Rectal Artery Infusion Chemotherapy of Oxaliplatin Plus Capecitabine Combined With Anti-PD1 Antibody After Induction Chemotherapy for Microsatellite Stable Locally Advanced Rectal Cancer：a Prospective Single-arm Phase II Study
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 38
- 试验地点
- 1
- 主要终点
- pCR rate
研究概览
简要总结
The purpose of this study is to explore whether rectal artery infusion chemotherapy combined with anti-PD1 antibody is an effective neoadjuvant therapy for the microsatellite stable locally advanced rectal cancer.
详细描述
Neoadjuvant chemoradiation is the standard treatment for locally advanced rectal cancer. Neoadjuvant chemoradiotherapy can achieve a pathological complete response rate (pCR) of about 20%. However, radiotherapy can cause tissue edema and fibrosis, increasing the risk of anastomotic leakage, resulting in rectal, urinary, and sexual dysfunction. Neoadjuvant chemotherapy or immunotherapy can avoid these adverse reactions, but the pCR rate of chemotherapy is significantly lower than that of neoadjuvant radiotherapy, and immunotherapy is less effective for MSS patients with weak immunogenicity. This study is a prospective, single-arm, single-center trial. The study will enhance the local killing effect of oxaliplatin through rectal artery infusion and induce immunogenic cell death (ICD) to enhance tumor antigen presentation, and then combine anti-PD1 antibody for neoadjuvant therapy. The study will address whether this treatment combination achieves pCR rates that are non-inferior to neoadjuvant RT for MSS-type locally advanced rectal cancer. It is known that the effective rate of oxaliplatin-containing intravenous chemotherapy for colorectal cancer is about 60%. In this study, 2 cycles of XELOX induction chemotherapy were firstly performed to screen out patients who were sensitive to chemotherapy. These patients were then infused with oxaliplatin via the superior rectal artery and oral capecitabine, combined with anti-PD1 antibody therapy for 2 cycles, and then underwent TME surgery. The primary endpoint of the study was the pCR rate.
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
- •Pathologically diagnosed rectal adenocarcinoma
- •Age ≥18 years old and ≤75 years old
- •MRI stage T3-4aNany and TanyN1-2, but not T4b and no distant metastasis
- •Life expectancy of 1 year The above
- •Informed consent, no contraindications to chemotherapy exist
- •The distance from the lower edge of the tumor to the anus is between 5cm to 12cm by MRI
排除标准
- •Refused to participate in this study
- •Multifocal colorectal cancer
- •Past history of malignant tumors, except for basal cell carcinoma/papillary thyroid carcinoma/various types of carcinoma in situ
- •Unable to receive chemotherapy , such as but not limited to bone marrow suppression, etc
- •Major organ diseases (such as but not limited to COPD, coronary heart disease and renal insufficiency, etc.) acute attack and or severe acute infectious diseases (such as but not limited to hepatitis, pneumonia and myocarditis, etc.), ASA score> 3
- •Mental disorder or illiteracy or language and communication barriers cannot understand the research plan
- •There are contraindications to arterial puncture, such as but not limited to severe arteriosclerosis or even atresia, coagulation dysfunction, long-term use of anticoagulant drugs and cannot be stopped, etc
- •Rectal tumor has obstruction or high risk of obstruction and or there is bleeding and/or perforation
- •Peripheral sensory nerve disorder, unable to receive oxaliplatin chemotherapy
- •Lateral pelvic lymph node metastasis (mainly supplied by internal iliac artery)
- •Pregnancy or breastfeeding
- •Unable to accept MRI examination
- •Consecutive use of glucocorticoids for more than 3 days within 1 month before signing the consent form
- •Tumor directly invades or adheres to adjacent organs、structures(T4b) or tumor invaded MRF（Mesoretal Fascia）
- •Other scenarios deemed inappropriate by the investigators
研究组 & 干预措施
Rectal Artery Infusion Chemotherapy
Patients receive 2 cycles of Capecitabine and Oxaliplatin (CapeOx) chemotherapy and evaluated with rectum Magnetic Resonance Imaging (MRI). Patients with more than 20% regression of maximum diameter of rectal tumor in MRI image will entry into next step of rectal artery infusion of Oxaliplatin and oral Capecitabine（1000mg/㎡）with anti-PD1 antibody（200mg）every 3 weeks for 2 cycles.Then those patients will receive rectectomy including anterior resection or abdominoperineal resection by open or laparoscopy with TME.
干预措施: Anti-PD-1 monoclonal antibody (Drug)
Rectal Artery Infusion Chemotherapy
Patients receive 2 cycles of Capecitabine and Oxaliplatin (CapeOx) chemotherapy and evaluated with rectum Magnetic Resonance Imaging (MRI). Patients with more than 20% regression of maximum diameter of rectal tumor in MRI image will entry into next step of rectal artery infusion of Oxaliplatin and oral Capecitabine（1000mg/㎡）with anti-PD1 antibody（200mg）every 3 weeks for 2 cycles.Then those patients will receive rectectomy including anterior resection or abdominoperineal resection by open or laparoscopy with TME.
干预措施: Oxaliplatin (Drug)
Rectal Artery Infusion Chemotherapy
Patients receive 2 cycles of Capecitabine and Oxaliplatin (CapeOx) chemotherapy and evaluated with rectum Magnetic Resonance Imaging (MRI). Patients with more than 20% regression of maximum diameter of rectal tumor in MRI image will entry into next step of rectal artery infusion of Oxaliplatin and oral Capecitabine（1000mg/㎡）with anti-PD1 antibody（200mg）every 3 weeks for 2 cycles.Then those patients will receive rectectomy including anterior resection or abdominoperineal resection by open or laparoscopy with TME.
干预措施: Rectectomy (Procedure)
Rectal Artery Infusion Chemotherapy
Patients receive 2 cycles of Capecitabine and Oxaliplatin (CapeOx) chemotherapy and evaluated with rectum Magnetic Resonance Imaging (MRI). Patients with more than 20% regression of maximum diameter of rectal tumor in MRI image will entry into next step of rectal artery infusion of Oxaliplatin and oral Capecitabine（1000mg/㎡）with anti-PD1 antibody（200mg）every 3 weeks for 2 cycles.Then those patients will receive rectectomy including anterior resection or abdominoperineal resection by open or laparoscopy with TME.
干预措施: Capecitabine (Drug)
结局指标
主要结局
pCR rate
时间窗: 1 day of postoperative pathological examination.
the pathological complete remission rate of the rectal carcinoma
次要结局
- Surgical Complication(within 30 days since operation)
- DFS(From date of first chemotherapy until the date of first documented recurrence of tumor or date of death from any cause，whichever came first，assessed up to 36 months.)
- AE(From date of first chemotherapy until the date of patients were discharged from hospital after receiving TME operation, up to 20 weeks)
- low anterior resection syndrome score(3 months after operation; 6 months after operation;12 months after operation)
- Concentration of cytokines(blood test of cytokines at baseline , pre-intervention of neoadjuvant chemotherapy, pre-intervention of artery infusion chemotherapy and pre-surgery.)
- Concentration of DAMP(blood test of DAMP at baseline , pre-intervention of neoadjuvant chemotherapy, pre-intervention of artery infusion chemotherapy and pre-surgery.)
- Concentration of FLT3LG(blood test of FLT3LG at baseline , pre-intervention of neoadjuvant chemotherapy, pre-intervention of artery infusion chemotherapy and pre-surgery.)