Clinical trial NCT06390982: Organ Preservation With Tislelizumab and Total Neoadjuvant Therapy in Patients With Low Rectal Cancer: RELIEVE -01 Study
Official title: A Single-arm, Multicenter, Phase II Clinical Study of Chemoradiotherapy Followed by Tislelizumab Combined With Chemotherapy for Organ Preservation in Resectable Low Rectal Cancer：the RELIEVE-01 Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: RECTAL NEOPLASMS
Rectal Cancer
Keywords: tislelizumab
low rectal cancer
organ preservation
watch and wait
TNT
Lead sponsor: Fudan University
Sponsor class: OTHER
Collaborators: name: Shanghai Zhongshan Hospital
name: Shanghai Changzheng Hospital
name: Huadong Hospital
name: RenJi Hospital
name: Hebei Medical University Fourth Hospital
name: First Hospital of China Medical University
name: Liaoning Cancer Hospital & Institute
First posted: 2024-04-30
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


Eligibility criteria: Inclusion Criteria:

1. Able to provide written informed consent, understand and comply with the requirements and evaluation schedule
2. ≥18, ≤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. The distance from the lower edge of the tumor to the anal verge is ≤5 cm through colonoscopy, digital anal examination or MRI
6. clinical stage cT1-3N1M0 or cT2-3N0M0 (the 8th UICC/AJCC; T and N is evaluated by MRI)
7. Resectable primary tumor assessed by the Investigator
8. Have not received any anti-tumor treatment for rectal cancer
9. ECOG PS ≤ 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 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 and signet ring cell carcinoma
2. Have received any treatments for rectal cancer, or evidence of distant metastasis
3. Presence of following high risk factors assessed by MRI: MRF +, EMVI+, cN2, Positive lateral lymph nodes, T3d
4. Presence or in high risk of obstruction, perforation or bleeding;
5. Not suitable for long-course radiotherapy
6. Cannot tolerate surgery
7. ≥2 colorectal cancer lesions at the same time
8. Contraindications for MRI examination
9. Other malignant tumors in the past or at the same time
10. Have an 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 \&amp;gt; 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 the container
14. Other conditions judged by the researcher that do not meet the enrollment requirements

Primary outcomes:
measure: Complete Response rate (CR rate)
timeFrame: From first dose up to 12 months, approximately
Secondary outcomes:
measure: 1/2/3 year organ-preservation rate
timeFrame: From first dose of radiotherapy up to 36 months, approximately
measure: 1/2/3 year EFS rate
timeFrame: From first dose of radiotherapy up to 36 months, approximately
measure: 1/2/3 year OS rate
timeFrame: From first dose of radiotherapy up to 36 months, approximately
measure: Percentage of Participants With Adverse Events
timeFrame: From first dose of radiotherapy up to 36 months, approximately
Other outcomes:
Locations:
Study officials:
References: