Total Neoadjuvant Treatment With or Without Tislelizumab for Locally Advanced Rectal Cancer.
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
Sponsorbrenner baruch
About this trial
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 criteria
This trial does not accept healthy volunteersQualifiers
Subjects with histologically confirmed primary (non-recurrent) LARC (tumor 12 cm or less from the anal verge, as assessed by rigid proctoscopy), stage T3-4 N0 or TX N+ according to base-line pelvic MRI and PET-CT.
Patients who are planned for TNT 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.
Disqualifiers
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.
Medical history of vasculitis.
Prior organ transplant, including allogenic bone marrow transplantation.
Grade > 1 peripheral sensory neuropathy.
Trial design
Design model
Parallel
Treatments tested in this trial
Tislelizumab
DrugDuring ChemoImmunotherapy: Patients in the investigational arm will receive 8 cycles of tislelizumab 150 mg IV on Day 1, followed by mFOLFOX6 (Q2W).
Total neoadjuvant therapy (TNT)
DrugPatients will be treated with 6 weeks of capecitabine-based CRT followed 4 weeks later by 16 weeks of chemotherapy with mFOLFOX6, Q2W.
Treatment groups
134 Participants
are divided into 2 treatment groupsGroup A: TNT with ImmunotherapyExperimental treatment 1 intervention
Group B: TNTOther 1 intervention
Trial outcomes
Primary outcomes
1
3-year total mesorectal excision (TME) free survival rates
3-year TME free survival will be defined as the percentage of patients who are alive and did not undergo total mesorectal excision (TME) surgery, or did not have an event of loco-regional failure, metastatic recurrence or the appearance of a secondary CRC, at 36 months of follow up.
Time frame
Time from the date of registration to the date of TME or the first event of loco-regional failure, metastatic recurrence, the appearance of a secondary CRC or death from any cause. Assessed up to 36 months.Secondary outcomes
1
3 year TME-free survival rates of the CPS positive population
3-year TME free survival will be defined as the percentage of patients with CPS positive tumors (PDL-1 combined positive score \>1%), who are alive and did not undergo total mesorectal excision (TME) surgery, or did not have an event of loco-regional failure, metastatic recurrence or the appearance of a secondary CRC, at 36 months of follow up.
Time frame
Time from the date of registration to the date of TME or the first event of loco-regional failure, metastatic recurrence, the appearance of a secondary CRC or death from any cause. Assessed up to 36 months.2
Incidence of Treatment-Emergent Adverse Events (Safety)
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0"
Time frame
Time from screening until the end of study drug administration, Immune-related AEs will be recorded up to 90 days (+7 days) after the last dose of tislelizumab. Assessed up to 11 months.3
Disease-free survival (DFS)
DFS will be censored for patients who are alive and free of progression at the time of last follow-up. DFS rate will be estimated using the Kaplan-Meier method
Time frame
Time from the date of registration to the date of the first event of loco-regional failure, metastatic recurrence, the appearance of a secondary CRC or death from any cause, assessed up to 36 months4
Overall survival (OS)
Patients who are still alive when last traced will be censored at the date of last follow-up. OS rate will be estimated using the Kaplan-Meier method.
Time frame
The time interval between the day of registration and the date of death of any cause, assessed up 60 months.Sponsors and contacts
Click on the lead sponsor to view all of their trials.
brenner baruch
Lead sponsor
Rabin Medical Center
Sponsor institution
Johannes Gutenberg University Mainz
Collaborator
Source ClinicalTrials.gov