Tislelizumab+Lenvatinib+Gemox Regiment for Potentially Resectable Locally Advanced Malignant Tumors of Biliary System.

A Single-arm, Open, Phase II Clinical Study of Tislelizumab Combined With Lenvatinib and Gemox Regimen for Transformational Treatment of Potentially Resectable Locally Advanced Malignant Tumors of Biliary System.

This is a single-arm, open, Phase II clinical study of Tislelizumab combined with lenvatinib and Gemox regimen for transformational treatment of potentially resectable locally advanced malignant tumors of biliary system.

Study Overview

• Status: Active, not recruiting
• Conditions: Potentially Resectable Locally Advanced Malignant Tumors of Biliary System
• Intervention / Treatment: Drug: Tislelizumab

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Tianjin Medical University Cancer Institute & Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 1. Histological diagnosis of potentially resectable local advanced biliary malignancies (intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder carcinoma, ampullary carcinoma);

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. No prior medical treatment; 6. Adequate organ and bone marrow function and laboratory tests meet the following requirements:

   1. HGB≥90g/L；
   2. NEUT≥1.5×109/L；
   3. PLT ≥100×109/L；
   4. TBIL≤1.5 times normal upper limit (ULN);
   5. ALT and AST ≤2.5 x ULN;ALT and AST≤5×ULN for liver metastasis;
   6. Endogenous creatinine clearance ≥50ml/min (Cockcroft-Gault formula);
   7. Urinary protein < (++), or 24 hours urinary protein <1.0 g; 7. Coagulation was normal without active bleeding
   1. International standardized ratio INR≤1.5;

   2. Partial thrombin time APTT≤1.5 ULN; 8. Women of childbearing age must have a negative pregnancy test (serum or urine) within 14 days prior to enrollment and voluntarily use an appropriate method of contraception during the observation period and within 8 weeks after the last administration of the study drug;For men, surgical sterilization or consent to use appropriate methods of contraception during the observation period and for 8 weeks after the last administration of the study drug; 9. Estimated survival ≥3 months; 10. The patients voluntarily participated in the study and signed the informed consent (ICF); 11. It is expected that patients with good compliance will be able to follow up the efficacy and adverse reactions according to protocol requirements.

      12. Tumor tissue samples for PD-L1 expression analysis and microsatellite instability analysis.

      Exclusion Criteria:

      - The patient must be excluded from the study if any of the following conditions occur at the time of inclusion:

      1. Allergic to known anti-PD-1 and anti-PD-L1 antibodies; 2. Patients with hypertension (systolic blood pressure >140 mmHg, diastolic blood pressure >90 mmHg), grade I or above coronary heart disease, grade I arrhythmia (including prolonged QTc interval > 450 ms in males and > 470 ms in females) and grade I cardiac insufficiency; 3. Risk of biliary obstruction; 5. Allergic to the drugs of the program (gemcitabine, oxaliplatin); 6. Patients with a clear tendency of gastrointestinal bleeding, including the following conditions: local active ulcer lesions, and fecal occult blood (++) cannot be included in the group; Patients with a history of melena and hematemesis within 1 month; 7. Patients with immune system diseases need to take more than 10mg of dexamethasone daily; 8. Patients with concomitant diseases that, according to the judgment of the investigator, seriously endanger the patient's safety or affect the patient's ability to complete the study; 9. The researcher considered it unsuitable for inclusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Tislelizumab combined with Lenvatinib and GEMOX; Chemotherapy regimen(GEMOX): Gemcitabine 1g/m2,Oxaliplatin 100mg/m, D1, Q3W Tislelizumab 200mg D1 Q3w Lenvatinib 4mg Po QD Receive at least 3 cycles of combined treatment, and perform imaging evaluation after 3 cycles of treatment. If surgical treatment is not possible, imaging evaluation will be performed every two cycles thereafter until surgical treatment is feasible. If more than 7 cycles are still not possible for surgical resection, enter Tislelizumab + Lenvatinib maintenance treatment until the disease progresses or the toxicity cannot be tolerated. If patients undergoing R0 resection, start to receive Tislelizumab + Lenvatinib+Gemox regimen in 4-8 weeks after surgery for 7 cycles, and then entered Tislelizumab+Lenvatinib for 1 year or disease progression or toxicity cannot be tolerated

Drug: Tislelizumab; Chemotherapy regimen: Gemcitabine 1g/m2 Oxaliplatin 100mg/m, D1, q3W2 Tislelizumab 200mg D1 Q3w Lenvatinib 4mg Po QD; Other Names: Lenvatinib; Gemox

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
R0 resection rate	5 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival (OS)	24 months
Progression-free survival (PFS)	18 months
Disease control rate (DCR)	5 months
Objective response rate (ORR)	5 months
Improvement in quality of life as measured by the EORTC Quality of Life Questionnaire QLQ-C30 (V3.0)	24 months

Collaborators and Investigators

• Sponsor: Tianjin Medical University Cancer Institute and Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2021
• Primary Completion (Actual): July 2, 2022
• Study Completion (Anticipated): December 30, 2023

Study Registration Dates

• First Submitted: August 31, 2021
• First Submitted That Met QC Criteria: September 6, 2021
• First Posted (Actual): September 8, 2021

Study Record Updates

• Last Update Posted (Actual): September 7, 2022
• Last Update Submitted That Met QC Criteria: September 4, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Lenvatinib
• Other Study ID Numbers: GDS20210220320615

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No