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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Biliary Tract Cancer; Gallbladder Cancer; Extrahepatic Cholangiocarcinoma
• Intervention / Treatment: Drug: Chemotherapy; Procedure: Immunotherapy; Radiation: Radiotherapy; Other: Observation

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 92
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • The First Affiliated Hospital of Sun Yat-sen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; 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; Capecitabine (1,330 mg/m2 per day, in divided doses twice daily, 7 days per week).; Procedure: Immunotherapy; Camrelizumab 200mg intravenously every 3 weeks until clinical or radiographic disease progression, unacceptable toxicity, death, termination of the study or withdrawal.; Radiation: Radiotherapy; 45 Gy to regional lymph nodes and 54 to 59.4 Gy to preoperative tumor bed.
Placebo Comparator: Observation; Patients in observation group will not receive any anti-cancer therapy.	Other: Observation; Patients in observation group will not receive any anti-cancer therapy.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Study Chair: Ming Kuang, PhD, First Affiliated Hospital, Sun Yat-Sen University

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2020
• Primary Completion (Anticipated): June 1, 2024
• Study Completion (Anticipated): June 1, 2024

Study Registration Dates

• First Submitted: April 2, 2020
• First Submitted That Met QC Criteria: April 2, 2020
• First Posted (Actual): April 3, 2020

Study Record Updates

• Last Update Posted (Actual): June 23, 2020
• Last Update Submitted That Met QC Criteria: June 20, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Gallbladder Diseases; Biliary Tract Diseases; Cholangiocarcinoma; Biliary Tract Neoplasms; Gallbladder Neoplasms
• Other Study ID Numbers: BTC001

Drug and device information, study documents

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