Neoadjuvant Chemoradiotherapy Followed by Chemotherapy With or Without Tislelizumab for Resectable Ultra-low Rectal Cancer: The RELIEVE-02 Study

Not Applicable

Not yet recruiting

• Conditions: Rectal Cancer
• Interventions: Radiation: Long-course chemoradiotherapy; Drug: Tislelizumab combined with the CAPOX regimen; Drug: CAPOX regimen

• Registration Number: NCT07132463
• Lead Sponsor: Fudan University

Brief Summary

This open-label, multicenter, randomized controlled trial involved 154 patients with pathologically confirmed, previously untreated, resectable MSI-L or MSS/pMMR ultra-low rectal adenocarcinoma. Patients were randomly assigned (1:1) to two groups to receive concurrent chemoradiotherapy followed by 4-6 cycles of chemotherapy ± tislelizumab. After treatment, patients who achieved complete clinical response (cCR), including those who reached pCR after local excision, or near cCR with pCR after local excision, were recommended to continue with 4-2 cycles of chemotherapy ± tislelizumab, followed by a watch-and-wait approach. Patients evaluated as incomplete responders were recommended for total mesorectal excision (TME) surgery. The primary endpoint is the anus preservation rate, while secondary endpoints include CR rate, 1-year/2-year/3-year organ preservation rates, 1-year/2-year/3-year EFS rates, and 1-year/2-year/3-year OS rates, etc.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-08
• Study Start: 2025-08-01
• Study First Submitted: 2025-08-12
• Study First Submitted QC: 2025-08-18
• Last Update Submitted: 2025-08-18
• Study First Posted: 2025-08-20
• Last Update Posted: 2025-08-20
• Primary Completion: 2027-12
• Study Completion: 2030-12-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 154

Inclusion Criteria

1. Able to provide written informed consent, understand, and comply with the requirements and evaluation schedule.
2. Age ≥18 and ≤75 years old.
3. Histologically confirmed rectal adenocarcinoma.
4. Immunohistochemistry confirmed pMMR (positive for MLH1, MSH2, MSH6, and PMS2), or PCR/NGS confirmed MSI-L or MSS.
5. Tumor distal margin confirmed to be ≤ 3 cm from the anal verge by colonoscopy, digital rectal examination, or MRI.
6. Clinical stage cT1-3N1M0 or cT3N0M0 (the 8th UICC/AJCC; T and N evaluated by MRI).
7. Resectable primary tumor assessed by the Investigator.
8. No prior anti-tumor treatment for rectal cancer.
9. Eastern Cooperative Oncology Group (ECOG) performance status score ≤ 1.
10. Adequate organ function.
11. 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 for 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.

Exclusion Criteria

1. Histologically confirmed poorly differentiated/undifferentiated adenocarcinoma, mucinous adenocarcinoma, or signet ring cell carcinoma.
2. Previously received treatment for rectal cancer or have evidence of distant metastasis.
3. Presence of the following high-risk factors assessed by MRI: MRF+, EMVI+, cN2, positive lateral lymph nodes, T3d.
4. Presence of or at high risk for obstruction, perforation, or bleeding.
5. Unsuitability for long-course radiotherapy.
6. Inability to tolerate surgery.
7. ≥ 2 colorectal cancer lesions at the same time.
8. Contraindications for MRI examination.
9. Other malignant tumors in the past or currently present.
10. Active autoimmune disease requiring systemic therapy within the past 2 years.
11. HIV infection.
12. Untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers (HBV DNA > 500 IU/mL) or active HCV carriers with detectable HCV RNA.
13. Hypersensitivity to any ingredient of tislelizumab, capecitabine, and oxaliplatin, or to any component of their containers.
14. Other conditions judged by the researcher as not meeting the enrollment requirements.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Concurrent Chemoradiotherapy Followed by Chemotherapy Plus Immunotherapy Group	Long-course chemoradiotherapy	Long-course chemoradiotherapy followed by 4 cycles of CAPOX and Tislelizumab. (Note: Patients evaluated as ncCR after completion, if refusing local excision, may receive an additional 2 cycles of CAPOX and Tislelizumab before re-evaluation.)
Concurrent Chemoradiotherapy Followed by Chemotherapy Plus Immunotherapy Group	Tislelizumab combined with the CAPOX regimen	Long-course chemoradiotherapy followed by 4 cycles of CAPOX and Tislelizumab. (Note: Patients evaluated as ncCR after completion, if refusing local excision, may receive an additional 2 cycles of CAPOX and Tislelizumab before re-evaluation.)
Concurrent Chemoradiotherapy Followed by Chemotherapy Group	Long-course chemoradiotherapy	Long-course chemoradiotherapy followed by 4 cycles of CAPOX. (Note: Patients evaluated as ncCR after completion, if refusing local excision, may receive an additional 2 cycles of CAPOX before re-evaluation.)
Concurrent Chemoradiotherapy Followed by Chemotherapy Group	CAPOX regimen	Long-course chemoradiotherapy followed by 4 cycles of CAPOX. (Note: Patients evaluated as ncCR after completion, if refusing local excision, may receive an additional 2 cycles of CAPOX before re-evaluation.)

Primary Outcome Measures

Name	Time	Method
Anus preservation rate	From first dose of radiotherapy up to approximately 24/32±4 weeks.	Defined as the anus preservation rate in the efficacy-evaluable analysis set of patients, as assessed by the investigators.

Secondary Outcome Measures

Name	Time	Method
Complete Response rate (CR Rate)	From first dose of radiotherapy up to approximately 24/32±4 weeks.	Defined as the proportion of participants with clinical complete response (cCR) and pathologic complete response (pCR), determined by the investigators.
1/2/3-Year Organ-Preservation Rate	From first dose of radiotherapy up to approximately 36 months.	Defined as the proportion of participants who survived and did not undergo TME at 1, 2, and 3 years.
1/2/3-Year EFS Rate	From first dose of radiotherapy up to approximately 36 months.	Defined as the proportion of participants who did not develop local recurrence, distant metastasis, new invasive primary lesions of colorectal cancer, or death at 1, 2, and 3 years.
Percentage of Participants With Adverse Events	From first dose of radiotherapy up to approximately 36 months.	Percentage of participants with adverse events (AEs), immune-related adverse events(irAE), and serious adverse events (SAEs).
1/2/3-Year OS Rate	From first dose of radiotherapy up to approximately 36 months.	Defined as the proportion of participants who survived at 1, 2, and 3 years.