COmbination of Radiotherapy With Anti-PD-1 Antibody for unREseCtable inTrahepatic Cholangiocarcinoma

Overview

The study is a multicenter phase II randomized trial. The purpose is to investigate both the efficacy and safety of radiotherapy combined with anti-PD-1 antibody and chemotherapy (gemcitabine+cisplatin) in unresectable intrahepatic cholangiocarcinoma patients.

Full Title of Study: “Combination of Radiotherapy With Anti-PD-1 Antibody for Unresectable Intrahepatic Cholangiocarcinoma”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: November 2024

Detailed Description

The trial will recruit 184 patients, and they will be randomized (1:1) into two groups (radiotherapy+anti-PD-1 group, gemcitabine+cisplatin group). Patients in radiotherapy+anti-PD-1 group will receive conventional intensity-modulated radiotherapy or stereotactic body radiation therapy first for a total dose more than 40Gy. Camrelizumab 200mg intravenously every 3 weeks will be initiated within 7 days after radiotherapy. Patients in chemotherapy group will receive cisplatin 25mg/m2 intravenously (day 1 and day 8) and then gemcitabine 1000mg/m2 intravenously (day 1 and day 8) every 3 weeks (1 cycle), for 8 cycles.

Interventions

  • Combination Product: Radiotherapy+anti-PD-1
    • The total radiation dose is over 40Gy without damaging organic fucntion. Conventional intensity-modulated radiotherapy or stereotactic body radiation therapy are both allowed. Camrelizumab 200mg intravenously every 3 weeks will be initiated within 7 days after radiotherapy. Patients will receive camrelizumab until clinical or radiographic disease progression, unacceptable toxicity, death, termination of the study or withdrawal. If disease progression is confirmed by radiologic examinations, another 200mg camrelizumab should be applied to the patient, then another radiologic examination will be performed 4 weeks later to confirm or exclude progression. If progression is confirmed, the camrelizumab should be stopped.
  • Drug: Gemcitabine+cisplatin
    • Cisplatin 25mg/m2 intravenously (day 1 and day 8) and then gemcitabine 1000mg/m2 intravenously (day 1 and day 8) every 3 weeks (1 cycle), for 8 cycles.

Arms, Groups and Cohorts

  • Experimental: Radiotherapy+anti-PD-1
    • The total radiation dose is over 40Gy without damaging organic fucntion. Conventional intensity-modulated radiotherapy or stereotactic body radiation therapy are both allowed. Camrelizumab 200mg intravenously every 3 weeks will be initiated within 7 days after radiotherapy. Patients will receive camrelizumab until clinical or radiographic disease progression, unacceptable toxicity, death, termination of the study or withdrawal. If disease progression is confirmed by radiologic examinations, another 200mg camrelizumab should be applied to the patient, then another radiologic examination will be performed 4 weeks later to confirm or exclude progression. If progression is confirmed, the camrelizumab should be stopped.
  • Active Comparator: Gemcitabine+cisplatin
    • Cisplatin 25mg/m2 intravenously (day 1 and day 8) and then gemcitabine 1000mg/m2 intravenously (day 1 and day 8) every 3 weeks (1 cycle), for 8 cycles.

Clinical Trial Outcome Measures

Primary Measures

  • Progression-free survival, PFS
    • Time Frame: two years
    • defined as the time from randomization until disease progression 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 progression free. Patients not having an event will be censored at the date last seen alive.

Secondary Measures

  • Overall survival, OS
    • Time Frame: two years
    • 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.
  • Adverse events, AE
    • Time Frame: two years
    • adverse events during the treatment period using Common Terminology Criteria for Adverse Events (CTCAE) (version 5.0).
  • Tumor response
    • Time Frame: two years
    • measured according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1 by means of computed tomography (CT) or magnetic resonance imaging (MRI) at each follow-up.

Participating in This Clinical Trial

Inclusion Criteria

1. Age: 18-75 years;

2. Primary unresectable ICC or recurrent unresectable ICC following curative therapies proved by pathology;

3. No previous systemic chemotherapy or immunotherapy;

4. The volume of normal liver is larger than 700ml, eligible for radiotherapy, chemotherapy and immunotherapy after evaluation of specialized experts;

5. At least one measurable lesion based on RECIST 1.1 criteria;

6. Child-Pugh A class;

7. ECOG PS 0-1;

8. Adequate hematologic, hepatic and renal function: ANC ≥ 1.5×10^9/L, Hb ≥ 90g/L, PLT ≥ 100 x10^9/L, albumin ≥ 28g/L, total bilirubin < 1.5×ULN at diagnosis or after biliary drainage, ALT and AST < 5×ULN, BUN、CREA<1.5×ULN, creatinine clearance rate ≥ 45ml/min;

9. At least 12 weeks of life expectancy.

Exclusion Criteria

1. Have acute or chronic active hepatitis B or C, HBV-DNA>2000IU/ml or 104 copy/ml; HCV-RNA>103 copy/ml; both HBsAg and HCV antibody are positive. If the related results become lower than above standards after anti-viral treatment, the patients are qualified for enrolment;

2. Have metastasis in extrahepatic distant organs including lung, central nervous system, bone and etc. Or extrahepatic lymph node metastasis beyond abdomen;

3. Have risky bleeding events requiring transfusion, operation or local therapies, continuous medication in the past 3 months;

4. Have thromboembolism in the past 6 months, including myocardial infarction, unstable angina, stroke or transient ischemic attack, pulmonary embolism, deep vein thrombosis;

5. Have taken aspirin (>325mg/day) or other antiplatelet drugs continuously for 10 days or more within 2 weeks before enrolment;

6. Uncontrollable hypertension, systolic pressure>140mmHg or diastolic pressure>90mmHg after best medical care, or history of hypertensive crisis or hypertensive encephalopathy;

7. Symptomatic congestive heart failure (NYHA class II-IV). Symptomatic or badly-controlled arrhythmia. Congenital long QT syndrome or modified QTc>500ms upon screening;

8. Have active autoimmune diseases that require systemic treatment within 2 years before enrolment;

9. Active tuberculosis, having antituberculosis therapy at present or within 1 year;

10. Have a known history of prior invasive malignancies within 5 years before enrolment;

11. Pregnant or breastfeeding women, or expecting to conceive or father children within the projected duration of the trial;

12. Have other uncontrollable comorbidities;

13. Infection of HIV, known syphilis requiring treatment;

14. Allergic to elements of camrelizumab, gemcitabine or cisplatin.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 75 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Sun Yat-sen University
  • Provider of Information About this Clinical Study
    • Principal Investigator: Ming Kuang, Professor – Sun Yat-sen University
  • Overall Official(s)
    • Ming Kuang, PhD, Study Chair, First Affiliated Hospital, Sun Yat-Sen University
  • Overall Contact(s)
    • Ming Kuang, PhD, 008687755766, kuangm@mail.sysu.edu.cn

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