Pd1 Antibody Sintilimab ± Chemoradiotherapy for Locally Advanced Rectal Cancer

• Status: Recruiting
• Trial end date: 2026-10-18
• Target enrollment: 0
• Participant gender: All

Summary

In this study, participants with locally advanced rectal cancer patients will be treated according to MMR/MSI status. There will be two cohorts in this study: Cohort A and Cohort B. For Cohort A, dMMR or MSI-H patients will receive neoadjuvant Pd1 antibody Sintilimab and surgery or watch and wait, followed by adjuvant treatment. For Cohort B, pMMR/MSS/MSI-L patients will be randomized to receive neoadjuvant chemoradiotherapy ± Pd1 antibody Sintilimab， followed by surgery or watch and wait, and adjuvant treatment.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sun Yat-sen University
• Treatments: Antibodies; Capecitabine; Immunoglobulins; Oxaliplatin

Criteria

Inclusion Criteria:

1. Histologically proven colorectal adenocarcinoma;

2. Cohort 1: Biopsy tissues with IHC indicates deficient mismatch repair(dMMR),that is,the loss of at least one of the four proteins ,MSH1,MSH2,MSH6,PMS2;or gene detection implies MSI-H; Cohort 2: Biopsy tissues with IHC indicates proficient mismatch repair(pMMR),that is positivity of all four proteins ,MSH1,MSH2,MSH6,PMS2;or gene detection implies MSS/MSI-L

3. Clinical stage for rectal cancer patients is cT3-4N0M0 or cTxN+M0;

4. Preoperative staging methods: all patients need to accept digital rectal examination(DRE).Patients with rectal cancer undergo high-resolution MRI±ultrasound colonoscopy/transrectal ultrasound for preoperative staging. Perienteric lymph nodes with short diameter ≥10mm or the shape of lymph nodes and its MRI characteristics are consistent with typical lymph node metastasis. If endoscopic ultrasonography is used in combination, and there is a contradiction between staging methods, the data should be submitted to the evaluation team of our center for the accurate staging;

5. No symptoms of ileus; or ileus is alleviated after proximal colostomy.

6. No rectal surgery except preventative stoma;

7. No chemotherapy or radiotherapy;

8. No biotherapy (e.g.monoclonal antibodies), immunotherapy (e.g.anti-PD-1 antibody,anti-PD-L1 antibody,anti-PD-L2 antibody or CTLA-4 antibody),or other clinical trials agents;

9. No limit to previous endocrine therapy.

10. Age between 18 and 75 years;

11. ECOG performance status of 0 or 1;

12. Life expectancy: more than 2 years;

13. Hematopoietic: WBC>3×109/L;PLT>80×109/L; Hb>90g/L;

14. Hepatic: ALT and AST<2 times upper limit of normal (ULN); bilirubin<1.5 times ULN;

15. Renal: creatinine <1.5 times ULN or creatinine clearance ≥ 60 mL/min.

Exclusion Criteria:

1. Arrhythmias require antiarrhythmic therapy (with the exception of β-blockers or digoxin), symptomatic coronary artery disease or local myocardial ischemia (myocardial infarction within the past 6 months) or congestive heart failure exceeding NYHA II;

2. Severe hypertension with poor control after medication;

3. A known history of testing positive for HIV or chronic hepatitis B or C (high copy virus DNA) at active stage;

4. Patients with active tuberculosis (TB) are receiving anti-tuberculosis treatment or have received anti-tuberculosis treatment within 1 year before screening;

5. Other active severe clinical infections (NCI-CTC5.0);

6. Apparent distant metastasis away from the pelvic before surgery;

7. Cachexia, organ function decompensation;

8. Previous pelvic or abdominal radiotherapy;

9. Multiple primary colorectal cancers;

10. Epilepsy require medical treatment (such as steroid or antiepileptic therapy);

11. Other malignancy within the past 5 years with the exception of effectively treated carcinoma in situ of the cervix or basal cell carcinoma of the skin;

12. Drug abuse and medical, psychological or social factors that may interfere with patients' participation in the study or affect the evaluation of the study;

13. Patients have any active autoimmune diseases or a history of autoimmune diseases(including but not limited to: interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, nephritis, hyperthyroidism and decreased thyroid function; patients with vitiligo or with complete remission of asthma in childhood and without any intervention in adulthood may be included; patients with asthma requiring bronchodilators intervention are not included.

14. Received any anti-infection vaccine (e.g. influenza vaccine, chickenpox vaccine, etc.) within 4 weeks before enrollment;

15. Complications require long-term treatment with immunosuppressive drugs, or requiring systemic or local use of immunosuppressive corticosteroids(>10mg/day prednisone or other therapeutic hormones);

16. Known or suspected allergy to the study drugs or to any drugs related to this trial;

17. Any unstable condition or which endangers the patients' safety and compliance;

18. Pregnant or breast-feeding women who are fertile without effective contraception;

19. Refuse to sign the informed consent.