Tislelizumab Combined With Lenvatinib and GEMOX Versus Tislelizumab Combined With GEMOX in Conversion Therapy of ICC and GBC.

Study Overview
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Brief Summary
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This is an Open Phase II Clinical Study of Tislelizumab Combined with Lenvatinib and GEMOX Versus Tislelizumab Combined with GEMOX in the Treatment of Locally Advanced Intrahepatic Cholangiocarcinoma and Gallbladder Cancer.

Official Title
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An Open Phase II Clinical Study of Tislelizumab Combined With Lenvatinib and GEMOX Versus Tislelizumab Combined With GEMOX in the Treatment of Locally Advanced Intrahepatic Cholangiocarcinoma and Gallbladder Cancer.

Conditions
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Potentially Resectable Locally Advanced Intrahepatic Cholangiocarcinoma and Gallbladder Cancer

Intervention / Treatment
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* Drug: tislelizumab+lenvatinib+GMOX
* Drug: tislelizumab+GEMOX


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1：Intrahepatic cholangiocarcinoma and gallbladder carcinoma confirmed by histology or cytology. Potential resectable criteria: The first stage R0 resection cannot be guaranteed for patients with cholangiocarcinoma admitted to our hospital, and there are the following imaging characteristics (satisfy one or more) The hilar and retroperitoneal lymph nodes were considered for metastasis but could be resected completely. Intrahepatic cholangiocarcinoma has multiple foci, but foci are less than three and limited to half of the liver. Local progression of gallbladder carcinoma with colon or duodenal involvement. Hilar cholangiocarcinoma or lower segment of cholangiocarcinoma involving portal vein or hepatic artery requires combined vascular resection or reconstruction. 2. Patient age: 20-79 years 3. At least one measurable lesion as defined in RECIST version 1.1 4. ECOG score was 0-1 5.Life expectancy of at least 90 days 6.Aspartic aminotransferase and alanine aminotransferase ≤150 IU/L in patients with bile drainage, and ≤100IU/L in patients without bile drainage Total bilirubin ≤3.0 mg/dL in patients with bile drainage and ≤2.0 mg/dL in patients without bile drainage. 7.Creatinine ≤1.5 mg/dL was used in the single treatment cohort and ≤1.2 mg/dL was used in the combination treatment cohort; Creatinine clearance [measured or estimated using the Cockcroft-Gault equation]≥45mL/min for the single treatment cohort and ≥50mL/min for the combination treatment cohort 8.Neutrophil ≥1500 cells /µL, hemoglobin ≥9.0g/dL, platelet ≥100000/µL 9.PD-L1 expression analysis and microsatellite unstable state analysis were performed on tumor tissue samples. Exclusion Criteria: Previous treatment with tislelizumab or anti-PD-1, PD-L1, PD-L2, CD137, CTLA-4 antibody, or any other therapy that regulates T cells Received systemic corticosteroid or immunosuppressive therapy within 28 days before inclusion Concurrent autoimmune diseases or a history of chronic or recurrent autoimmune diseases A history of pleural adhesions or pericardium adhesions within 28 days prior to inclusion Test positive for HIV antibody, human T-cell leukemia virus type 1 antibody, hepatitis C virus antibody, hepatitis B surface protein antigen, hepatitis B surface protein antibody, hepatitis B core protein antibody or any detectable hepatitis B virus DNA Multiple primary cancers (except completely resected basal cell carcinoma, stage I squamous cell carcinoma, carcinoma in situ, intramucosal carcinoma, and superficial bladder carcinoma, and any other cancer that has not recurred for at least 5 years) Brain or meningeal metastases (unless asymptomatic and do not require treatment) and uncontrolled or severe cardiovascular disease.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 79 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: tislelizumab+lenvatinib+GMOX<br>tislelizumab 200mg, Q3W, lenvatinib 8mg/kg, PO, qd, gemcitabine 1g/㎡, D1, D8, Q3W, oxaliplatin 100mg/㎡, D1, Q3W. Imaging evaluation was performed after 3 cycles. Patients who met surgical criteria will receive R0 resection and adjuvant therapy 4-8 weeks after surgery (tislelizumab 200mg, Q3W, lenvatinib 8mg/kg, PO, qd) for one year or until disease progression or toxicity became intolerable. Inoperable patients continue to receive ≤4 cycles of treatment, imaging evaluation every two cycles. Patients will receive R0 resection if meet surgical criteria and adjuvant therapy 4-8 weeks after surgery (Tislelizumab 200mg, Q3W, lenvatinib 8mg/kg, PO, qd,) for one year or until disease progression or toxicity became intolerable. Patients still unable to receive surgery, the experimental group will receive tislelizumab 200mg, Q3W, lenvatinib 8mg/kg, PO, qd for maintained treatment until disease progression or toxicity became intolerable. | Drug: tislelizumab+lenvatinib+GMOX<br>* tislelizumab 200mg, Q3W Lenvatinib 4mg Po QD Gemcitabine 1g/m2 Oxaliplatin 100mg/m, D1, q3W2<br>|
| Active Comparator: tislelizumab+GEMOX<br>tislelizumab 200mg, Q3W, gemcitabine 1g/㎡, D1, D8, Q3W, oxaliplatin 100mg/㎡, D1, Q3W. Imaging evaluation was performed after 3 cycles. Patients who met surgical criteria will receive R0 resection and adjuvant therapy 4-8 weeks after surgery (tislelizumab 200mg, Q3W) for one year or until disease progression or toxicity became intolerable. Inoperable patients continue to receive ≤4 cycles of treatment, imaging evaluation every two cycles. Patients will receive R0 resection if meet surgical criteria and adjuvant therapy 4-8 weeks after surgery (Tislelizumab 200mg, Q3W) for one year or until disease progression or toxicity became intolerable. Patients still unable to receive surgery, the experimental group will receive tislelizumab 200mg, Q3W for maintained treatment until disease progression or toxicity became intolerable. | Drug: tislelizumab+GEMOX<br>* tislelizumab+GEMOX<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) |  | 18 months | 
| Overall survival (OS) |  | 24 months | 
| R0 resection rate |  | 6 months | 
| AE | Improvement in quality of life as measured by the EORTC Quality of Life Questionnaire QLQ-C30 (V3.0) | 24 months |