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

NCT ID: NCT07132463

Last Updated: 2025-08-20

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 154 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-08-31
• Study Completion Date: 2030-12-31

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.

Conditions

Rectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Concurrent Chemoradiotherapy Followed by Chemotherapy Plus Immunotherapy Group

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.)

Group Type: EXPERIMENTAL

Long-course chemoradiotherapy

Intervention Type: RADIATION

45-50.4 Gy in 25-28 fractions to the pelvis on Days 1-5 each week. Capecitabine at a dose of 825 mg/m², taken orally twice daily (bid), 5 days per week during radiotherapy.

Tislelizumab combined with the CAPOX regimen

Intervention Type: DRUG

Tislelizumab 200 mg IV on Day 1 of each 21-day cycle. Capecitabine: 1000 mg/m² orally twice daily (bid) on Days 1-14 of each 21-day cycle.

Oxaliplatin: 130 mg/m² IV on Day 1 of each 21-day cycle.

Concurrent Chemoradiotherapy Followed by Chemotherapy Group

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.)

Group Type: ACTIVE_COMPARATOR

Long-course chemoradiotherapy

Intervention Type: RADIATION

45-50.4 Gy in 25-28 fractions to the pelvis on Days 1-5 each week. Capecitabine at a dose of 825 mg/m², taken orally twice daily (bid), 5 days per week during radiotherapy.

CAPOX regimen

Intervention Type: DRUG

Capecitabine: 1000 mg/m² orally twice daily (bid) on Days 1-14 of each 21-day cycle.

Oxaliplatin: 130 mg/m² IV on Day 1 of each 21-day cycle.

Interventions

Long-course chemoradiotherapy

45-50.4 Gy in 25-28 fractions to the pelvis on Days 1-5 each week. Capecitabine at a dose of 825 mg/m², taken orally twice daily (bid), 5 days per week during radiotherapy.

Intervention Type: RADIATION

Tislelizumab combined with the CAPOX regimen

Tislelizumab 200 mg IV on Day 1 of each 21-day cycle. Capecitabine: 1000 mg/m² orally twice daily (bid) on Days 1-14 of each 21-day cycle.

Oxaliplatin: 130 mg/m² IV on Day 1 of each 21-day cycle.

Intervention Type: DRUG

CAPOX regimen

Capecitabine: 1000 mg/m² orally twice daily (bid) on Days 1-14 of each 21-day cycle.

Oxaliplatin: 130 mg/m² IV on Day 1 of each 21-day cycle.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fudan University

OTHER

Sponsor Role: lead

Responsible Party

Xu jianmin

Chief Physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Central Contacts

Jianmin Xu, MD

Role: CONTACT

xujmin@aliyun.com

86-21-64041990

Wentao Tang, MD

Role: CONTACT

tangwt1988@163.com

Other Identifiers

RELIEVE-02

Identifier Type: -

Identifier Source: org_study_id