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Total Neoadjuvant Treatment with or without Tislelizumab for Locally Advanced Rectal Cancer: An Open-label Randomized Controlled Phase II Study (The TOTAL Trial)
EU CTIS ID: 2025-522120-28-00
What this study is testing
To compare the 3-year TME-free survival of the investigational and the standard regimens
- Therapeutic exploratory (Phase II)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- • Subjects with histologically confirmed primary (non-recurrent) LARC (tumor ≤<12 cm from the anal verge, as assessed by rigid proctoscopy), stage II (T3-4 N0 M0) or stage III (TX N1-2 M0) according to base-line pelvic MRI and PET-CT.
- • Adequate contraception in fertile patients; using a highly effective method of birth control for the duration of the study, and for at least 9 months after the last dose of chemotherapy and 120 days after the last dose of immunotherapy.
- • Women of childbearing potential must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 7 days prior to the start of treatment.
- • Women must not be breastfeeding.
- • Signed written IRB approved informed consent. This must be obtained before the performance of any protocol related procedure that are not part of normal subject care. Subjects must be willing and able to comply with scheduled visits, treatments, and laboratory testing.
- • Patients who are planned for TNT (total neoadjuvant treatment) and are surgical candidates as determined by the treating physician.
You likely can't join if
- • Active or background history of an autoimmune disease except for type I diabetes mellitus, hypothyroidism requiring hormone replacement only and skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment.
- • Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
- • Known acute hepatitis B, known chronic hepatitis B infection with active untreated disease, or known active hepatitis C infection. In participants with a history of HBV or HCV, participants with detectable viral loads will be excluded.
- Current or prior use of immunosuppressive medication within 14 days before the first dose of study treatment
- Patients with mismatch repair deficient (MMRd) / microsatellite instability- high (MSI-H) tumors.
- Any evidence of interstitial lung disease or active, noninfectious pneumonitis
See the full eligibility criteria
Who can join
- • Subjects with histologically confirmed primary (non-recurrent) LARC (tumor ≤<12 cm from the anal verge, as assessed by rigid proctoscopy), stage II (T3-4 N0 M0) or stage III (TX N1-2 M0) according to base-line pelvic MRI and PET-CT.
- • Adequate contraception in fertile patients; using a highly effective method of birth control for the duration of the study, and for at least 9 months after the last dose of chemotherapy and 120 days after the last dose of immunotherapy.
- • Women of childbearing potential must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 7 days prior to the start of treatment.
- • Women must not be breastfeeding.
- • Signed written IRB approved informed consent. This must be obtained before the performance of any protocol related procedure that are not part of normal subject care. Subjects must be willing and able to comply with scheduled visits, treatments, and laboratory testing.
- • Patients who are planned for TNT (total neoadjuvant treatment) and are surgical candidates as determined by the treating physician.
- • No prior chemotherapy, immunotherapy, radiotherapy or surgery for rectal cancer.
- • No prior radiotherapy to the pelvis, for any reason.
- • Able to provide the FFPE block or 10 unstained slides from the colonoscopy for confirmation of the diagnosis, CPS (PD-L1 combined positive score) status and for investigational purposes.
- • Age ≥ > 18 years.
- • Eastern Cooperative Oncology Group (ECOG) performance status (PS) < 2.
- • Screening laboratory values must meet the following criteria (using CTCAE v5.0): i) WBC ≥ 2000/µL ii) Neutrophils ≥ 1500/ µL iii) Platelets ≥ 100 x 10^3 µL iv) Hemoglobin ≥ 9.0 g/dL v) Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 60 mL/min (using the Cockcroft Gault formula) vi) AST and ALT ≤ 2.5 x ULN vii) Total bilirubin ≤ 1.5 x ULN (total bilirubin must be < 3 x ULN for patients with Gilberts syndrome)
- • Ability to swallow tablets.
What rules you out
- • Active or background history of an autoimmune disease except for type I diabetes mellitus, hypothyroidism requiring hormone replacement only and skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment.
- • Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
- • Known acute hepatitis B, known chronic hepatitis B infection with active untreated disease, or known active hepatitis C infection. In participants with a history of HBV or HCV, participants with detectable viral loads will be excluded.
- Current or prior use of immunosuppressive medication within 14 days before the first dose of study treatment
- Patients with mismatch repair deficient (MMRd) / microsatellite instability- high (MSI-H) tumors.
- Any evidence of interstitial lung disease or active, noninfectious pneumonitis
- • Medical history of vasculitis.
- • Prior organ transplant, including allogenic bone marrow transplantation.
- • Grade > 1 peripheral sensory neuropathy.
- • Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
- • Any prior active malignancy ≤ 2 years before trial entry except for any locally recurring cancer that has been treated curatively (eg, resected basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast).
- • Any serious or uncontrolled medical disorder or active infection that, in the opinion of the investigator, may increase the risk associated with study participation, study drug administration, or would impair the ability of the subject to receive protocol therapy.
The study team makes the final eligibility decision.
Where it's taking place
- Israel
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 65+ years, 18-64 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Israel. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.