Sintilimab Plus Hypofractionated Radiotherapy for MSI-H/dMMR Rectal Cancer

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Anti-PD-1 Antibody, Radiotherapy, Rectal Cancer, MSI-H, Mmr Deficiency

Intervention / Treatment
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* Drug: Sintilimab
* Radiation: Hypofractionated Radiotherapy


Participation Criteria
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Eligibility Criteria
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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; Other conditions that investigators consider not suitable for this study.

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental arm<br>Sintilimab+Hypofractionated radiotherapy | Drug: Sintilimab<br>* Sintilimab+Hypofractionated radiotherapy<br>Radiation: Hypofractionated Radiotherapy<br>* Hypofractionated Radiotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse reaction | Adverse reaction after receiving treatment of Sintilimab combined with hypofractionated radiotherapy and perioperative complications | up to 10 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological response rate | Pathological response rate after treatment | 6-8 weeks after radiotherapy | 
| Complete resection rate | Complete resection rate after treatment | 6-8 weeks after radiotherapy | 
| Quality of life questionnaire | Quality of life during treatment | up to 10 weeks |