NCT06567600

Low-dose Gemcitabine and Cisplatin and PD-1/PD-L1 Antibody Therapy in Intrahepatic Cholangiocarcinoma

Combined Therapy Using Low-dose Gemcitabine and Cisplatin Chemotherapy and PD-1/PD-L1Antibody for Patients With Advanced and Unresectable Intrahepatic Cholangiocarcinoma: an Open-label, Multicenter, Single-arm Clinical Trial

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 43 (estimated)
• Sponsor: Third Affiliated Hospital, Sun Yat-Sen University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

In this phase 2 study, researchers aimed to evaluate the efficacy and safety of low-dose gemcitabine and cisplatin chemotherapy and the immune checkpoint inhibitor PD-1/PD-L1 antibody in patients with advanced and unresectable intrahepatic cholangiocarcinoma.

Detailed description

More and more studies suggest that low-dose chemotherapy has the ability to reshape the tumor microenvironment and promote tumor immunotherapy in a variety of tumors, supporting the rationality of combining low-dose chemotherapy with immunotherapy to effectively treat tumors with low T cell infiltration. More than half of intrahepatic cholangiocarcinomas are non-inflammatory \"cold tumors\", and their unique immunosuppressive microenvironment is one of the reasons for the poor response rate to immunotherapy. Low-dose chemotherapy can transform \"cold\" tumors with low immunogenicity and poor immune cell infiltration into \"hot\" tumors with immune responsiveness and sufficient immune cell infiltration, enhance the effect of ICIs on tumor cells, and minimize systemic toxicity, thus preserving a \"therapeutic window\" for combined immunotherapy/targeted therapy. Preclinical and clinical studies have shown that it is necessary to study the optimal dose of chemotherapeutic drugs in combination therapy. In combination therapy, long-term, adequate doses of chemotherapeutic drugs may be unnecessary because this will not only lead to more severe toxicity, but also damage rather than enhance anti-tumor immunity. To determine the efficacy and safety of low-dose chemotherapy combined with PD-1/PD-L1 inhibitors in the treatment of patients with advanced intrahepatic cholangiocarcinoma, we designed an open-label, prospective, multicenter, single-arm clinical study of low-dose gemcitabine + cisplatin combined with PD-1/PD-L1 inhibitors in the treatment of patients with advanced intrahepatic cholangiocarcinoma.

Conditions

• Intrahepatic Cholangiocarcinoma
• Chemotherapy Effect
• Immunotherapy

Interventions

Type	Name	Description
DRUG	Low-dose Gemcitabine and Cisplatin Chemotherapy plus PD-1/PD-L1Antibody	Low-dose Gemcitabine and Cisplatin Chemotherapy: Gemcitabine 500 mg/m2 Cisplatin 12.5 mg/m2 on day 1 and day 8 of each 21-day cycle for up to eight cycles PD-1/PD-L1Antibody: Pembrolizumab 200mg on day 1 of each 21-day cycle Durvalumab 1500 mg on day 1 of each 21-day cycle After completion of gemcitabine and cisplatin, 200mg of Pembrolizumab or 1500 mg of Durvalumab may administer once every 3 or 4 weeks until clinical or imaging (per RECIST v1.1) disease progression or until unacceptable toxicity, withdrawal of consent, or any other discontinuation criteria were met.

Timeline

• Start date: 2024-09-01
• Primary completion: 2027-12-31
• Completion: 2028-12-31
• First posted: 2024-08-22
• Last updated: 2024-08-22

Locations

1 site across 1 country: China