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

Cholangiocarcinoma Clinical Trial

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

Status Recruiting

Clinical Trial 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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Cholangiocarcinoma

• NCT number: NCT05967182
• Study type: Interventional
• Source: M.D. Anderson Cancer Center
• Contact: Hop Tran Cao, MD
• Phone: (713) 745-4670
• Email: hstran@mdanderson.org
• Status: Recruiting
• Phase: Phase 2
• Start date: January 16, 2024
• Completion date: July 31, 2029