Locally Advanced Rectal Cancer (LARC)Phase 2TOTALNCT06940388
Total Neoadjuvant Treatment With or Without Tislelizumab for Locally Advanced Rectal Cancer.
A Phase 2 study testing Tislelizumab and Total neoadjuvant therapy (TNT) in people with Locally Advanced Rectal Cancer (LARC), run by brenner baruch at 2 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Locally Advanced Rectal Cancer (LARC)
- What is being tested?
- Tislelizumab and Total neoadjuvant therapy (TNT)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 134 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 23 Jul 2025to Aug 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- Able to provide the FFPE block or 10 unstained slides from the colonoscopy for confirmation of the diagnosis, CPS status and for investigational purposes.
- Age 18 years or more.
Show all 14Show fewer
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) < 2.
- Screening laboratory values must meet the following criteria (using CTCAEv5.0):
- WBC > 2000/µL ii) Neutrophils > 1500/ µL iii) Platelets > 100 x 103/ 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.
- 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.
Who cannot join
- 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.
- 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).
Show all 9Show fewer
- 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.
- 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.
Trial locations and contacts
2 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
2 sites in 2 countries
Germany1 site, 1 recruiting
- Not yet recruiting
Johannes Gutenberg-University Clinic, Mainz, Germany 1.Dept. Medicine, Prof. Peter R. Galle
Mainz
Israel1 site, 1 recruiting
- Recruiting
Davidoff Cancer Center, Rabin Medical Center, Beilinson Hospital
Petah Tikva
About this study
Official title: Total Neoadjuvant Treatment With or Without Tislelizumab for Locally Advanced Rectal Cancer: An Open-label Randomized Controlled Phase II Study (The TOTAL 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.
Read the detailed description
This is a prospective, multi-center, double arm, open-label, phase II randomized (1:1) controlled trial aimed to determine the efficacy and safety of TNT with or without tislelizumab in patients with primary, histologically proven LARC. All subjects will undergo a screening process, based on the inclusion and exclusion criteria listed below. All subjects confirmed to be eligible will be randomized (1:1) into one of the two study arms, using an eCRF software. Patients in the investigational arm will be treated with 6 weeks of capecitabine-based CRT followed 4 weeks later by 16 weeks of CIMT with tislelizumab and mFOLFOX6, both given Q2W. Patients in the control arm will be treated with 6 weeks of capecitabine-based CRT followed 4 weeks later by 16 weeks of chemotherapy with mFOLFOX6, without tislelizumab, Q2W. Patients in both arms will be re-staged 8 weeks (+/-14 days) after the completion of therapy. Patients who will achieve cCR/near cCR will be closely followed by WW, and will undergo TME at any sign of local tumor regrowth. Patients in both arms with residual tumor, will undergo immediate TME. All patients will be followed according to current NCCN guidelines.The primary aim of the trial is to demonstrate that an approach of adding tislelizumab to the chemotherapy phase of the neoadjuvant treatment will increase the 3 year TME-free survival rate by >20%, from 50% (based on the 53% 3 year TME-free survival rate in the OPRA trial) to 70% in patients with LARC.
- Conditions
- Locally Advanced Rectal Cancer (LARC)
- Being tested
- Tislelizumab, Total neoadjuvant therapy (TNT)
- Keywords
- rectal cancer, locally advanced rectal cancer, total neoadjuvant treatment, immunotherapy
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TislelizumabDrug
During 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)Drug
Patients will be treated with 6 weeks of capecitabine-based CRT followed 4 weeks later by 16 weeks of chemotherapy with mFOLFOX6, Q2W.
| Study group | Role | What they receive |
|---|---|---|
| TNT with Immunotherapy | Experimental | Patients will be treated with 6 weeks of capecitabine-based CRT followed 4 weeks later by 16 weeks of CIMT with tislelizumab and mFOLFOX6, both given Q2W. Receives: Drug: Tislelizumab |
| TNT | Other | Patients will be treated with 6 weeks of capecitabine-based CRT followed 4 weeks later by 16 weeks of chemotherapy with mFOLFOX6, Q2W. Receives: Drug: Total neoadjuvant therapy (TNT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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 (5)
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.
Measured: 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.
Incidence of Treatment-Emergent Adverse Events (Safety)
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0"
Measured: 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.
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
Measured: 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 months
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.
Measured: The time interval between the day of registration and the date of death of any cause, assessed up 60 months.
Progression-free survival (PFS)
PFS is defined as the time from the date of registartion to the date of the first objectively documented tumor progression, or death, whichever occurs first.
Measured: The time from the date of registration to the date of the first objectively documented tumor progression, or death, whichever occurs first, assessed up to 60 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Apr 2025
- Study start23 Jul 2025
- Primary completionAug 2029 (estimated)
- Study completionAug 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (18)Papers the sponsor has linked to this study.
- Other trials for Locally Advanced Rectal Cancer (LARC)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a prospective, multi-center, double arm, open-label, phase II randomized (1:1) controlled trial aimed to determine the efficacy and safety of TNT with or without tislelizumab in patients with primary, histologically proven LARC.
- Masking
- None (open label)
- Enrolment
- 134 participants (estimated)
Sponsor and investigators
- Lead sponsor
- brenner baruch
- Sponsor type
- University, hospital or other
- Collaborators
- Johannes Gutenberg University Mainz
- Responsible party
- Sponsor-investigator, brenner baruch, Rabin Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06940388
- Sponsor's protocol ID
- TOTAL
- Acronym
- TOTAL
- Status last verified
- Jul 2025
- First submitted
- 1 Apr 2025
- Last updated
- 24 Jul 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Siegel RL, Miller KD, Fedewa SA, Ahnen DJ, Meester RGS, Barzi A, Jemal A. Colorectal cancer statistics, 2017. CA Cancer J Clin. 2017 May 6;67(3):177-193. doi: 10.3322/caac.21395. Epub 2017 Mar 1.
PubMed 28248415Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024 Jan-Feb;74(1):12-49. doi: 10.3322/caac.21820. Epub 2024 Jan 17.
PubMed 38230766Bernier L, Balyasnikova S, Tait D, Brown G. Watch-and-Wait as a Therapeutic Strategy in Rectal Cancer. Curr Colorectal Cancer Rep. 2018;14(2):37-55. doi: 10.1007/s11888-018-0398-5. Epub 2018 Mar 7.
PubMed 29576755Zhong X, Wu Z, Gao P, Shi J, Sun J, Guo Z, Wang Z, Song Y. The efficacy of adding targeted agents to neoadjuvant therapy for locally advanced rectal cancer patients: a meta-analysis. Cancer Med. 2018 Mar;7(3):565-582. doi: 10.1002/cam4.1298. Epub 2018 Feb 21.
PubMed 29464874Habr-Gama A, Perez RO, Proscurshim I, Nunes Dos Santos RM, Kiss D, Gama-Rodrigues J, Cecconello I. Interval between surgery and neoadjuvant chemoradiation therapy for distal rectal cancer: does delayed surgery have an impact on outcome? Int J Radiat Oncol Biol Phys. 2008 Jul 15;71(4):1181-8. doi: 10.1016/j.ijrobp.2007.11.035. Epub 2008 Jan 30.
PubMed 18234443Garcia-Aguilar J, Chow OS, Smith DD, Marcet JE, Cataldo PA, Varma MG, Kumar AS, Oommen S, Coutsoftides T, Hunt SR, Stamos MJ, Ternent CA, Herzig DO, Fichera A, Polite BN, Dietz DW, Patil S, Avila K; Timing of Rectal Cancer Response to Chemoradiation Consortium. Effect of adding mFOLFOX6 after neoadjuvant chemoradiation in locally advanced rectal cancer: a multicentre, phase 2 trial. Lancet Oncol. 2015 Aug;16(8):957-66. doi: 10.1016/S1470-2045(15)00004-2. Epub 2015 Jul 14.
PubMed 26187751Cercek A, Roxburgh CSD, Strombom P, Smith JJ, Temple LKF, Nash GM, Guillem JG, Paty PB, Yaeger R, Stadler ZK, Seier K, Gonen M, Segal NH, Reidy DL, Varghese A, Shia J, Vakiani E, Wu AJ, Crane CH, Gollub MJ, Garcia-Aguilar J, Saltz LB, Weiser MR. Adoption of Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer. JAMA Oncol. 2018 Jun 14;4(6):e180071. doi: 10.1001/jamaoncol.2018.0071. Epub 2018 Jun 14.
PubMed 29566109Conroy T, Bosset JF, Etienne PL, Rio E, Francois E, Mesgouez-Nebout N, Vendrely V, Artignan X, Bouche O, Gargot D, Boige V, Bonichon-Lamichhane N, Louvet C, Morand C, de la Fouchardiere C, Lamfichekh N, Juzyna B, Jouffroy-Zeller C, Rullier E, Marchal F, Gourgou S, Castan F, Borg C; Unicancer Gastrointestinal Group and Partenariat de Recherche en Oncologie Digestive (PRODIGE) Group. Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2021 May;22(5):702-715. doi: 10.1016/S1470-2045(21)00079-6. Epub 2021 Apr 13.
PubMed 33862000Galon J, Fridman WH, Pages F. The adaptive immunologic microenvironment in colorectal cancer: a novel perspective. Cancer Res. 2007 Mar 1;67(5):1883-6. doi: 10.1158/0008-5472.CAN-06-4806.
PubMed 17332313Nagtegaal ID, Marijnen CA, Kranenbarg EK, Mulder-Stapel A, Hermans J, van de Velde CJ, van Krieken JH. Local and distant recurrences in rectal cancer patients are predicted by the nonspecific immune response; specific immune response has only a systemic effect--a histopathological and immunohistochemical study. BMC Cancer. 2001;1:7. doi: 10.1186/1471-2407-1-7. Epub 2001 Jul 16.
PubMed 11481031Lin Z, Cai M, Zhang P, Li G, Liu T, Li X, Cai K, Nie X, Wang J, Liu J, Liu H, Zhang W, Gao J, Wu C, Wang L, Fan J, Zhang L, Wang Z, Hou Z, Ma C, Yang K, Wu G, Tao K, Zhang T. Phase II, single-arm trial of preoperative short-course radiotherapy followed by chemotherapy and camrelizumab in locally advanced rectal cancer. J Immunother Cancer. 2021 Nov;9(11):e003554. doi: 10.1136/jitc-2021-003554.
PubMed 34725214Zhang T, Song X, Xu L, Ma J, Zhang Y, Gong W, Zhang Y, Zhou X, Wang Z, Wang Y, Shi Y, Bai H, Liu N, Yang X, Cui X, Cao Y, Liu Q, Song J, Li Y, Tang Z, Guo M, Wang L, Li K. The binding of an anti-PD-1 antibody to FcgammaRIota has a profound impact on its biological functions. Cancer Immunol Immunother. 2018 Jul;67(7):1079-1090. doi: 10.1007/s00262-018-2160-x. Epub 2018 Apr 23.
PubMed 29687231Zitvogel L, Apetoh L, Ghiringhelli F, Kroemer G. Immunological aspects of cancer chemotherapy. Nat Rev Immunol. 2008 Jan;8(1):59-73. doi: 10.1038/nri2216.
PubMed 18097448Francisco LM, Sage PT, Sharpe AH. The PD-1 pathway in tolerance and autoimmunity. Immunol Rev. 2010 Jul;236:219-42. doi: 10.1111/j.1600-065X.2010.00923.x.
PubMed 20636820Sauer R, Becker H, Hohenberger W, Rodel C, Wittekind C, Fietkau R, Martus P, Tschmelitsch J, Hager E, Hess CF, Karstens JH, Liersch T, Schmidberger H, Raab R; German Rectal Cancer Study Group. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004 Oct 21;351(17):1731-40. doi: 10.1056/NEJMoa040694.
PubMed 15496622
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Total Neoadjuvant Treatment With or Without Tislelizumab for Locally Advanced Rectal Cancer: An Open-label Randomized Controlled Phase II Study (The TOTAL Trial)
- ClinicalTrials.gov ID
- NCT06940388
- Acronym / sponsor ID
- TOTAL / TOTAL
- Conditions
- Locally Advanced Rectal Cancer (LARC)
- Keywords
- rectal cancer, locally advanced rectal cancer, total neoadjuvant treatment, immunotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 134 participants (estimated)
- Lead sponsor
- brenner baruchUniversity, hospital or other
- Collaborators
- Johannes Gutenberg University Mainz
- Study start
- 23 Jul 2025 (actual)
- Primary completion
- Aug 2029 (estimated)
- Study completion
- Aug 2030 (estimated)
- First posted
- 23 Apr 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a prospective, multi-center, double arm, open-label, phase II randomized (1:1) controlled trial aimed to determine the efficacy and safety of TNT with or without tislelizumab in patients with primary, histologically proven LARC. All subjects will undergo a screening process, based on the inclusion and exclusion criteria listed below. All subjects confirmed to be eligible will be randomized (1:1) into one of the two study arms, using an eCRF software. Patients in the investigational arm will be treated with 6 weeks of capecitabine-based CRT followed 4 weeks later by 16 weeks of CIMT with tislelizumab and mFOLFOX6, both given Q2W. Patients in the control arm will be treated with 6 weeks of capecitabine-based CRT followed 4 weeks later by 16 weeks of chemotherapy with mFOLFOX6, without tislelizumab, Q2W. Patients in both arms will be re-staged 8 weeks (+/-14 days) after the completion of therapy. Patients who will achieve cCR/near cCR will be closely followed by WW, and will undergo TME at any sign of local tumor regrowth. Patients in both arms with residual tumor, will undergo immediate TME. All patients will be followed according to current NCCN guidelines.The primary aim of the trial is to demonstrate that an approach of adding tislelizumab to the chemotherapy phase of the neoadjuvant treatment will increase the 3 year TME-free survival rate by >20%, from 50% (based on the 53% 3 year TME-free survival rate in the OPRA trial) to 70% in patients with LARC.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This is a prospective, multi-center, double arm, open-label, phase II randomized (1:1) controlled trial aimed to determine the efficacy and safety of TNT with or without tislelizumab in patients with primary, histologically proven LARC.
| Arm | Type | Receives |
|---|---|---|
| TNT with Immunotherapy | Experimental | Drug: TislelizumabPatients will be treated with 6 weeks of capecitabine-based CRT followed 4 weeks later by 16 weeks of CIMT with tislelizumab and mFOLFOX6, both given Q2W. |
| TNT | Other | Drug: Total 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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.
- Able to provide the FFPE block or 10 unstained slides from the colonoscopy for confirmation of the diagnosis, CPS status and for investigational purposes.
Key exclusion criteria (9 listed)
- 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.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TislelizumabDuring ChemoImmunotherapy: Patients in the investigational arm will receive 8 cycles of tislelizumab 150 mg IV on Day 1, followed by mFOLFOX6 (Q2W). | Drug | TNT with Immunotherapy |
| Total 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. | Drug | TNT |
Primary outcome
3-year total mesorectal excision (TME) free survival rates
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.
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.
5 secondary outcomes
3 year TME-free survival rates of the CPS positive population
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.
Incidence of Treatment-Emergent Adverse Events (Safety)
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.
Disease-free survival (DFS)
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 months
Overall survival (OS)
Time frame: The time interval between the day of registration and the date of death of any cause, assessed up 60 months.
Progression-free survival (PFS)
Time frame: The time from the date of registration to the date of the first objectively documented tumor progression, or death, whichever occurs first, assessed up to 60 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2025.
- Background: PubMed 28248415Siegel RL, Miller KD, Fedewa SA, Ahnen DJ, Meester RGS, Barzi A, Jemal A. Colorectal cancer statistics, 2017. CA Cancer J Clin. 2017 May 6;67(3):177-193. doi: 10.3322/caac.21395. Epub 2017 Mar 1.
- Background: PubMed 38230766Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024 Jan-Feb;74(1):12-49. doi: 10.3322/caac.21820. Epub 2024 Jan 17.
- Background: PubMed 29576755Bernier L, Balyasnikova S, Tait D, Brown G. Watch-and-Wait as a Therapeutic Strategy in Rectal Cancer. Curr Colorectal Cancer Rep. 2018;14(2):37-55. doi: 10.1007/s11888-018-0398-5. Epub 2018 Mar 7.
- Background: PubMed 29464874Zhong X, Wu Z, Gao P, Shi J, Sun J, Guo Z, Wang Z, Song Y. The efficacy of adding targeted agents to neoadjuvant therapy for locally advanced rectal cancer patients: a meta-analysis. Cancer Med. 2018 Mar;7(3):565-582. doi: 10.1002/cam4.1298. Epub 2018 Feb 21.
- Background: PubMed 18234443Habr-Gama A, Perez RO, Proscurshim I, Nunes Dos Santos RM, Kiss D, Gama-Rodrigues J, Cecconello I. Interval between surgery and neoadjuvant chemoradiation therapy for distal rectal cancer: does delayed surgery have an impact on outcome? Int J Radiat Oncol Biol Phys. 2008 Jul 15;71(4):1181-8. doi: 10.1016/j.ijrobp.2007.11.035. Epub 2008 Jan 30.
- Background: PubMed 26187751Garcia-Aguilar J, Chow OS, Smith DD, Marcet JE, Cataldo PA, Varma MG, Kumar AS, Oommen S, Coutsoftides T, Hunt SR, Stamos MJ, Ternent CA, Herzig DO, Fichera A, Polite BN, Dietz DW, Patil S, Avila K; Timing of Rectal Cancer Response to Chemoradiation Consortium. Effect of adding mFOLFOX6 after neoadjuvant chemoradiation in locally advanced rectal cancer: a multicentre, phase 2 trial. Lancet Oncol. 2015 Aug;16(8):957-66. doi: 10.1016/S1470-2045(15)00004-2. Epub 2015 Jul 14.
- Background: PubMed 29566109Cercek A, Roxburgh CSD, Strombom P, Smith JJ, Temple LKF, Nash GM, Guillem JG, Paty PB, Yaeger R, Stadler ZK, Seier K, Gonen M, Segal NH, Reidy DL, Varghese A, Shia J, Vakiani E, Wu AJ, Crane CH, Gollub MJ, Garcia-Aguilar J, Saltz LB, Weiser MR. Adoption of Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer. JAMA Oncol. 2018 Jun 14;4(6):e180071. doi: 10.1001/jamaoncol.2018.0071. Epub 2018 Jun 14.
- Background: PubMed 33862000Conroy T, Bosset JF, Etienne PL, Rio E, Francois E, Mesgouez-Nebout N, Vendrely V, Artignan X, Bouche O, Gargot D, Boige V, Bonichon-Lamichhane N, Louvet C, Morand C, de la Fouchardiere C, Lamfichekh N, Juzyna B, Jouffroy-Zeller C, Rullier E, Marchal F, Gourgou S, Castan F, Borg C; Unicancer Gastrointestinal Group and Partenariat de Recherche en Oncologie Digestive (PRODIGE) Group. Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2021 May;22(5):702-715. doi: 10.1016/S1470-2045(21)00079-6. Epub 2021 Apr 13.
- Background: PubMed 17332313Galon J, Fridman WH, Pages F. The adaptive immunologic microenvironment in colorectal cancer: a novel perspective. Cancer Res. 2007 Mar 1;67(5):1883-6. doi: 10.1158/0008-5472.CAN-06-4806.
- Background: PubMed 11481031Nagtegaal ID, Marijnen CA, Kranenbarg EK, Mulder-Stapel A, Hermans J, van de Velde CJ, van Krieken JH. Local and distant recurrences in rectal cancer patients are predicted by the nonspecific immune response; specific immune response has only a systemic effect--a histopathological and immunohistochemical study. BMC Cancer. 2001;1:7. doi: 10.1186/1471-2407-1-7. Epub 2001 Jul 16.
- Background: PubMed 34725214Lin Z, Cai M, Zhang P, Li G, Liu T, Li X, Cai K, Nie X, Wang J, Liu J, Liu H, Zhang W, Gao J, Wu C, Wang L, Fan J, Zhang L, Wang Z, Hou Z, Ma C, Yang K, Wu G, Tao K, Zhang T. Phase II, single-arm trial of preoperative short-course radiotherapy followed by chemotherapy and camrelizumab in locally advanced rectal cancer. J Immunother Cancer. 2021 Nov;9(11):e003554. doi: 10.1136/jitc-2021-003554.
- Background: PubMed 29687231Zhang T, Song X, Xu L, Ma J, Zhang Y, Gong W, Zhang Y, Zhou X, Wang Z, Wang Y, Shi Y, Bai H, Liu N, Yang X, Cui X, Cao Y, Liu Q, Song J, Li Y, Tang Z, Guo M, Wang L, Li K. The binding of an anti-PD-1 antibody to FcgammaRIota has a profound impact on its biological functions. Cancer Immunol Immunother. 2018 Jul;67(7):1079-1090. doi: 10.1007/s00262-018-2160-x. Epub 2018 Apr 23.
- Individual participant dataSharing planned: Undecided
Related trials for Locally Advanced Rectal Cancer (LARC)
Active, not recruitingPhase 1
NG-350A Plus Chemoradiotherapy for Locally Advanced Rectal Cancer
Locally Advanced Rectal Cancer (LARC)
Not yet recruitingPhase 2
Combining DCSZ11 With Radiation and Chemotherapy as Neoadjuvant Treatment for pMMR Locally Advanced Rectal Cancer
Rectal Cancer
RecruitingPhase 2
NeoCSR-Omics Trial: CAPOX + Serplulimab Before vs. After Short-course RT in LARC
Rectal Cancer Patients, Locally Advanced Rectal Cancer (LARC)
Not yet recruitingPhase 2/3
Neoadjuvant Chemoradiotherapy Plus PD-1 Blockade ± CTLA-4 Blockade for High-Risk Locally Advanced Rectal Cancer (pMMR/MSS): A National Multicenter, Prospective, Randomized Controlled Trial
Locally Advanced Rectal Cancer (LARC)
Not yet recruitingPhase 2/3
Neoadjuvant Chemoradiotherapy Plus PD-1 Blockade ± CTLA-4 Blockade for Low/Intermediate-Risk Locally Advanced Rectal Cancer (pMMR/MSS): A National Multicenter, Prospective, Randomized Controlled Trial
Locally Advanced Rectal Cancer (LARC)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tislelizumab and Total neoadjuvant therapy (TNT) in people with Locally Advanced Rectal Cancer (LARC), run by brenner baruch at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 24 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Germany, Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Baruch Brenner, M.D (+972-50-4065452, brennerb@clalit.org.il), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
3-year total mesorectal excision (TME) free survival rates (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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06940388, which also lists 18 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2025.