Node-sparing Short-Course Radiation Combined With CAPOX and Tislelizumab for MSS Rectal Cancer (mRCAT-III)

Zhejiang University

Status and phase: Enrolling; Phase 3

Conditions: Rectal Cancer

Treatments: Radiation: node-sparing modified short-course radiotherapy; Drug: Capecitabine; Drug: Oxaliplatin; Drug: PD-1 antibody; Radiation: standard short-course radiotherapy

Study type: Interventional

Funder types: Other

Identifiers

NCT06507371

SRRS-mRCA-III

Details and patient eligibility

About

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.

Enrollment: 170 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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170 participants in 3 patient groups

Treatment Arm

Experimental group

Description:

Participants will receive 5\*5Gy node-sparing modified short-course radiation (radiation targeting the tumor bed without irradiating surrounding tumor-draining lymph nodes) concurrently with CAPOX and tislelizumab regimens: Oxaliplatin, 130mg/m2, intravenous infusion,d1 of each cycle; Capecitabine, 1000mg/m2, PO, BID, d1-14 and tislelizumab, 200mg intravenous infusion d1 of each cycle. CAPOX and tislelizumab repeat every 3 weeks for 4 cycles. After treatment, digital rectal examination, pelvic MRI, endoscopy, and biopsy will be performed to evaluate the tumor regression grade. Patients will receive TME surgery after the chemo-immunotherapy, pCR rate and TRG grade will be evaluated.

Treatment:

Drug: PD-1 antibody

Drug: Oxaliplatin

Drug: Capecitabine

Radiation: node-sparing modified short-course radiotherapy

Standard Arm

Experimental group

Description:

Participants will receive 5\*5Gy standard short-course radiation (radiation targeting the tumor bed and surrounding tumor-draining lymph nodes) concurrently with CAPOX regimens: Oxaliplatin, 130mg/m2, intravenous infusion,d1 of each cycle; Capecitabine, 1000mg/m2, PO, BID, d1-14. CAPOX repeat every 3 weeks for 4 cycles. After treatment, digital rectal examination, pelvic MRI, endoscopy, and biopsy will be performed to evaluate the tumor regression grade. Patients will receive TME surgery after the chemo-immunotherapy, pCR rate and TRG grade will be evaluated.

Treatment:

Radiation: standard short-course radiotherapy

Drug: Oxaliplatin

Drug: Capecitabine

Exploration Arm

Other group

Description:

Participants will receive 5\*5Gy standard short-course radiation (radiation targeting the tumor bed and surrounding tumor-draining lymph nodes) concurrently with CAPOX and tislelizumab regimens: Oxaliplatin, 130mg/m2, intravenous infusion,d1 of each cycle; Capecitabine, 1000mg/m2, PO, BID, d1-14 and tislelizumab, 200mg intravenous infusion d1 of each cycle. CAPOX and tislelizumab repeat every 3 weeks for 4 cycles. After treatment, digital rectal examination, pelvic MRI, endoscopy, and biopsy will be performed to evaluate the tumor regression grade. Patients will receive TME surgery after the chemo-immunotherapy, pCR rate and TRG grade will be evaluated.

Treatment:

Radiation: standard short-course radiotherapy

Drug: PD-1 antibody

Drug: Oxaliplatin

Drug: Capecitabine