GEMOX Combined With Targeted Therapy and Immunotherapy for Patients With Advanced Cholangiocarcinoma

Study Overview
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Brief Summary
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The clinical trial is designed to evaluate the safety and efficacy of GEMOX combined with targeted therapy and immunotherapy for patients with advanced cholangiocarcinoma, and screen the potential biomarkers

Official Title
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Efficacy, Safety Evaluation and Biomarker Screening of GEMOX Combined With Targeted Therapy and Immunotherapy for Patients With Advanced Cholangiocarcinoma

Conditions
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Cholangiocarcinoma

Intervention / Treatment
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* Drug: GEMOX Regimen
* Drug: Lenvatinib
* Drug: Toripalimab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, 18 years old ≤ age ≤ 70 years old ECOG PS scores 0-1 Expected survival time > 12 weeks Advanced cholangiocarcinoma confirmed by histopathology and/or cytology, locally advanced (inoperable) or distant metastasis, and with at least one measurable lesion that has not been locally treated (per RECIST 1.1 criteria) Not received any previous systemic or local treatment for the tumor Sufficient organ and bone marrow function Exclusion Criteria: Suffered from other malignant tumors in the past 5 years (except Radical basal cell carcinoma of the skin squamous carcinoma of the skin and/or radical resected carcinoma in situ) Ampullary tumor Received treatment from other clinical trials within 4 weeks before the first dose Received any anti-PD-1 antibody, anti-PD-L1/L2 antibody, anti-CTLA4 antibody, or other immunotherapy Suffered from severe cardiovascular disease within 12 months before enrollment, such as symptomatic coronary heart disease, congestive heart failure ≥ Grade II, uncontrolled arrhythmia, and myocardial infarction Uncontrollable pleural effusion, pericardial effusion or ascites Use steroids or other systemic immunosuppressive therapies 4 weeks before enrollment Allergic reactions to the drugs used in this study HIV antibody positive, active hepatitis B or C (HBV, HCV) Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation other conditions that the investigator deems inappropriate for enrollment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: group 1<br>Lenvatinib+Toripalimab | Drug: Lenvatinib<br>* 8/12mg PO QD continuously<br>Drug: Toripalimab<br>* 240mg IV d1 Q3W<br>|
| Experimental: group 2<br>GEMOX+Lenvatinib+Toripalimab | Drug: GEMOX Regimen<br>* Oxaliplatin 100mg/m2 IV d1 Q3W+ gemcitabine 1000mg/m2 IV d1/8 Q3W<br>Drug: Lenvatinib<br>* 8/12mg PO QD continuously<br>Drug: Toripalimab<br>* 240mg IV d1 Q3W<br>|
| Experimental: group 3<br>Lenvatinib+Toripalimab (failure of GEMOX treatment) | Drug: Lenvatinib<br>* 8/12mg PO QD continuously<br>Drug: Toripalimab<br>* 240mg IV d1 Q3W<br>|
| Experimental: group 4<br>GEMOX+Toripalimab | Drug: GEMOX Regimen<br>* Oxaliplatin 100mg/m2 IV d1 Q3W+ gemcitabine 1000mg/m2 IV d1/8 Q3W<br>Drug: Toripalimab<br>* 240mg IV d1 Q3W<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) | Overall response rate ( ORR) is defined as proportion of participants who have a best response of CR or PR | up to 90 days after last treatment administration | 
| The frequency, duration, and severity of adverse events | Safety is assessed by the frequency, duration, and severity of adverse events | up to 30 days after last treatment administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Control Rate (DCR) | Disease Control Rate (DCR) is defined as proportion of participants who have a best response of CR、PR or SD | up to 90 days after last treatment administration | 
| Progression free survival (PFS) | the time period from randomization of the participants to objective tumor progression or death | up to 3 years | 
| Overall survival (OS) | the time period from the randomization of the participants to the death event due to any reason | up to 3 years |