RecruitingPhase 1Phase 2NCT04636008

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

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

Sponsor

West China Hospital

Enrollment

20 participants

Start Date

Aug 14, 2020

Study Type

INTERVENTIONAL

Conditions

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

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.

Eligibility

Min Age: 18 Years

Inclusion Criteria10

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 Criteria11

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.