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

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

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.

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.

Inclusion Criteria:

1. Age: 18-70 years;
2. Primary resectable extrahepatic cholangiocarcinoma and gallbladder cancer proved by pathology which underwent radical surgery;
3. Pathology indicates R0 with T2-4 or N1; or R1;
4. ECOG PS 0-1;
5. 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;
6. At least 6 months of life expectancy.

Exclusion Criteria:

1. Pregnant or breastfeeding women, or expecting to conceive or father children within the projected duration of the trial;
2. Received previous anti-cancer therapies;
3. With purulent, infected or delayed healed wounds;
4. Have risky bleeding events requiring transfusion, operation or local therapies, continuous medication in the past 3 months;
5. Have thromboembolism in the past 6 months, including myocardial infarction, unstable angina, stroke or transient ischemic attack, pulmonary embolism, deep vein thrombosis;
6. Have taken aspirin (>325mg/day) or other antiplatelet drugs continuously for 10 days or more within 2 weeks before enrolment;
7. Uncontrollable hypertension, systolic pressure>140mmHg or diastolic pressure>90mmHg after best medical care, or history of hypertensive crisis or hypertensive encephalopathy;
8. Symptomatic congestive heart failure (NYHA class II-IV). Symptomatic or badly-controlled arrhythmia. Congenital long QT syndrome or modified QTc>500ms upon screening;
9. Have active autoimmune diseases that require systemic treatment within 2 years before enrolment;
10. Active tuberculosis, having antituberculosis therapy at present or within 1 year;
11. Have a known history of prior invasive malignancies within 5 years before enrolment;
12. Have other uncontrollable comorbidities;
13. Infection of HIV, known syphilis requiring treatment;
14. Allergic to chemotherapeutics.