Camrelizumab Plus Apatinib in Combination With GEMOX (Gemcitabine and Oxaliplatin ) in Patients With Locally Advanced Biliary Tract Cancer

Study Overview
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Brief Summary
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This is a phase II open-label, one-arm, multicenter study aimed to explore the efficacy and safety of perioperative (neoadjuvant and adjuvant) treatment for patients with advanced biliary tract carcinoma.

Detailed Description
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Enrolled participants should be treated with neoadjuvant camrelizumab and apatinib and GEMOX, after surgery, be treated with adjuvant camrelizumab and tegafur.

Official Title
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Camrelizumab Plus Apatinib Combined With GEMOX (Gemcitabine and Oxaliplatin ) in the Perioperative Treatment of Locally Advanced Biliary Tract Malignancies: A Prospective, Multicenter, Phase Ⅱ Study

Conditions
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Advanced Biliary Tract Carcinoma

Intervention / Treatment
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* Drug: Camrelizumab, apatinib, gemcitabine, oxaliplatin, tegafur


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent document must be signed. Aged 18-75 years old, both genders. Pathologically confirmed biliary tract adenocarcinoma and haven't been treated before. An Eastern Cooperative Oncology Group performance status of 0 to 1. Locally advanced biliary tract adenocarcinoma confirmed by MDT discussion. The function of vital organs meets the following requirements: the blood ANC count≥1.5x109 /L; hemoglobin ≥ 90 g/L，the blood platelet count≥80 x109 /L, total bilirubin ≤ 1.5 x ULN, ALT and AST ≤3 x ULN(< 5 x ULN for patients with live metastasis), serum creatinine≤1.5 x ULN, endogenous creatinine clearance rate ≥45ml/min. At least 1 measurable lesion as defined by RECIST 1.1. Women of reproductive age need to take effective contraceptive measures during and within 3 months of the end of medication. Subjects should have good compliance and cooperate with the follow-up. Exclusion Criteria: Subject has any active autoimmune disease or history of autoimmune disease will not be included, nor will patients with active tuberculosis or hepatitis or HIV. Subjects with illness or medical conditions that could jeopardize their sugery, such as severe cardiopulmonary insufficiency and coagulation disorders, cannot be enrolled. Subjects with active malignancies other than BTC within 5 years should be excluded, except for cured basal cell carcinoma of the skin and carcinoma in situ of the cervix and superficial bladder cancer [Ta, Tis & T1] and papillary thyroid cancer. Any unstable systemic disease which might need systemic treatment should not be enrolled (including active infection, liver or renal disease, metabolic disease, acute cerebral infarction or hemorrhage), or serious co-morbidities that by the judgment of the investigator, may compromise the patient's safety or impair the patient's ability to complete the study. Subjects who have significant cardiovascular events should not be enrolled, for example: congestive heart failure > NYHA class 2, unstable angina, active coronary artery disease (CAD) (only allow the subjects with presence of myocardial infarction more than 1 year prior to study); severe arrhythmias in need of treatment (only allow those been treated with β-blockers or digoxin) or uncontrolled hypertension. Subjects with history of neurological or psychiatric disease, including epilepsy or dementia or diseases alike should not be enrolled. Subjects with interstitial lung disease or a history of interstitial pneumonia should not be enrolled. Subjects who had participated in other anti-tumor clinical trials within 4 weeks prior to enrollment should be avoided. Subjects who had used PD-1/PD-L1 or other antitumor immunotherapeutic agents prior to enrollment should be avoided. The following subjects should be avoided: pregnant or lactating women; those who have childbearing potential and unwilling or unable to use effective contraception measures. Other circumstances that could affect the trial or the result of the study judged by the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: treatment arm<br> | Drug: Camrelizumab, apatinib, gemcitabine, oxaliplatin, tegafur<br>* Perioperative treatment: camrelizumab plus apatinib in combination with GEMOX 2-4 cycles (neoadjuvant); camrelizumab plus tegafur up to 1 year (adjuvant).<br>* Other names: surgery;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| R0 resection rate | The proportion of patients with negative resection margin among patients undergoing surgery | up to 2 years | 
| 1-year event-free survival (EFS) rate | The proportion of patients with first documented recurrence or disease progression as determined by the investigator, or death from any cause, whichever occurs first. | up to 1 year |