The Safety and Efficacy of Sintilimab Combined With Hypofractionated Radiotherapy in MSI-H/dMMR Rectal Cancer: a Prospective, Single-arm, Multicenter, Phase Ib Study

West China Hospital1 site in 1 country20 target enrollmentAugust 14, 2020

ConditionsAnti-PD-1 Antibody Radiotherapy Rectal Cancer MSI-H Mmr Deficiency

InterventionsSintilimab Hypofractionated Radiotherapy

Overview

Phase: Phase 1
Intervention: Sintilimab
Conditions: Anti-PD-1 Antibody
Sponsor: West China Hospital
Enrollment: 20
Locations: 1
Primary Endpoint: Adverse reaction
Status: Recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This prospective, single-arm study is conducted to investigate the safety and efficacy of Sintilimab combined with hypofractionated radiotherapy in patients with microsatellite instability-high (MSI-H)/ DNA mismatch repair-deficient (dMMR) non-metastatic rectal cancer.

Detailed Description

The patients meet the inclusion criteria. After signing the informed consent, they are given radiotherapy 5Gyx5 and sintilimab 200mg ivgtt D1, D15, D29. Radical surgery is performed 6-8 weeks after radiotherapy.

Registry

clinicaltrials.gov

Start Date

August 14, 2020

End Date

December 2024

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

West China Hospital

Responsible Party

Principal Investigator

Meng Qiu

Prof.

West China Hospital

Eligibility Criteria

Inclusion Criteria

•Histologically confirmed rectal adenocarcinoma;
•With DNA mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) status, whether or not being Lynch syndrome;
•Not received any anti-rectal cancer treatment previously; for patients with Lynch syndrome, not received any anti-tumor therapy about rectal cancer diagnosed this time;
•No distant metastasis except for lateral lymph nodes on thoracic and abdominal enhanced computed tomography (CT) scans; the distance between tumor's lower edge and anus within 15cm; clinical T stage ≥T2 on high-resolution pelvic magnetic resonance imaging (MRI)；
•Men and women ≥18 years of age;
•Eastern Cooperative Oncology Group performance status score 0 or 1;
•Adequate hematologic, hepatic, renal, thyroid and cardiac function: hemoglobin ≥90 g/L, neutrophils ≥1500/mm3, platelets ≥75,000/mm3; aspartate aminotransferase and alanine aminotransferase ≤3.0 × upper limit of normal (ULN), bilirubin ≤1.5 × ULN; creatinine ≤1.5 × ULN, creatinine clearance ≥50 mL/min; activated partial thromboplastin time, prothrombin time and international normalized ratio ≤1.5 × ULN; serum albumin ≥28 g/L；thyroid stimulating hormone and free thyroxine within ±10% of normal levels; no obvious abnormality in electrocardiogram;
•Not received blood, blood products and hematopoietic growth factor (e.g. granulocyte colony-stimulating factor) within 2 weeks before inclusion;
•Informed consent form signed;
•Life expectancy of ≥3 months.

Exclusion Criteria

•Allergic disease history, severe hypersensitivity to drugs, antibody products or Sintilimab;
•Other malignancy history with disease free survival \<5 years, except for curative in situ cervical cancer, curative skin basal cell carcinoma and curative gastrointestinal cancer by endoscopic mucoresection;
•Current or past history of autoimmune diseases, including but not limited to: interstitial lung disease, uveitis, enteritis，active hepatitis (HBV DNA≥103 copies/mL after regular antiviral therapy)，nephritis, hyperthyroidism and hypothyroidism;
•Immunosuppressant or corticosteroid (systemic or local) use to suppress immune function within 2 weeks before inclusion;
•Severe infection needing intravenous antibiotics, antifungal agents or antiviral drugs, et al;
•Congenital or acquired immunodeficiency such as HIV infection; active Hepatitis B (HBV DNA≥103 copies/mL after regular antiviral therapy);
•Having one of the following complications: massive gastrointestinal hemorrhage, gastrointestinal perforation or obstruction; symptomatic heart diseases including unstable angina, myocardial infarction and heart failure; uncontrollable diabetes mellitus or hypertension; uncontrollable diarrhea (interfering with daily activities although receiving adequate treatment);
•Bleeding tendency or receiving thrombolytic or anticoagulant therapy;
•Pregnant or breastfeeding female; male and female unwilling to take any contraceptive measures;
•Psychiatric disorders that would interfere with cooperation with the requirements of the study;