Adjuvant Immunotherapy Combined With Chemoradiation for Patients With High-risk reseCtable Extrahepatic chOlangiocaRcinoma and gallblaDder Cancer

Study Overview
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Brief Summary
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The study is a multicenter phase II randomized controlled trial. The purpose is to investigate the efficacy and safety of adjuvant immunotherapy combined with chemoradiation for patients with high-risk resectable extrahepatic cholangiocarcinoma and gallbladder cancer.

Detailed Description
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The trial will recruit 92 patients, and they will be randomized (1:1) into two groups (chemoradiation+immunotherapy group, observation group) after operation. Patients in chemoradiation+immunotherapy group will receive camrelizumab 200mg intravenously every 3 weeks until clinical or radiographic disease progression, unacceptable toxicity, death, termination of the study or withdrawal. After 1 or 2 courses of camrelizumab, patients went on to receive capecitabine (1,330 mg/m2 per day, in divided doses twice daily, 7 days per week) concurrent with radiotherapy (45 Gy to regional lymph nodes and 54 to 59.4 Gy to preoperative tumor bed). Patients in observation group will not receive any anti-cancer therapy.

Official Title
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Adjuvant Immunotherapy Combined With Chemoradiation for Patients With High-risk reseCtable Extrahepatic chOlangiocaRcinoma and gallblaDder Cancer: a Phase II, Multicenter, Randomized Controlled Trial

Conditions
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Biliary Tract Cancer, Extrahepatic Cholangiocarcinoma, Gallbladder Cancer

Intervention / Treatment
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* Drug: Chemotherapy
* Other: Observation
* Procedure: Immunotherapy
* Radiation: Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 18-70 years; Primary resectable extrahepatic cholangiocarcinoma and gallbladder cancer proved by pathology which underwent radical surgery; Pathology indicates R0 with T2-4 or N1; or R1; ECOG PS 0-1; Adequate hematologic, hepatic and renal function: ANC ≥ 1.5x10^9/L, Hb ≥ 80g/L, PLT ≥ 100 x10^9/L, albumin ≥ 28g/L, total bilirubin < 1.5×ULN, ALT and AST < 2.5×ULN, CREA<1.5×ULN; At least 6 months of life expectancy. Exclusion Criteria: Pregnant or breastfeeding women, or expecting to conceive or father children within the projected duration of the trial; Received previous anti-cancer therapies; With purulent, infected or delayed healed wounds; Have risky bleeding events requiring transfusion, operation or local therapies, continuous medication in the past 3 months; Have thromboembolism in the past 6 months, including myocardial infarction, unstable angina, stroke or transient ischemic attack, pulmonary embolism, deep vein thrombosis; Have taken aspirin (>325mg/day) or other antiplatelet drugs continuously for 10 days or more within 2 weeks before enrolment; Uncontrollable hypertension, systolic pressure>140mmHg or diastolic pressure>90mmHg after best medical care, or history of hypertensive crisis or hypertensive encephalopathy; Symptomatic congestive heart failure (NYHA class II-IV). Symptomatic or badly-controlled arrhythmia. Congenital long QT syndrome or modified QTc>500ms upon screening; Have active autoimmune diseases that require systemic treatment within 2 years before enrolment; Active tuberculosis, having antituberculosis therapy at present or within 1 year; Have a known history of prior invasive malignancies within 5 years before enrolment; Have other uncontrollable comorbidities; Infection of HIV, known syphilis requiring treatment; Allergic to chemotherapeutics.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>Patients in treatment group will receive camrelizumab 200mg intravenously every 3 weeks until clinical or radiographic disease progression, unacceptable toxicity, death, termination of the study or withdrawal. After 1 or 2 courses of camrelizumab, patients went on to receive capecitabine (1,330 mg/m2 per day, in divided doses twice daily, 7 days per week) concurrent with radiotherapy (45 Gy to regional lymph nodes and 54 to 59.4 Gy to preoperative tumor bed). | Drug: Chemotherapy<br>* Capecitabine (1,330 mg/m2 per day, in divided doses twice daily, 7 days per week).<br>Procedure: Immunotherapy<br>* Camrelizumab 200mg intravenously every 3 weeks until clinical or radiographic disease progression, unacceptable toxicity, death, termination of the study or withdrawal.<br>Radiation: Radiotherapy<br>* 45 Gy to regional lymph nodes and 54 to 59.4 Gy to preoperative tumor bed.<br>|
| Placebo Comparator: Observation<br>Patients in observation group will not receive any anti-cancer therapy. | Other: Observation<br>* Patients in observation group will not receive any anti-cancer therapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | defined as the time from randomization until death from any cause. Patients who withdraw or who are lost to follow-up will be censored at the date last known to be alive. Patients remaining alive throughout the duration of the study will have their survival time censored on the date last seen alive. | two years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence-free Survival | defined as the time from randomization until disease recurrence or death from any cause, whichever happens first. Patients who withdraw or who are lost to follow-up will be censored at the date last known to be alive and recurrence-free. Patients not having an event will be censored at the date last seen alive. | two years | 
| Adverse Events | adverse events during the treatment period using Common Terminology Criteria for Adverse Events (CTCAE) (version 5.0). | two years |