Clinical trial
Pd1 Antibody Sintilimab ± Chemoradiotherapy for Locally Advanced Rectal Cancer
Name
B2019-149
Description
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 4 cycles of neoadjuvant Pd1 antibody Sintilimab,followed by one of the following treatments: (1) surgery and adjuvant treatment, (2)another 4 cycles of sintilimab, followed by radical surgery or observation (only for cCR) . For Cohort B, pMMR/MSS/MSI-L patients will be randomized to receive neoadjuvant chemoradiotherapy ± four cycles of Pd1 antibody Sintilimab,followed by one of the following treatments: (1) curative surgery and four cycles of adjuvant chemotherapy;(2)four cycles of chemotherapy then observation (only cCR after neoadjuvant therapy)
Trial arms
Trial start
2019-10-28
Estimated PCD
2026-10-18
Trial end
2026-10-18
Status
Active (not recruiting)
Phase
Early phase I
Treatment
Oxaliplatin
130mg/m2, d1 q3w, in Capeox regimen (100mg/m2 when used cocurrently with radiotherapy), intravenous infusion
Arms:
Cohort A, Cohort B-arm 1, Cohort B-arm 2
Capecitabine
1000mg/m2, bid, qd1-14, q3w, in Capeox regimen, oral administration
Arms:
Cohort A, Cohort B-arm 1, Cohort B-arm 2
Sintilimab
200mg, d1 q3w, intravenous infusion
Arms:
Cohort A, Cohort B-arm 1
radiotherapy
neoadjuvant radiotherapy with 50Gy to GTV, 45Gy to CTV in 25 fractions.
Arms:
Cohort B-arm 1, Cohort B-arm 2
total mesorectal excision
total mesorectal excision after neoadjuvant treatment
Arms:
Cohort A, Cohort B-arm 1, Cohort B-arm 2
Watch and wait
Watch and wait for cCR patients after neoadjuvant treatment
Arms:
Cohort A, Cohort B-arm 1, Cohort B-arm 2
Size
195
Primary endpoint
complete response rate
6 weeks after curative surgery for pCR; 6 weeks after the completion of neoadjuvant therapy for cCR
Eligibility 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.
Protocol
{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 195, 'type': 'ESTIMATED'}}
Updated at
2023-02-01
1 organization
3 drugs
2 indications
Organization
Sun Yat-sen UniversityDrug
mFOLFOX6Indication
Colorectal Cancer Stage IIIndication
Colorectal Cancer Stage IIIDrug
UTD1Drug
PD-1 antibody