Combining Sintilimab with targeted radiotherapy for specific 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 study is testing if combining a new cancer drug called Sintilimab with a special type of radiation therapy can help people with certain types of rectal cancer do better before surgery.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: West China Hospital (Academic / other)
• Drugs / interventions: Sintilimab
• Locations: 1 site (Chengdu, Sichuan)
• Trial ID: NCT04636008 on ClinicalTrials.gov

What this trial studies

This interventional study aims to evaluate the safety and effectiveness of Sintilimab, an anti-PD-1 antibody, in conjunction with hypofractionated radiotherapy for patients with microsatellite instability-high (MSI-H) or DNA mismatch repair-deficient (dMMR) non-metastatic rectal cancer. Participants will receive a specific radiotherapy regimen and Sintilimab before undergoing radical surgery. The study is designed to assess how well this combination treatment works compared to traditional approaches.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with histologically confirmed MSI-H/dMMR rectal adenocarcinoma who have not received prior treatment for their cancer.

Not a fit: Patients with distant metastasis or those who have previously undergone treatment for rectal cancer may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with MSI-H/dMMR rectal cancer, potentially improving their outcomes.

How similar studies have performed: Other studies have shown promising results with similar immunotherapy and radiotherapy combinations, indicating potential for success in this approach.

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.

Where this trial is running

Chengdu, Sichuan

• West China Hospital of Sichuan University — Chengdu, Sichuan, China (Recruiting)

Study contacts

• Principal investigator: Meng Qiu, M.D. — West China Hospital
• Study coordinator: Meng Qiu, M.D.

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