A Single-arm, Multicenter, Phase II Clinical Study of Chemoradiotherapy Followed by Tislelizumab Combined With Chemotherapy for Organ Preservation in Resectable Low Rectal Cancer：the RELIEVE-01 Study
Overview
- Phase
- Phase 2
- Intervention
- Radiotherapy
- Conditions
- RECTAL NEOPLASMS
- Sponsor
- Fudan University
- Enrollment
- 46
- Primary Endpoint
- Complete Response rate (CR rate)
- Status
- Not yet recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
This is an open-label, multi-center, single-arm clinical study. All patients received concurrent chemoradiation therapy (CRT) followed by 4 cycles of tislelizumab combined with CAPOX, then underwent clinical response assessment. Patients who achieved CR (cCR+ pCR confirmed by local resection of ncCR) continue tislelizumab combined with CAPOX for another 4 cycles and tislelizumab for 9 cycles, then Watch and Wait. Patients who did not achieved CR underwent total mesorectal excision (TME).
Investigators
Xu jianmin
Chief Physician
Shanghai Zhongshan Hospital
Eligibility Criteria
Inclusion Criteria
- •Able to provide written informed consent, understand and comply with the requirements and evaluation schedule
- •≥18, ≤75 years old
- •Histologically confirmed rectal adenocarcinoma
- •immunohistochemistry confirmed pMMR (positive for MLH1, MSH2, MSH6 and PMS2), or PCR /NGS confirmed MSI-L or MSS
- •The distance from the lower edge of the tumor to the anal verge is ≤5 cm through colonoscopy, digital anal examination or MRI
- •clinical stage cT1-3N1M0 or cT2-3N0M0 (the 8th UICC/AJCC; T and N is evaluated by MRI)
- •Resectable primary tumor assessed by the Investigator
- •Have not received any anti-tumor treatment for rectal cancer
- •ECOG PS ≤ 1
- •Adequate organ function
Exclusion Criteria
- •Histologically confirmed poorly differentiated/undifferentiated adenocarcinoma, mucinous adenocarcinoma and signet ring cell carcinoma
- •Have received any treatments for rectal cancer, or evidence of distant metastasis
- •Presence of following high risk factors assessed by MRI: MRF +, EMVI+, cN2, Positive lateral lymph nodes, T3d
- •Presence or in high risk of obstruction, perforation or bleeding;
- •Not suitable for long-course radiotherapy
- •Cannot tolerate surgery
- •≥2 colorectal cancer lesions at the same time
- •Contraindications for MRI examination
- •Other malignant tumors in the past or at the same time
- •Have an active autoimmune disease requiring systemic therapy within the past 2 years
Arms & Interventions
tislelizumab
CRT followed by 4 cycles of tislelizumab plus CAPOX and clinical response assessment: participants with CR (cCR+ pCR confirmed by local resection of ncCR): another 4 cycles of tislelizumab plus CAPOX and 9 cycles of tislelizumab, then watch and wait. participants with non-CR: underwent TME
Intervention: Radiotherapy
tislelizumab
CRT followed by 4 cycles of tislelizumab plus CAPOX and clinical response assessment: participants with CR (cCR+ pCR confirmed by local resection of ncCR): another 4 cycles of tislelizumab plus CAPOX and 9 cycles of tislelizumab, then watch and wait. participants with non-CR: underwent TME
Intervention: Tislelizumab
tislelizumab
CRT followed by 4 cycles of tislelizumab plus CAPOX and clinical response assessment: participants with CR (cCR+ pCR confirmed by local resection of ncCR): another 4 cycles of tislelizumab plus CAPOX and 9 cycles of tislelizumab, then watch and wait. participants with non-CR: underwent TME
Intervention: Capecitabine
tislelizumab
CRT followed by 4 cycles of tislelizumab plus CAPOX and clinical response assessment: participants with CR (cCR+ pCR confirmed by local resection of ncCR): another 4 cycles of tislelizumab plus CAPOX and 9 cycles of tislelizumab, then watch and wait. participants with non-CR: underwent TME
Intervention: Oxaliplatin
Outcomes
Primary Outcomes
Complete Response rate (CR rate)
Time Frame: From first dose up to 12 months, approximately
defined as the proportion of participants with clinical complete response(cCR) or near clinical complete response (ncCR) who achieved local resection confirmed pCR determined by the investigators after CRT and 4 cycles of CAPOX plus tislelizumab.
Secondary Outcomes
- 1/2/3 year EFS rate(From first dose of radiotherapy up to 36 months, approximately)
- 1/2/3 year organ-preservation rate(From first dose of radiotherapy up to 36 months, approximately)
- 1/2/3 year OS rate(From first dose of radiotherapy up to 36 months, approximately)
- Percentage of Participants With Adverse Events(From first dose of radiotherapy up to 36 months, approximately)