Clinical trial NCT04636008: Sintilimab Plus Hypofractionated Radiotherapy for MSI-H/dMMR Rectal Cancer
Official title: The Safety and Efficacy of Sintilimab Combined With Hypofractionated Radiotherapy in MSI-H/dMMR Rectal Cancer: a Prospective, Single-arm, Multicenter, Phase Ib Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Anti-PD-1 Antibody
Radiotherapy
Rectal Cancer
MSI-H
Mmr Deficiency
Lead sponsor: West China Hospital
Sponsor class: OTHER
Collaborators: name: First Affiliated Hospital of Chongqing Medical University
name: Yunnan Cancer Hospital
name: Sichuan Cancer Hospital and Research Institute
name: Chengdu Third People's Hospital
name: The Affiliated Hospital Of Southwest Medical University
First posted: 2020-11-19
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Histologically confirmed rectal adenocarcinoma;
2. With DNA mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) status, whether or not being Lynch syndrome;
3. 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;
4. 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)；
5. Men and women ≥18 years of age;
6. Eastern Cooperative Oncology Group performance status score 0 or 1;
7. 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;
8. Not received blood, blood products and hematopoietic growth factor (e.g. granulocyte colony-stimulating factor) within 2 weeks before inclusion;
9. Informed consent form signed;
10. Life expectancy of ≥3 months.

Exclusion Criteria:

1. Allergic disease history, severe hypersensitivity to drugs, antibody products or Sintilimab;
2. 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;
3. 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;
4. Immunosuppressant or corticosteroid (systemic or local) use to suppress immune function within 2 weeks before inclusion;
5. Severe infection needing intravenous antibiotics, antifungal agents or antiviral drugs, et al;
6. Congenital or acquired immunodeficiency such as HIV infection; active Hepatitis B (HBV DNA≥103 copies/mL after regular antiviral therapy);
7. 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);
8. Bleeding tendency or receiving thrombolytic or anticoagulant therapy;
9. Pregnant or breastfeeding female; male and female unwilling to take any contraceptive measures;
10. Psychiatric disorders that would interfere with cooperation with the requirements of the study;
11. Other conditions that investigators consider not suitable for this study.

Primary outcomes:
measure: Adverse reaction
timeFrame: up to 10 weeks
Secondary outcomes:
measure: Pathological response rate
timeFrame: 6-8 weeks after radiotherapy
measure: Complete resection rate
timeFrame: 6-8 weeks after radiotherapy
measure: Quality of life questionnaire
timeFrame: up to 10 weeks
Other outcomes:
Locations:
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
Study officials:
affiliation: West China Hospital
name: Meng Qiu, M.D.
role: PRINCIPAL_INVESTIGATOR
References: