Organ Preservation With Tislelizumab and Total Neoadjuvant Therapy in Patients With Low Rectal Cancer: RELIEVE -01 Study

NCT06390982 | Not Yet Recruiting Phase 2

• 1 other identifier: BGB-A317-2011-IIT
• Study Type: interventional
• Target: 46
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is an open-label, multi-center, single-arm clinical study. All patients received concurrent chemoradiation therapy (CRT) followed by 4 cycles of tislelizumab combined with CAPOX, then underwent clinical response assessment. Patients who achieved CR (cCR+ pCR confirmed by local resection of ncCR) continue tislelizumab combined with CAPOX for another 4 cycles and tislelizumab for 9 cycles, then Watch and Wait. Patients who did not achieved CR underwent total mesorectal excision (TME).

Conditions

RECTAL NEOPLASMS; Rectal Cancer

Keywords

tislelizumab; low rectal cancer; organ preservation; watch and wait; TNT

Outcome Measures

Primary Outcomes (1)

• Complete Response rate (CR rate)

  defined as the proportion of participants with clinical complete response(cCR) or near clinical complete response (ncCR) who achieved local resection confirmed pCR determined by the investigators after CRT and 4 cycles of CAPOX plus tislelizumab.

  From first dose up to 12 months, approximately

Secondary Outcomes (4)

• 1/2/3 year organ-preservation rate

  From first dose of radiotherapy up to 36 months, approximately

• 1/2/3 year EFS rate

  From first dose of radiotherapy up to 36 months, approximately

• 1/2/3 year OS rate

  From first dose of radiotherapy up to 36 months, approximately

• Percentage of Participants With Adverse Events

  From first dose of radiotherapy up to 36 months, approximately

Study Arms (1)

tislelizumab

EXPERIMENTAL

CRT followed by 4 cycles of tislelizumab plus CAPOX and clinical response assessment: participants with CR (cCR+ pCR confirmed by local resection of ncCR): another 4 cycles of tislelizumab plus CAPOX and 9 cycles of tislelizumab, then watch and wait. participants with non-CR: underwent TME

Radiation: Radiotherapy; Drug: Tislelizumab; Drug: Capecitabine; Drug: Oxaliplatin

Interventions

Radiotherapy RADIATION

45-50.4Gy in 25-28 fractions to the pelvis on Days 1-5 every week.

tislelizumab

Tislelizumab DRUG

200 mg IV on Day 1 of each 21-day cycle.

tislelizumab

Capecitabine DRUG

Capecitabine 1000 mg/m2 orally twice daily (bid) on Day 1 to 14 of each 21-day cycle in CAPOX regimen

tislelizumab

Oxaliplatin DRUG

130 mg/m2 IV on Day 1 of each 21-day cycle in CAPOX regimen

tislelizumab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to provide written informed consent, understand and comply with the requirements and evaluation schedule
• ≥18, ≤75 years old
• Histologically confirmed rectal adenocarcinoma
• immunohistochemistry confirmed pMMR (positive for MLH1, MSH2, MSH6 and PMS2), or PCR /NGS confirmed MSI-L or MSS
• The distance from the lower edge of the tumor to the anal verge is ≤5 cm through colonoscopy, digital anal examination or MRI
• clinical stage cT1-3N1M0 or cT2-3N0M0 (the 8th UICC/AJCC; T and N is evaluated by MRI)
• Resectable primary tumor assessed by the Investigator
• Have not received any anti-tumor treatment for rectal cancer
• ECOG PS ≤ 1
• Adequate organ function
• 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 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.

You may not qualify if:

• Histologically confirmed poorly differentiated/undifferentiated adenocarcinoma, mucinous adenocarcinoma and signet ring cell carcinoma
• Have received any treatments for rectal cancer, or evidence of distant metastasis
• Presence of following high risk factors assessed by MRI: MRF +, EMVI+, cN2, Positive lateral lymph nodes, T3d
• Presence or in high risk of obstruction, perforation or bleeding;
• Not suitable for long-course radiotherapy
• Cannot tolerate surgery
• ≥2 colorectal cancer lesions at the same time
• Contraindications for MRI examination
• Other malignant tumors in the past or at the same time
• Have an active autoimmune disease requiring systemic therapy within the past 2 years
• HIV infection
• Untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers (HBV DNA \> 500 IU/mL) or active HCV carriers with detectable HCV RNA;
• Hypersensitivity to any ingredient of tislelizumab, capecitabine, and oxaliplatin or to any component of the container
• Other conditions judged by the researcher that do not meet the enrollment requirements

Sponsors & Collaborators

• Fudan University: lead
• Shanghai Zhongshan Hospital: collaborator
• Shanghai Changzheng Hospital: collaborator
• Huadong Hospital: collaborator
• RenJi Hospital: collaborator
• Hebei Medical University Fourth Hospital: collaborator
• First Hospital of China Medical University: collaborator
• Liaoning Cancer Hospital & Institute: collaborator

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Radiotherapy; tislelizumab; Capecitabine; Oxaliplatin

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Organic Chemicals

Central Study Contacts

Min Jian Xu, MD

CONTACT

86-21-64041990; xujmin@aliyun.com

Tao Wen Tang, MD

CONTACT

Tangwt1988@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: April 26, 2024
• First Posted: April 30, 2024
• Study Start: May 1, 2024
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2028
• Last Updated: April 30, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share