A Phase I/II Study of Anti-PD-1/PD-L1 Antibodies in Combination With Gemcitabine and Cisplatin for Patients With Advanced Cholangiocarcinoma
Overview
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Shanghai Zhongshan Hospital
- Enrollment
- 50
- Locations
- 1
- Primary Endpoint
- Incidence of adverse events
Overview
Brief Summary
This study is a prospective, observational study designed to analyze the safety, tolerability, and efficacy of first-line treatment using the combination of gemcitabine and cisplatin plus anti-PD-1/PD-L1 antibodies for patients with advanced cholangiocarcinoma.
Detailed Description
This is a prospective cohort study of combination anti-PD-1/PD-L1 antibodies plus Gemcitabine and Cisplatin chemotherapy for adult patients (≥18) with advanced cholangiocarcinoma
Gemcitabine and Cisplatin (GC): This chemotherapy doublet has been the historical standard of care for advanced cholangiocarcinoma. It works by interfering with DNA synthesis and causing DNA cross-linking, leading to tumor cell apoptosis.
Anti-PD-1/PD-L1 antibodies: Immunotherapy (including pembrolizumab, durvalumab, envafolimab, tislelizumab, etc.) is designed to block the PD-1/PD-L1 immune checkpoint pathway, thereby reinvigorating T-cells to recognize and attack tumor cells. Recent pivotal trials (e.g., TOPAZ-1, KEYNOTE-966) have demonstrated that adding immunotherapy to GC chemotherapy significantly improves overall survival compared to chemotherapy alone.
This study aims to evaluate the real-world safety, tolerability, and clinical efficacy of this combination regimen in specific clinical practice settings for unresectable late-stage cholangiocarcinoma patients.
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 18 Years to 90 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •1\. ≥18 years old, male or female
- •Histologically or cytologically confirmed locally advanced or metastatic biliary tract cancer (including ICC, ECC, or GBC) that is not amenable to curative surgery or local therapies.
- •3\. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
- •Patient has given written informed consent.
- •The function of important organs meets the requirements
- •Expected survival ≥12 weeks
- •Non-surgical sterilization or women of childbearing age need to use a medically-accepted contraceptive (such as an intrauterine device, contraceptive or condom) during the study period and within 3 months after the end of the study treatment period.
Exclusion Criteria
- •1\. The patient has any active autoimmune disease or a history of autoimmune disease (such as the following, but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, nephritis, thyroid Hyperfunction; patients with vitiligo; complete remission of asthma in childhood, can be included without any intervention after adulthood; asthma patients who require bronchodilators for medical intervention cannot be included);
- •The patient is using immunosuppressive agents or systemic hormonal therapy to achieve immunosuppressive purposes (agents amount \> 10 mg / day of prednisone or other therapeutic hormones), and continue to use within 2 weeks before enrollment;
- •Have clinical symptoms or disease that are not well controlled;
- •Significant clinically significant bleeding symptoms or a clear bleeding tendency within 3 months prior to randomization;
- •Arterial/venous thrombosis in the first 6 months of randomization
- •According to the investigator, the patient has other factors that may affect the results of the study or lead to the termination of the study, such as alcohol abuse, drug abuse, other serious diseases (including mental illness) requiring combined treatment, and serious laboratory abnormalities.#with family or social factors, it will affect the safety of patients.
- •Known hypersensitivity to Gemcitabine, Cisplatin, or platinum-containing compounds; significant hearing impairment (grade ≥2) or peripheral neuropathy (grade ≥2) that contraindicates Cisplatin;
Arms & Interventions
Chemotherapy plus Immunotherapy Combination
Intervention: Anti-PD-1/PD-L1 antibody (Drug)
Chemotherapy plus Immunotherapy Combination
Intervention: Gemcitabine and Cisplatin Chemotherapy (Drug)
Outcomes
Primary Outcomes
Incidence of adverse events
Time Frame: Up to 30 days after last treatment dose
Safety will be monitored by addressing and recording all adverse events (AEs), serious adverse events (SAEs) and specific laboratory abnormalities (worst grade). Toxicities will be graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0.
Objective response rate(ORR)
Time Frame: 5 years
Evaluated by researchers based on the RECIST 1.1 standard
Progression free survival(PFS)
Time Frame: 5 years
Evaluated by researchers based on the RECIST 1.1 standard
To the relief time (TOR)
Time Frame: Time Frame: 5 years
Evaluated by researchers based on the RECIST 1.1 standard
Duration of relief(DOR)
Time Frame: 5 years
Evaluated by researchers based on the RECIST 1.1 standard
Disease Control Rate (DCR)
Time Frame: Time Frame: 5 years
Evaluated by researchers based on the RECIST 1.1 standard
Secondary Outcomes
No secondary outcomes reported