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

Rectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04636008
• Other study ID #: 201919
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: August 14, 2020
• Est. completion date: November 2022

Study information

• Verified date: April 2022
• Source: West China Hospital
• Contact: Xiaofen Li, M.D.
• Phone: +86-28-85422589
• Email: lxf0827[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: November 2022
• Est. primary completion date: November 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Sintilimab
Sintilimab+Hypofractionated radiotherapy

Radiation:
• Hypofractionated Radiotherapy
Hypofractionated Radiotherapy

Locations

Country	Name	City	State
China	West China Hospital of Sichuan University	Chengdu	Sichuan

Sponsors (6)

Lead Sponsor	Collaborator
West China Hospital	Chengdu Third People's Hospital, First Affiliated Hospital of Chongqing Medical University, Sichuan Cancer Hospital and Research Institute, The Affiliated Hospital Of Southwest Medical University, Yunnan Cancer Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse reaction	Adverse reaction after receiving treatment of Sintilimab combined with hypofractionated radiotherapy and perioperative complications	up to 10 weeks
Secondary	Pathological response rate	Pathological response rate after treatment	6-8 weeks after radiotherapy
Secondary	Complete resection rate	Complete resection rate after treatment	6-8 weeks after radiotherapy
Secondary	Quality of life questionnaire	Quality of life during treatment	up to 10 weeks