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

Sponsor

Tianjin Medical University Cancer Institute and Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT05620498

Collaborator

(none)

Enrollment

Location

Arms

18.7

Anticipated Duration (Months)

3.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Potentially Resectable Locally Advanced Intrahepatic Cholangiocarcinoma and Gallbladder Cancer	Drug: tislelizumab+lenvatinib+GMOX Drug: tislelizumab+GEMOX	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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.

Actual Study Start Date :

Sep 8, 2022

Anticipated Primary Completion Date :

Jun 30, 2023

Anticipated Study Completion Date :

Mar 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: tislelizumab+lenvatinib+GMOX 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 tislelizumab 200mg, Q3W Lenvatinib 4mg Po QD Gemcitabine 1g/m2 Oxaliplatin 100mg/m, D1, q3W2
Active Comparator: tislelizumab+GEMOX 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 tislelizumab+GEMOX

Arm

Intervention/Treatment

Experimental: tislelizumab+lenvatinib+GMOX

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

tislelizumab 200mg, Q3W Lenvatinib 4mg Po QD Gemcitabine 1g/m2 Oxaliplatin 100mg/m, D1, q3W2

Active Comparator: tislelizumab+GEMOX

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

tislelizumab+GEMOX

Outcome Measures

Primary Outcome Measures

Objective response rate (ORR) [6 months]

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 79 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Tianjin Medical University Cancer Institute & Hospital	Tianjin	Tianjin	China	300060

Sponsors and Collaborators

Tianjin Medical University Cancer Institute and Hospital

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Tianjin Medical University Cancer Institute and Hospital

ClinicalTrials.gov Identifier:

NCT05620498

Other Study ID Numbers:

2209001086

First Posted:

Nov 17, 2022

Last Update Posted:

Nov 17, 2022

Last Verified:

Nov 1, 2022

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Cholangiocarcinoma

Gallbladder Neoplasms

Lenvatinib

Study Results

No Results Posted as of Nov 17, 2022