RecruitingPhase 2NCT06940388

Total Neoadjuvant Treatment With or Without Tislelizumab for Locally Advanced Rectal Cancer.

Total Neoadjuvant Treatment With or Without Tislelizumab for Locally Advanced Rectal Cancer: An Open-label Randomized Controlled Phase II Study (The TOTAL Trial)

Sponsor

brenner baruch

Enrollment

134 participants

Start Date

Jul 23, 2025

Study Type

INTERVENTIONAL

Conditions

Locally Advanced Rectal Cancer (LARC)

Summary

This prospective, multi-center, phase II randomized controlled trial will evaluate the actual benefit of adding immunotherapy with tislelizumab to the currently most effective approach against LARC, namely TNT. In this trial, we will harness several elements that may each potentially contribute to an overall high efficacy, at least in local outcomes: nCRT rather than SCRT, full length (8 cycles of mFOLFOX6) of consolidation chemotherapy, CIMT following nCRT (exploiting the upregulation of the immune response induced by the latter) and tislelizumab (with its theoretical advantage over other CPIs). In line with the changing treatment paradigms in LARC, in which high therapeutic efficacy translates into the possibility to avoid TME, the trial will have a novel primary endpoint of long-term unmaintained cCR, i.e. 3 year TME-free survival.

Eligibility

Min Age: 18 Years

Plain Language Summary

Simplified for easier understanding

This trial is testing whether adding an immunotherapy drug (tislelizumab) to the standard combination treatment — chemotherapy plus radiation — before surgery improves outcomes for patients with locally advanced rectal cancer. **You may be eligible if...** - You have been diagnosed with locally advanced rectal cancer (confirmed by biopsy) that has not yet been treated - Your tumor is within 12 cm of the anal opening - You are aged 18 or older and are healthy enough for surgery - You have not had any prior chemotherapy, radiation, or surgery for rectal cancer - Your blood counts and organ function are within acceptable ranges **You may NOT be eligible if...** - You have had previous pelvic radiation for any reason - You have active autoimmune disease - You have received prior immunotherapy or are on immunosuppressive drugs - You have serious heart, liver, or kidney problems Talk to your doctor to see if this trial is right for you.

This is a simplified summary. Always discuss eligibility with your doctor before enrolling in a clinical trial.

Print for Your Doctor Check Your Eligibility

Interested in this trial?

Get notified about updates and connect with the research team.

Interventions

DRUGTislelizumab

During ChemoImmunotherapy: Patients in the investigational arm will receive 8 cycles of tislelizumab 150 mg IV on Day 1, followed by mFOLFOX6 (Q2W).

DRUGTotal neoadjuvant therapy (TNT)

Patients will be treated with 6 weeks of capecitabine-based CRT followed 4 weeks later by 16 weeks of chemotherapy with mFOLFOX6, Q2W.

Locations(2)

Johannes Gutenberg-University Clinic, Mainz, Germany 1.Dept. Medicine, Prof. Peter R. Galle

Mainz, Germany

Davidoff Cancer Center, Rabin Medical Center, Beilinson Hospital

Petah Tikva, Israel

View Full Details on ClinicalTrials.gov

For the most up-to-date information, visit the official listing.

Visit

NCT06940388

Related Trials

NG-350A Plus Chemoradiotherapy for Locally Advanced Rectal Cancer

NCT064598696 locations

Application and Exploration of Personalized ctDNA-MRD Detection Technology in Predicting the Efficacy of Neoadjuvant Therapy for Rectal Cancer

NCT073930481 location

SCRT Combined With Chemotherapy and Iparomlimab and Tuvonralimab in MSS or pMMR Patients With Locally Advanced Rectal Cancer

NCT068640131 location

A Single-center, Phase II Study on Efficacy & Safety of SCRT+CAPOX+Serplulimab+Bevacizumab for MSS Rectal Cancer

NCT073479511 location

Real-world Efficacy and Safety of Neoadjuvant Dostarlimab in Patients With dMMR/MSI-H Locally Advanced Rectal Cancer

NCT072692492 locations