Clinical trial NCT05036798: Tislelizumab+Lenvatinib+Gemox Regiment for Potentially Resectable Locally Advanced Malignant Tumors of Biliary System.
Official title: 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 type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Potentially Resectable Locally Advanced Malignant Tumors of Biliary System
Lead sponsor: Tianjin Medical University Cancer Institute and Hospital
Sponsor class: OTHER
First posted: 2021-09-08
Enrollment: 30
Sex: ALL
Minimum age (years): 20
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

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   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.

Primary outcomes:
measure: R0 resection rate
timeFrame: 5 months
Secondary outcomes:
measure: Progression-free survival (PFS)
timeFrame: 18 months
measure: Disease control rate (DCR)
timeFrame: 5 months
measure: Objective response rate (ORR)
timeFrame: 5 months
measure: Overall survival (OS)
timeFrame: 24 months
measure: Improvement in quality of life as measured by the EORTC Quality of Life Questionnaire QLQ-C30 (V3.0)
timeFrame: 24 months
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute & Hospital
state: Tianjin
Study officials:
References: