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

Rectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06390982
• Other study ID #: BGB-A317-2011-IIT
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: May 2024
• Est. completion date: December 2028

Study information

• Verified date: April 2024
• Source: Fudan University
• Contact: Min Jian Xu, MD
• Phone: 86-21-64041990
• Email: xujmin[@]aliyun.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 46
• Est. completion date: December 2028
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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 > 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

Related Conditions & MeSH terms

• Rectal Cancer
• RECTAL NEOPLASMS

Intervention

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

Drug:
• Tislelizumab
200 mg IV on Day 1 of each 21-day cycle.
• Capecitabine
Capecitabine 1000 mg/m2 orally twice daily (bid) on Day 1 to 14 of each 21-day cycle in CAPOX regimen
• Oxaliplatin
130 mg/m2 IV on Day 1 of each 21-day cycle in CAPOX regimen
• Capecitabine
825 mg/m2 orally twice daily (bid) 5 days/week during radiotherapy.

Locations

Country	Name	City	State
n/a

Sponsors (8)

Lead Sponsor	Collaborator
Fudan University	First Hospital of China Medical University, Huadong Hospital, Liaoning Cancer Hospital & Institute, RenJi Hospital, Shanghai Changzheng Hospital, Shanghai Zhongshan Hospital, The Fourth Hospital of Hebei Medical University

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	1/2/3 year organ-preservation rate	defined as the proportion of participants who survived and did not underwent TME in 1/2/3 year (in the CR set and full analysis set respectively)	From first dose of radiotherapy up to 36 months, approximately
Secondary	1/2/3 year EFS rate	defined as the proportion of participants who did not develop local recurrence, distant metastasis, new invasive primary lesions of colorectal cancer, or death in 1/2/3 year (in the CR set, non-CR set and full analysis set respectively)	From first dose of radiotherapy up to 36 months, approximately
Secondary	1/2/3 year OS rate	defined as the proportion of participants who survived in 1/2/3 year (in the full analysis set)	From first dose of radiotherapy up to 36 months, approximately
Secondary	Percentage of Participants With Adverse Events	Percentage of Participants With adverse events (AEs) , immune-related adverse events(irAE) and serious adverse events (SAEs) per the National Cancer Institute CommonTerminology Criteria for Adverse Events (NCI CTCAE) Version 5.0	From first dose of radiotherapy up to 36 months, approximately