NCT06050252

Testing the Combination of the Anticancer Drug Durvalumab With Chemotherapy (Gemcitabine and Cisplatin) at Improving Outcomes for High-Risk Resectable Liver Cancer Before Surgery

A Phase II Trial of Durvalumab With Gemcitabine and Cisplatin as Neoadjuvant Therapy for High-Risk Resectable Intrahepatic Cholangiocarcinoma

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 27 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial tests how well giving durvalumab with standard chemotherapy, gemcitabine and cisplatin, before surgery works in treating patients with high risk liver cancer (cholangiocarcinoma) that can be removed by surgery (resectable). Durvalumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as gemcitabine and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving durvalumab with gemcitabine and cisplatin before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed in patients with high risk resectable cholangiocarcinoma.

Detailed description

PRIMARY OBJECTIVE: I. To examine the proportion of patients who complete neoadjuvant therapy followed by curative intent surgical resection. SECONDARY OBJECTIVES: I. To determine the major pathologic response (MPR) rate. (Efficacy) II. To determine the proportion of patients who attain an R0 resection following neoadjuvant therapy. (Efficacy) III. To determine the radiological response rate after 2 and 4 cycles of neoadjuvant therapy. (Efficacy) IV. To determine the overall survival of patients receiving neoadjuvant therapy prior to curative intent surgical resection. (Efficacy) V. To determine the relapse free survival (RFS) of patients receiving neoadjuvant therapy prior to curative intent surgical resection. (Efficacy) VI. To estimate the incidence of adverse events during neoadjuvant therapy which would preclude completion of the neoadjuvant chemotherapy regiment as defined by grade 4 or above adverse events by Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0. (Feasibility) VII. To determine the proportion of patients who are able to start adjuvant therapy within 10 weeks of surgical resection. (Feasibility) VIII. To determine the proportion of patients who can complete 4 cycles of adjuvant therapy. (Feasibility) IX. To determine the efficacy of therapy in different molecular subtypes (by deoxyribonucleic acid \[DNA\] profiling, ribonucleic acid \[RNA\] profiling, and circulating tumor \[ct\]DNA-based minimal residual disease \[MRD\]). (Toxicity Profiles and Biomarkers) X. To compare pre- and post-neoadjuvant therapy changes in the phenotypic profiles of circulating immune cells. (Toxicity Profiles and Biomarkers) XI. To correlate ctDNA-based MRD, tissue and blood based immune biomarkers, and body composition with the primary/secondary endpoints. (Toxicity Profiles and Biomarkers) EXPLORATORY OBJECTIVES: I. Quantitative European Association for the Study of the Liver (qEASL)-based 3 dimensional (3D) enhancement measurement will be used as a surrogate marker of pathological response. II. The primary and secondary outcomes will be associated with the visceral abdominal fat, subcutaneous abdominal fat, and muscle at the level of L2/L3. OUTLINE: Patients receive durvalumab intravenously (IV) over 60 minutes on day 1 with gemcitabine IV over 30 minutes and cisplatin IV over 60 minutes on days 1 and 8 for 4 cycles and then undergo surgical resection on study. Following surgery, patients may continue the durvalumab, gemcitabine and cisplatin regimen for up to 4 additional cycles. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo computed tomography (CT) scans and/or magnetic resonance imaging (MRI) scans and blood sample collection throughout study, as well as tissue biopsies during screening and on study. After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 5 years and then yearly.

Conditions

• Resectable Intrahepatic Cholangiocarcinoma

Interventions

Type	Name	Description
PROCEDURE	Biopsy Procedure	Undergo tissue biopsy
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
DRUG	Cisplatin	Given IV
PROCEDURE	Computed Tomography	Undergo CT scan
BIOLOGICAL	Durvalumab	Given IV
DRUG	Gemcitabine	Given IV
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI scan
PROCEDURE	Resection	Undergo surgical resection

Timeline

• Start date: 2024-07-10
• Primary completion: 2027-02-12
• Completion: 2027-02-12
• First posted: 2023-09-22
• Last updated: 2026-04-17

Locations

58 sites across 1 country: United States

Regulatory

• FDA-regulated drug study