of signing informed consent a regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Gemcitabine, Cisplatin and Pembrolizumab

Drug: Gemcitabine; 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.; Drug: Cisplatin; 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.; Drug: Pembrolizumab; 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.; Other Names: KEYTRUDA; anti-PD-1 mAb

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants experiencing grade 3 or above drug-related toxicities	When calculating the incidence of AEs, each AE (as defined by NCI CTCAE v5.0) will be counted only once for a given subject.	4 years
Number of patients proceeding to surgery without an extended treatment-related delay as a measure of feasibility	Extended treatment delay is defined as a delay of greater than 60 days of the pre-planned surgical evaluation date, or inability to go to surgery due to an adverse event related to study treatment.	144 days
Major pathologic response rate	The number of participants with a major pathologic response as defined by ≤ 10% residual viable tumor cells in the resection of the primary tumor and lymph nodes.	8-12 weeks
R0 resection rate	The number of participants with a R0 resection as defined by a microscopically margin-negative resection, in which no tumor (gross or microscopic) remains in the primary tumor bed.	60 days

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Marina Baretti, M.D., SKCCC Johns Hopkins Medical Institution

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2028

Study Registration Dates

• First Submitted: August 8, 2023
• First Submitted That Met QC Criteria: August 16, 2023
• First Posted (Actual): August 21, 2023

Study Record Updates

• Last Update Posted (Actual): May 3, 2024
• Last Update Submitted That Met QC Criteria: May 2, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Gemcitabine; Carcinoma; Immunotherapy; Cisplatin; Pembrolizumab; PD-L1; Anti PD-L1; Biliary Tract cancer; Potentially resectable biliary tract cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Biliary Tract Diseases; Biliary Tract Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab; Gemcitabine
• Other Study ID Numbers: J2390; IRB00371087 (Other Identifier: Johns Hopkins Medicine Internal Review Board)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No