Node-sparing Radiotherapy Combined with Total Neoadjuvant CAPOX and Sintilimab for MSS Middle and Low Rectal Cancer
- Conditions
- Locally Advanced Rectal Cancer
- Interventions
- Radiation: node-sparing short-course radiotherapyProcedure: TME surgeryProcedure: watch and wait
- Registration Number
- NCT06204094
- Lead Sponsor
- Jinhua Central Hospital
- Brief Summary
phase II clinical trial to evaluate node-sparing short-course radiation combined with total neoadjuvant CAPOX and Sintilimab for MSS locally advanced rectal cancers.
- Detailed Description
This is an open-label, prospective, single-center phase II clinical trial to evaluate node-sparing short-course radiation (Radiation targeting the tumor bed without irradiating surrounding tumor-draining lymph nodes) combined with total neoadjuvant CAPOX and PD-1 Inhibitor (Sintilimab) for patients with MSS locally advanced of middle and low rectal cancer. A total of 47 patients will be enrolled in this trial. The primary endpoint is the complete response(CR) rate, which includes cCR and pCR. The organ preservation rate, tumor regression grade, 3-year DFS, 3-year OS, and adverse effects will also be analyzed.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 37
- Patients who have a strong willingness to preserve the anus and are willing to receive neoadjuvant therapy.
- Male or Female aged 18-75.
- Patients diagnosed with low rectal cancer within 10 cm from the lower edge of the tumor to the anal verge by pelvic MRI and anorectoscopy, the clinical stage is cT2N+M0/cT3-4aN0/+M0, the lymph nodes are limited to the mesorectum, the circumferential resection margin is negative.
- Histologically confirmed rectal adenocarcinoma; Genetic testing suggests MSI-L or MSS, or tumor biopsy immunohistochemistry reveals pMMR, that is, MSH1, MSH2, MSH6, and PMS2 are all positive.
- Eastern Cooperative Oncology Group (ECOG) 0-1.
- No previous treatment(including anti-tumor therapy、immunotherapy or pelvic radiation).
- Adequate hematologic, hepatic, renal, thyroid and cardiac function: white blood cells ≥3500/mm3, neutrophils ≥1800/mm3, platelets ≥100,000/mm3, hemoglobin ≥100 g/L; activated partial thromboplastin time, prothrombin time and international normalized ratio ≤1.5 × ULN; aspartate aminotransferase and alanine aminotransferase ≤3.0 × upper limit of normal (ULN), bilirubin ≤1.25 × ULN, serum albumin ≥28 g/L. creatinine clearance ≥50 mL/mi, creatinine ≤1.5 × ULN;
- Informed consent form signed.
- Patients with a previous history of malignant tumors besides rectal cancer.
- Patients with distant metastases before enrollment.
- Patients with positive internal or external iliac lymph nodes are assessed by MRI or CT.
- Patients with obstruction, perforation, or bleeding that require emergency surgery.
- Patients with severe concomitant diseases and estimated survival time ≤ 5 years.
- Allergic to any component of the therapy.
- Patients with poorly differentiated adenocarcinoma, signet ring cell carcinoma, or mucinous adenocarcinoma.
- Patients who received immunosuppressive or systemic hormone therapy for immunosuppressive purposes within 1 month prior to the initiation of therapy.
- Patients who have received any other experimental drug (including immunotherapy) or participated in another interventional clinical trial within 30 days before screening.
- Factors leading to study termination, such as alcoholism, drug abuse, other serious illnesses (including psychiatric disorders) requiring combination therapy, and patients with severe laboratory abnormalities.
- Patients with congenital or acquired immune deficiency (such as HIV infection).
- Vulnerable groups, including mentally ill, cognitively impaired, critically ill patients, minors, pregnant or lactating women, illiterate, etc.
Other conditions that investigators consider not suitable for this study.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment Arm node-sparing short-course radiotherapy Participants will receive 5\*5Gy node-sparing short-course radiation (radiation targeting the tumor bed without irradiating surrounding tumor-draining lymph nodes) concurrently with total neoadjuvant CAPOX and sintilimab regimens: Oxaliplatin, 130mg/m2, intravenous infusion,d1 of each cycle; Capecitabine, 1000mg/m2, PO, BID, d1-14 and sintilimab, 200mg intravenous infusion d1 of each cycle. CAPOX and sintilimab are repeated every 3 weeks for 8 cycles. Patients with cCR will be managed with a WW strategy, and patients who did not achieve cCR will receive TME surgery. Interventions: * Radiation: node-sparing short-course radiation * Drug: PD-1 antibody (Sintilimab) * Drug: Capecitabine * Drug: Oxaliplatin Treatment Arm TME surgery Participants will receive 5\*5Gy node-sparing short-course radiation (radiation targeting the tumor bed without irradiating surrounding tumor-draining lymph nodes) concurrently with total neoadjuvant CAPOX and sintilimab regimens: Oxaliplatin, 130mg/m2, intravenous infusion,d1 of each cycle; Capecitabine, 1000mg/m2, PO, BID, d1-14 and sintilimab, 200mg intravenous infusion d1 of each cycle. CAPOX and sintilimab are repeated every 3 weeks for 8 cycles. Patients with cCR will be managed with a WW strategy, and patients who did not achieve cCR will receive TME surgery. Interventions: * Radiation: node-sparing short-course radiation * Drug: PD-1 antibody (Sintilimab) * Drug: Capecitabine * Drug: Oxaliplatin Treatment Arm watch and wait Participants will receive 5\*5Gy node-sparing short-course radiation (radiation targeting the tumor bed without irradiating surrounding tumor-draining lymph nodes) concurrently with total neoadjuvant CAPOX and sintilimab regimens: Oxaliplatin, 130mg/m2, intravenous infusion,d1 of each cycle; Capecitabine, 1000mg/m2, PO, BID, d1-14 and sintilimab, 200mg intravenous infusion d1 of each cycle. CAPOX and sintilimab are repeated every 3 weeks for 8 cycles. Patients with cCR will be managed with a WW strategy, and patients who did not achieve cCR will receive TME surgery. Interventions: * Radiation: node-sparing short-course radiation * Drug: PD-1 antibody (Sintilimab) * Drug: Capecitabine * Drug: Oxaliplatin Treatment Arm Sintilimab Participants will receive 5\*5Gy node-sparing short-course radiation (radiation targeting the tumor bed without irradiating surrounding tumor-draining lymph nodes) concurrently with total neoadjuvant CAPOX and sintilimab regimens: Oxaliplatin, 130mg/m2, intravenous infusion,d1 of each cycle; Capecitabine, 1000mg/m2, PO, BID, d1-14 and sintilimab, 200mg intravenous infusion d1 of each cycle. CAPOX and sintilimab are repeated every 3 weeks for 8 cycles. Patients with cCR will be managed with a WW strategy, and patients who did not achieve cCR will receive TME surgery. Interventions: * Radiation: node-sparing short-course radiation * Drug: PD-1 antibody (Sintilimab) * Drug: Capecitabine * Drug: Oxaliplatin Treatment Arm Capecitabine Participants will receive 5\*5Gy node-sparing short-course radiation (radiation targeting the tumor bed without irradiating surrounding tumor-draining lymph nodes) concurrently with total neoadjuvant CAPOX and sintilimab regimens: Oxaliplatin, 130mg/m2, intravenous infusion,d1 of each cycle; Capecitabine, 1000mg/m2, PO, BID, d1-14 and sintilimab, 200mg intravenous infusion d1 of each cycle. CAPOX and sintilimab are repeated every 3 weeks for 8 cycles. Patients with cCR will be managed with a WW strategy, and patients who did not achieve cCR will receive TME surgery. Interventions: * Radiation: node-sparing short-course radiation * Drug: PD-1 antibody (Sintilimab) * Drug: Capecitabine * Drug: Oxaliplatin Treatment Arm Oxaliplatin Participants will receive 5\*5Gy node-sparing short-course radiation (radiation targeting the tumor bed without irradiating surrounding tumor-draining lymph nodes) concurrently with total neoadjuvant CAPOX and sintilimab regimens: Oxaliplatin, 130mg/m2, intravenous infusion,d1 of each cycle; Capecitabine, 1000mg/m2, PO, BID, d1-14 and sintilimab, 200mg intravenous infusion d1 of each cycle. CAPOX and sintilimab are repeated every 3 weeks for 8 cycles. Patients with cCR will be managed with a WW strategy, and patients who did not achieve cCR will receive TME surgery. Interventions: * Radiation: node-sparing short-course radiation * Drug: PD-1 antibody (Sintilimab) * Drug: Capecitabine * Drug: Oxaliplatin
- Primary Outcome Measures
Name Time Method Complete response within 10 days after TNT therapy or surgery Pathological complete response (pCR) ：absence of residual tumour on resected specimen. Clinical complete response（cCR）: no residual tumour visible on imaging or colonoscopy and biopsy.
- Secondary Outcome Measures
Name Time Method Overall survival(OS) 3 years after enrollment the time from randomization to death
Rectal specific quality of life assessment via QLQ-CR29 Baseline and months 3, 6, 12, 24, 36, 60 after the TNT treatment or surgery Rectal specific quality of life according to European Organization for Research and Treatment of Cancer ( EORTC) Quality of life questionnaire QLQ-CR29. scale from 0 to 100, A higher scale represents better function and a higher quality of life.
Tumor regression grade within 10 days after surgery TRG is evaluated according to the AJCC system. TRG0-1 is defined as good response, TRG2 as moderate response, and TRG3 as poor response.
Local recurrence rate(LRR) 3 years after sugery Presence of adenocarcinoma within the rectal wall or within the mesorectum confirmed by pathology.
Disease free survival(DFS) 3 years after treatment the time from randomization to recurrence of tumor or death
Adverse effects rate From date of initiation of treatment until the date of death from any cause, assessed up to 5 years Rate of radiotherapy, chemotherapy and immunotherapy related adverse events
Quality of life assessment via QLQ-C30 Baseline and months 3, 6, 12, 24, 36, 60 after the TNT treatment or surgery Quality of life according to EORTC Quality of life Questionnaire QLQ-C30 version 3.0. Score range from 0 to 100 points. A higher score represents better function and a higher quality of life.
Validation of the Wexner score Months 3, 6, 12, 24, 36, 60 after the TNT treatment or surgery The change of severity of fecal incontinence assessment according to Wexner score. a score from 0-20, where 0 is perfect continence and 20 is complete incontinence.
Trial Locations
- Locations (1)
Zhejiang University Affiliated Jinhua Hospital
🇨🇳Jinhua, Zhejiang, China