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

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.

Study Overview

• Status: Recruiting
• Conditions: Rectal Cancer; Radiotherapy; Anti-PD-1 Antibody; MSI-H; Mmr Deficiency
• Intervention / Treatment: Drug: Sintilimab; Radiation: Hypofractionated Radiotherapy

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.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Xiaofen Li, M.D.; Phone Number: +86-28-85422589; Email: lxf0827@163.com

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Recruiting
      • West China Hospital of Sichuan University
      • Contact: Xiaofen Li, M.D.; Phone Number: +86-28-85422589; Email: lxf0827@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental arm; Sintilimab+Hypofractionated radiotherapy	Drug: Sintilimab; Sintilimab+Hypofractionated radiotherapy; Radiation: Hypofractionated Radiotherapy; Hypofractionated Radiotherapy

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: West China Hospital
• Collaborators: First Affiliated Hospital of Chongqing Medical University; Sichuan Cancer Hospital and Research Institute; Yunnan Cancer Hospital; Chengdu Third People's Hospital; The Affiliated Hospital Of Southwest Medical University
• Investigators: Principal Investigator: Meng Qiu, M.D., West China Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 14, 2020
• Primary Completion (Anticipated): November 1, 2022
• Study Completion (Anticipated): November 1, 2022

Study Registration Dates

• First Submitted: November 11, 2020
• First Submitted That Met QC Criteria: November 14, 2020
• First Posted (Actual): November 19, 2020

Study Record Updates

• Last Update Posted (Actual): April 27, 2022
• Last Update Submitted That Met QC Criteria: April 25, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms
• Other Study ID Numbers: 201919

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No