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
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 46
- 主要终点
- Complete Response rate (CR rate)
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •Female subjects with the ability to become pregnant must have a serum pregnancy test with a negative result within 72 hours before the first dose, and be willing to use highly effective contraceptive methods during the trial and 120 days after the last dose. Male subjects whose partners are women of childbearing potential should be surgically sterilized or agree to use a highly effective method of contraception during the trial and for 120 days after the last dose.
排除标准
- •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
- •HIV infection
- •Untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers (HBV DNA > 500 IU/mL) or active HCV carriers with detectable HCV RNA;
- •Hypersensitivity to any ingredient of tislelizumab, capecitabine, and oxaliplatin or to any component of the container
- •Other conditions judged by the researcher that do not meet the enrollment requirements
研究组 & 干预措施
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
干预措施: Radiotherapy (Radiation)
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
干预措施: Tislelizumab (Drug)
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
干预措施: Capecitabine (Drug)
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
干预措施: Oxaliplatin (Drug)
结局指标
主要结局
Complete Response rate (CR rate)
时间窗: 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.
次要结局
- 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)
研究者
Xu jianmin
Chief Physician
Shanghai Zhongshan Hospital