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

NCT04636008 | Recruiting Phase 1

• 1 other identifier: 201919
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Adverse reaction

  Adverse reaction after receiving treatment of Sintilimab combined with hypofractionated radiotherapy and perioperative complications

  up to 10 weeks

Secondary Outcomes (3)

• Pathological response rate

  6-8 weeks after radiotherapy

• Complete resection rate

  6-8 weeks after radiotherapy

• Quality of life questionnaire

  up to 10 weeks

Study Arms (1)

Experimental arm

EXPERIMENTAL

Sintilimab+Hypofractionated radiotherapy

Drug: Sintilimab; Radiation: Hypofractionated Radiotherapy

Interventions

Sintilimab DRUG

Sintilimab+Hypofractionated radiotherapy

Experimental arm

Hypofractionated Radiotherapy RADIATION

Hypofractionated Radiotherapy

Experimental arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• Informed consent form signed;
• Life expectancy of ≥3 months.

You may not qualify if:

• 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;
• 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.

Sponsors & Collaborators

• West China Hospital: lead
• First Affiliated Hospital of Chongqing Medical University: collaborator
• Yunnan Cancer Hospital: collaborator
• Sichuan Cancer Hospital and Research Institute: collaborator
• Chengdu Third People's Hospital: collaborator
• The Affiliated Hospital Of Southwest Medical University: collaborator

Study Sites (1)

West China Hospital of Sichuan University

Chengdu, Sichuan, 610041, China

RECRUITING

Related Publications (1)

• Li X, Fang C, Wang X, Yu Y, Wang Z, Qiu M. Neoadjuvant treatment of sintilimab plus hypofractionated radiotherapy for MSI-H/dMMR rectal cancer: A prospective, multicenter, phase Ib study. Cancer Med. 2022 Dec;11(23):4405-4410. doi: 10.1002/cam4.4720. Epub 2022 Mar 29.

  PMID: 35352512 DERIVED

MeSH Terms

Conditions

Rectal Neoplasms; Turcot syndrome

Interventions

sintilimab; Radiation Dose Hypofractionation

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Dose Fractionation, Radiation; Radiotherapy Dosage; Radiotherapy; Therapeutics

Study Officials

• Meng Qiu, M.D.

  West China Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Meng Qiu, M.D.

CONTACT

+86-28-85422589; hxqmtg@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: November 11, 2020
• First Posted: November 19, 2020
• Study Start: August 14, 2020
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: August 6, 2024

Record last verified: 2024-08

Locations

CN (1)