Node-sparing Short-Course Radiation Combined With CAPOX and Tislelizumab for MSS Rectal Cancer

Phase 3RecruitingNCT06507371

Sir Run Run Shaw Hospital170 enrolled

Overview

This is a randomized, prospective, multicenter, open-label, Phase III clinical trial to evaluate node-sparing modified short-course radiation (Radiation targeting the tumor bed without irradiating surrounding tumor-draining lymph nodes) combined with CAPOX and PD-1 Inhibitor (Tislelizumab) compared with standard short-course radiation combined with CAPOX for patients with MSS middle and low rectal cancer. A total of 170 patients will be enrolled in this trial. The primary endpoint is the rate of pathological complete response (pCR). The EFS rate, ORR, organ preservation rate, long-term prognosis, and adverse effects will also be analyzed.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

170

Conditions

Rectal Cancer

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Patients who have a strong willingness to preserve the anus and are willing to receive neoadjuvant therapy. 2. Male or Female aged 18-75. 3. 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 cT3-4bN0/+M0, and the lymph nodes are limited to the mesorectum. 4. 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. 5. Eastern Cooperative Oncology Group (ECOG) score 0-1. 6. No previous treatment (including anti-tumor therapy, immunotherapy or pelvic radiation). 7. Laboratory tests indicating no contraindications to radiotherapy, chemotherapy and immunotherapy. 8. Informed consent form signed. Exclusion Criteria: 1. Patients with a previous history of malignant tumors besides rectal cancer. 2. Patients with distant metastases before enrollment. 3. Patients with positive internal or external iliac lymph nodes are assessed by MRI or CT. 4. Patients with obstruction, perforation, or bleeding that require emergency surgery. 5. Patients with severe concomitant diseases and estimated survival time ≤ 5 years. 6. Allergic to any component of the therapy. 7. Patients who received immunosuppressive or systemic hormone therapy for immunosuppressive purposes within 1 month prior to the initiation of therapy. 8. Patients who have received any other experimental drug (including immunotherapy) or participated in another interventional clinical trial within 30 days before screening. 9. 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. 10. Patients with congenital or acquired immune deficiency (such as HIV infection). 11. Vulnerable groups, including mentally ill, cognitively impaired, critically ill patients, minors, pregnant or lactating women, illiterate, etc. 12. Other conditions that investigators consider not suitable for this study.

Outcomes

Primary Outcomes

pathological complete response (pCR) rate

Pathological complete response (pCR) rate

Time frame: within 10 days after completion of surgery

Secondary Outcomes

event free survival (EFS)

the time from randomization until relapse or progression

Time frame: 3 years after randomization

overall response rate (ORR)

The ORR represents the proportion of patients whose tumor burden decreases by a pre-defined clinically meaningful threshold and is maintained for a minimum required duration, which included complete response (CR) rate and partial response (PR) rate

Time frame: within 10 days after completion of chemotherapy

organ preservation rate

patients who are able to retain their rectum/anal sphincter after treatment, without requiring a permanent colostomy.

Time frame: within 10 days after completion of chemotherapy

Disease free survival(DFS)

The three-year disease-free survival of patients.

Time frame: 3 years after chemotherapy or surgery

Overall survival(OS）

The three-year overall survival of patients.

Time frame: 3 years after chemotherapy or surgery

Adverse effects rate

Rate of radiotherapy, chemotherapy and immunotherapy related adverse events

Time frame: From date of initiation of treatment until the date of death from any cause, assessed up to 5 years

Rectal specific quality of life assessment via QLQ-CR29 Rectal specific quality of life assessment via QLQ-CR29 Rectal specific quality of life assessment via QLQ-CR29

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.

Time frame: Baseline and months 3, 6, 12, 24, 36, 60 after the chemotherapy or surgery

Quality of life assessment via QLQ-C30

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

Time frame: Baseline and months 3, 6, 12, 24, 36, 60 after the chemotherapy or surgery

Validation of the Wexner score

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.

Time frame: Baseline and months 3, 6, 12, 24, 36, 60 after the chemotherapy or surgery

Central Contacts

Zhangfa Song, M.D, PH.D

CONTACT

+86 13867421652 songzhangfa@zju.edu.cn

Cheng Cai, M.D

CONTACT

18395995912 ColoSurg_cc@zju.edu.cn

Node-sparing Short-Course Radiation Combined With CAPOX and Tislelizumab for MSS Rectal Cancer

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts