NCT05967182

A Single-Arm Study of Pembrolizumab With Gemcitabine and Cisplatin as Perioperative Therapy for Potentially Resectable Intrahepatic Cholangiocarcinoma

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 24 (estimated)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

To find out if adding pembrolizumab to standard of care chemotherapy drugs (cisplatin and gemcitabine) will improve long-term response of intrahepatic cholangiocarcinoma after surgery, compared to treatment with surgery and standard chemotherapy alone.

Detailed description

Primary Objectives and Endpoints: * To evaluate RFS. RFS will be defined as time from curative-intent surgery to disease recurrence. Median, 9-month, and 12-month RFS rates will be measured. * To evaluate the rate of major pathologic response. Pathologic response will be assessed both by determining the percentage of the bulk tumor made up of viable cancer cells, with \< 10% signifying a major pathologic response, and by evaluating indicators of immune-mediated pathologic response which incorporate elements of tumor necrosis and fibroinflammatory stroma. Primary Endpoints: RFS rate, major pathologic response rate Secondary Objectives and Endpoints: Objectives: To assess safety and other markers of efficacy, including objective response rate (ORR) and overall survival (OS). Secondary Endpoints: * To evaluate the safety and efficacy of pembrolizumab in combination with gemcitabine and cisplatin * Safety profile per CTCAE v5.0, including term, incidence, severity, and duration of AEs * Objective response rate (ORR) by RECIST 1.1 criteria * 12- and 24-month overall survival (OS) by RECIST 1.1 criteria * Median progression free survival (PFS) and median overall survival (OS) according to RECIST v1.1 Exploratory Objectives and Endpoints: * Correlative studies will be performed to assess the immunologic response to neoadjuvant pembrolizumab with gemcitabine and cisplatin including but not limited to blood and tissue-based biomarkers, gene alterations, immunologic markers and pharmacodynamic markers from study treatment. * To assess and correlate gut microbiome diversity, composition, structure, and functional characteristics pre- and post-NAT. * To assess the biliary microbiome diversity, composition and functional characteristics (if bile is able to be collected at the time of surgery), and to compare the biliary microbiome to pre- and post-NAT gut microbiome, as well as to clinicopathologic outcomes. * To evaluate the effects of pembrolizumab on pharmacodynamic markers: ctDNA, tissue biopsies, and/or blood to assess biomarkers. include, but are not limited to, circulating tumor DNA and exosome analyses, gene expression studies, reverse phase protein arrays (RPPA, and Nanostring and/or RNA-exome to assess mRNA expression.

Conditions

• Cholangiocarcinoma

Interventions

Type	Name	Description
DRUG	Pembrolizumab	Given by IV (vein)
DRUG	Gemcitabine	Given by IV (vein)
DRUG	Cisplatin	Given by IV (vein)

Timeline

• Start date: 2024-01-16
• Primary completion: 2027-07-31
• Completion: 2029-07-31
• First posted: 2023-08-01
• Last updated: 2026-04-16

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study