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

NCT ID: NCT05620498

Last Updated: 2022-11-17

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-09-08
• Study Completion Date: 2024-03-31

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.

Conditions

Potentially Resectable Locally Advanced Intrahepatic Cholangiocarcinoma and Gallbladder Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

tislelizumab+lenvatinib+GMOX

Intervention Type: DRUG

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

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.

Group Type: ACTIVE_COMPARATOR

tislelizumab+GEMOX

Intervention Type: DRUG

tislelizumab+GEMOX

Interventions

tislelizumab+lenvatinib+GMOX

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

Intervention Type: DRUG

tislelizumab+GEMOX

tislelizumab+GEMOX

Intervention Type: DRUG

Eligibility Criteria

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)

1. The hilar and retroperitoneal lymph nodes were considered for metastasis but could be resected completely.

2. Intrahepatic cholangiocarcinoma has multiple foci, but foci are less than three and limited to half of the liver.

3. Local progression of gallbladder carcinoma with colon or duodenal involvement.

4. 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

1. Previous treatment with tislelizumab or anti-PD-1, PD-L1, PD-L2, CD137, CTLA-4 antibody, or any other therapy that regulates T cells

2. Received systemic corticosteroid or immunosuppressive therapy within 28 days before inclusion

3. Concurrent autoimmune diseases or a history of chronic or recurrent autoimmune diseases

4. A history of pleural adhesions or pericardium adhesions within 28 days prior to inclusion

5. 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

6. 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)

7. Brain or meningeal metastases (unless asymptomatic and do not require treatment)

8. and uncontrolled or severe cardiovascular disease.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 79 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tianjin Medical University Cancer Institute and Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Tianjin Medical University Cancer Institute & Hospital

Tianjin, Tianjin Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

huikai Li, Doctor

Role: CONTACT

tjchlhk@126.com

18622228639

Dongming Liu, Doctor

Role: CONTACT

18502261477

Facility Contacts

Huikai Li, MD

Role: primary

lihuikai@tjmuch.com

+862223340123 ext. 3091

Other Identifiers

2209001086

Identifier Type: -

Identifier Source: org_study_id