Neoadjuvant Treatment of Locally Advanced MSS Rectal Cancer With Tislelizumab Combined With CAPOX Regimen: a Prospective, Single-arm, Single-center, Exploratory Phase II Clinical Study
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Pathological complete response (pCR) rate
研究概览
简要总结
This study aims to elucidate the effects of neoadjuvant Tislelizumab combined with chemotherapy in locally advanced MSS rectal cancer.
详细描述
The standard treatment for locally advanced rectal cancer is neoadjuvant chemoradiotherapy followed by total mesorectal excision (TME). Pelvic chemoradiotherapy for locally advanced rectal cancer reduces the risk of disease recurrence in the pelvis to less than 10% and has been standard care in North America since 1990.However, it is associated with short-term and long-term toxic effects that can adversely affect quality of life and physical function.
Immunogenic cell death will be enhanced by oxaliplatin-induced immunogenicity and combined with anti-programmed cell death 1 (PD-1) monoclonal antibodies for neoadjuvant therapy. The study will conduct 2 or 4 cycles of Tislelizumab with Oxaliplatin and Capecitabine, followed by TME surgery. This study's primary endpoint is the proportion of pCR in the pathological specimens of surgically resected tumors.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years old and ≤70 years old.
- •Pathologically diagnosed MSS ((confirmed by microsatellite stable detection or next-generation target sequencing) or (confirmed by immunohistochemistry)) colon adenocarcinoma.
- •The lower edge of the tumor is less than 12cm from the anus as measured by colonoscopy and MRI,or TRUS.
- •It was confirmed by magnetic resonance imaging (MRI) or intracavitary ultrasound of the rectum as T3-4 or N+, and M0 by enhanced CT.
- •The ECOG physical status score is 0-
- •Life expectancy is expected to be more than 1 year.
- •First diagnosis, no previous anti-tumor treatment received, and no chemotherapy contraindications.
- •Appropriate organ function is defined as follows: Hemoglobin level ≥ 90g/L, Neutrophil count ≥ 1.5×10^9/L, Platelet count ≥ 75×10^9/L, Serum total bilirubin ≤ 1.5× the upper limit of normal (UNL), Aspartate aminotransferase (AST) ≤ 2× UNL, Alanine aminotransferase (ALT) ≤ 3× UNL, Serum creatinine ≤ 1.5× UNL.
- •Informed consent, able to understand the study protocol and willing to participate in the study, and will provide written informed consent.
排除标准
- •Early rectal cancer (T1-2N0M0); The lower margin of the tumor was less than 5cm from the anus and T
- •APR(combined abdominal perineal resection) is required;
- •Multifocal colorectal cancer.
- •Tumor obstruction or high risk of obstruction, bleeding, and/or perforation requiring emergency surgery or stent placement.
- •Cannot tolerate chemotherapy or immunotherapy, such as but not limited to bone marrow suppression.
- •History of malignant tumors, except for basal cell carcinoma, papillary thyroid carcinoma, and various in situ cancers.
- •Acute exacerbation of important organ diseases (such as but not limited to COPD, coronary heart disease, and renal insufficiency) and/or severe acute infectious diseases (such as but not limited to hepatitis, pneumonia, and myocarditis), ASA score > 3 points.
- •Mental disorders, illiteracy, or language communication barriers that prevent the understanding of the study protocol.
- •Peripheral sensory neuropathy, unable to receive oxaliplatin-based chemotherapy.
- •Continuous use of glucocorticoids for more than 3 days within 1 month prior to signing the informed consent form, or having comorbidities requiring the use of glucocorticoid therapy.
- •Unable to undergo enhanced CT examination
- •Pregnancy or lactation.
- •Refused to participate in this study.
- •Other situations in which the researcher deems unsuitable for this study.
研究组 & 干预措施
neoadjuvant Tislelizumab combined with chemotherapy
Patients with locally advanced rectal cancer who met the inclusion criteria received two or four cycles of Tislelizumab combined Capecitabine and Oxaliplatin regimen chemotherapy and were evaluated by enhanced CT and MRI\TRUS. Then, these patients will receive curative surgery for rectal cancer.
Interventions:
Drug: Oxaliplatin Drug: Capecitabine Drug: Tislelizumab Procedure: curative surgery for rectal cancer
干预措施: Tislelizumab combined with chemotherapy (Drug)
结局指标
主要结局
Pathological complete response (pCR) rate
时间窗: 7days of postoperative pathological examination
the proportion of tumor regression grades 0 (TRG0, disappearance of tumor cells) in the pathological specimens of surgically resected tumors
次要结局
- 3-year disease-free survival(DFS) rate(36 months from date of the patient signs the informed consent form)
- 3-year overall survival(OS) rate(36 months from date of the patient signs the informed consent form)
- the rate of adverse events(AEs)(From the first day of immunotherapy until 6 months after the end of treatment)
- the rate of immune-related adverse events(irAEs)(From the first day of immunotherapy until 6 months after the end of treatment)
- the rate of R0 resection(7 days of postoperative pathological examination)
- Complete Clinical Response(cCR) rate(5 days before surgery)
- 3-year local recurrence rate(36 months from date of the patient signs the informed consent form)
- the rate of surgical complication during or after operation(From the day of surgery to 30 days after the operation)
- Retain anal proportions(immediately after the surgery)
研究者
Hui Li
Deputy chief physician
First Affiliated Hospital of Guangxi Medical University