Colorectal CancerPhase 3AtezoTRIBE2NCT06733038
FOLFOXIRI Plus Bevacizumab With or Without Atezolizumab as 1st Line Treatment of pMMR and IS IC-High Metastatic Colorectal Cancer Patients.
A Phase 3 study testing Atezolizumab, Bevacizumab and Irinotecan (CPT-11) in people with Colorectal Cancer, run by Gruppo Oncologico del Nord-Ovest at 24 sites in Italy.
Trial summary
The aim of this study is to evaluate the efficacy of the addition of Atezolizumab to FOLFOXIRI plus bevacizumab as first line treatment of patients with pMMR and Immunoscore IC-high metastatic colorectal cancer in terms of Progression Free Survival (PFS). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- Atezolizumab, Bevacizumab and Irinotecan (CPT-11)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 238 participants
- Where
- 24 sitesItaly
- Study dates
- 15 Nov 2024to 1 Apr 2029
- Phase
- Phase 3
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically proven diagnosis of colorectal cancer;
- Initially unresectable metastatic colorectal cancer not previously treated with chemotherapy for metastatic disease;
- Proficient mismatch repair (pMMR) status in tumour tissue (primary or metastatic), as determined by a local laboratory assay in a CLIA- or similarly certified;
- Immunoscore IC-high status in tumour tissue (primary or metastatic), as determined by a sponsor-defined central laboratory (HEGP, AP-HP, INSERM, France).
- At least one measurable lesion according to RECIST criteria (version 1.1);
- Availability of adequate tumour specimen (primary or metastatic);
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- Male or female of 18-75 years of age;
- ECOG PS ≤ 2 if aged < 71 years, ECOG PS = 0 if aged 71-75 years;
- Life expectancy of at least 12 weeks;
- Previous adjuvant chemotherapy allowed only if with fluoropyrimidine monotherapy and more than 6 months elapsed between the end of adjuvant and first relapse;
- Neutrophils >1.5 x 109/L, Platelets >100 x 109/L, Hb >9 g/dl;
- Total bilirubin ≤1.5 times the upper-normal limits (UNL) of the normal values and AST (SGOT) and/or ALT (SGPT) <2.5 x UNL (or <5 x UNL in case of liver metastases) alkaline phosphatase <2.5 x UNL (or <5 x UNL in case of liver metastases);
- Creatinine clearance ≥50 mL/min or serum creatinine ≤1.5 x UNL;
- INR or aPTT ≤1.5 x ULN. This applies only to patients who are not receiving therapeutic anticoagulation;
- Urine dipstick of proteinuria <2+. Patients discovered to have 2+ proteinuria on dipstick urinalysis at baseline, should undergo a 24-hour urine collection and must demonstrate ≤1 g of protein/24 h;
- Women of childbearing potential must have a negative blood pregnancy test at the baseline visit. For this trial, women of childbearing potential are defined as all women following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient;
- Male subjects with female partners of childbearing potential and female subjects of childbearing potential must, therefore, be willing to use adequate contraception as approved by the investigator (barrier contraceptive measure or oral contraception) and outlined in "Section 6.5 - Contraception", starting with the first dose of study therapy through 6 months after the last dose of bevacizumab and fluorouracil and within 5 months after the last dose of atezolizumab.
- Females of childbearing potential must have a negative blood pregnancy test at the baseline visit (i.e., performed maximum 7 days before the treatment start);
- Will and ability to comply with the protocol;
- Written informed consent to study procedures.
Who cannot join
- Radiotherapy to any site within 4 weeks before the study;
- Previous adjuvant oxaliplatin-containing chemotherapy;
- Previous treatment with bevacizumab;
- Prior treatment with CD137 agonists, anti-CTLA4, anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents;
- Complete dihydropyrimidine dehydrogenase (DPYD) deficiency (homozygous of the following DPYD polymorphisms: c1679GG, c1905+1AA, c2846TT);
- Untreated brain metastases or spinal cord compression or primary brain tumours;
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- History or evidence upon physical examination of CNS disease unless adequately treated;
- History of haemoptysis ≥ 2 grade NCIC-CTG criteria within one month prior to screening;
- Active or untreated CNS metastases:
- Symptomatic peripheral neuropathy > 2 grade NCIC-CTG criteria;
- Serious, non-healing wound, ulcer, or bone fracture;
- Evidence of bleeding diathesis or coagulopathy;
- Uncontrolled hypertension (SBP>150 mmHg and/or DPB>100 mmHg), or prior history of hypertensive crisis, or hypertensive encephalopathy ;
- Clinically significant (i.e., active) cardiovascular disease for example cerebrovascular accidents (within 6 months prior to study enrollment), myocardial infarction (within 6 months prior to study enrollment), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication;
- Significant vascular disease (e.g. aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months of study enrolment;
- Active infection requiring antibiotics at the time of initiation of study treatment;
- Any previous venous thromboembolism ≥ NCI CTCAE Grade 4;
- History of abdominal fistula, GI perforation, intra-abdominal abscess or active GI bleeding within 6 months prior to the first study treatment;
- Current or recent (within 10 days prior to study treatment start) ongoing treatment with full-dose anticoagulants for therapeutic purposes.
- Chronic, daily treatment with high-dose aspirin (>325 mg/day);
- Treatment with any investigational drug within 30 days prior to enrollment or 2 investigational agent half-lives (whichever is longer);
- Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of localized basal and squamous cell carcinoma or cervical cancer in situ;
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start, or anticipation of the need for major surgical procedure during the course of the study;
- Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to initiation of study treatment;
- Lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome, or inability to take oral medication;
- Pregnant or lactating women. Women of childbearing potential with either a positive or no pregnancy test at baseline. Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential. Sexually active males and females (of childbearing potential) unwilling to practice contraception (barrier contraceptive measure or oral contraception) during the study and until 6 months after the last dose of bevacizumab, fluorouracil and within 5 months after the last dose of atezolizumab;
- History of autoimmune disease;
- History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan;
- Positive test for human immunodeficiency virus (HIV);
- Active hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg] test prior to randomization) or hepatitis C;
- Active tuberculosis;
- Prior allogenic bone marrow transplantation or solid organ transplant;
- Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumour necrosis factor [TNF] agents) within 2 weeks prior to start of study treatment, or requirement for systemic immunosuppressive medications during the trial. The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) is allowed;
- Known hypersensitivity or allergy to Chinese hamster ovary cell products or any component of the atezolizumab formulation;
- Administration of a live, attenuated vaccine within 4 weeks prior to start of study treatment or anticipation that such a live attenuated vaccine will be required during the study;
- Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin-2) within 4 weeks or five half-lives of the drug, whichever is longer, prior to start of study treatment; • If receiving a RANKL inhibitor (e.g. denosumab), unwilling to adopt alternative treatment such as (but not limited to) bisphosphonates, while receiving atezolizumab.
Trial locations and contacts
24 sites in 1 country. Contact the study team or a site near you to ask about taking part.
24 sites in 1 country
Italy24 sites, 24 recruiting
- Recruiting
IRCCS Centro di Riferimento Oncologico
Aviano, PN, 33081
Elena Ongaro, elena.ongaro@cro.it
- Recruiting
Fondazione Poliambulanza, Istituto Ospedaliero
Brescia, BS, 25124
Alberto Zaniboni, MD, alberto.zaniboni@poliambulanza.it
- Recruiting
Azienda Ospedaliero Universitaria Policlinico Rodolico - S. Marco
Catania, CT, 95123
Laura Noto, DM, lauranoto1983@hotmail.it
- Recruiting
AOU Careggi
Florence, FI, 50134
Lorenzo Antonuzzo, MD, lorenzo.antonuzzo@unifi.it
- Recruiting
Azienda USL Toscana Nord Ovest
Livorno, LI, 57124
Samanta Cupini, MD, samanta.cupini@uslnordovest.toscana.it
- Recruiting
Ospedale San Luca
Lucca, LU, 55100
Editta Baldini, MD, editta.baldini@uslnordovest.toscana.it
- Recruiting
Istituto Romagnolo per lo Studio dei Tumori Dino Amadori
Meldola, FC, 47014
Alessandro Passardi, MD, alessandro.passardi@irst.emr.it
- Recruiting
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Milan, MI, 20122
Michele Ghidini, MD, michele.ghidini@policlinico.mi.it
- Recruiting
Ospedale San Raffaele
Milan, MI, 20132
Monica Ronzoni, MD, ronzoni.monica@hsr.it
- Recruiting
Fondazione IRCCS INT - Milano
Milan, MI, 20133
Filippo Pietrantonio, MD, Filippo.Pietrantonio@istitutotumori.mi.it
- Recruiting
Azienda Ospedaliero Universitaria di Modena
Modena, MO, 41124
Fabio Gelsomino, MD, gelsomino.fabio@aou.mo.it
- Recruiting
Azienda Ospedaliera Universitaria Luigi Vanvitelli
Naples, 80131
Erika Martinelli, MD, erika.martinelli@unicampania.it
- Recruiting
IRCCS Istituto Nazionale Tumori "Fondazione Giovanni Pascale"
Naples, 80131
Antonio Avallone, MD
a.avallone@istitutotumori.na.it
- Recruiting
Istituto Oncologico Veneto Irccs
Padova, PD, 35128
Sara Lonardi, MD, sara.lonardi@iov.veneto.it
- Recruiting
Azienda Usl di Piacenza
Piacenza, 29121
Margherita Ratti, MD, m.ratti2@ausl.pc.it
- Recruiting
U.O. Oncologia Medica 2 Universitaria - Azienda Ospedaliero-Universitaria Pisana Dipartimento di Ricerca Traslazionale e Nuove Tecnologie - University of Pisa
Pisa, 56126
Carlotta Antoniotti, MD, PhD, +39050992192, carlottantoniotti@gmail.com
- Recruiting
Nuovo Ospedale di Prato S. Stefano
Prato, PO, 59100
Samantha Di Donato, MD, samantha.didonato@uslcentro.toscana.it
- Recruiting
Azienda USL della Romagna
Ravenna, RA, 48121
Stefano Tamberi, MD, stefano.tamberi@auslromagna.it
- Recruiting
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Roma, RM, 00168
Lisa Salvatore, MD, lisa.salvatore@policlinicogemelli.it
- Recruiting
Policlinico Universitario Tor Vergata
Rome, 00133
Vincenzo Formica, MD, v.formica1@gmail.it
- Recruiting
Fondazione Casa Sollievo della Sofferenza
San Giovanni Rotondo, FG, 71013
Tiziana Pia Latiano, MD, t.latiano@operapadrepio.it
- Recruiting
Azienda Ospedaliera Card. G. Panico
Tricase, LE, 73039
Emiliano Tamburini, MD, emilianotamburini@icloud.com
- Recruiting
Azienda Sanitaria Universitaria Friuli Centrale
Udine, UD, 33100
Nicoletta Pella, MD, nicoletta.pella@asufc.sanita.fvg.it
- Recruiting
ASL di Viterbo
Viterbo, VT, 01100
Marta Schirripa, MD, marta.schirripa@asl.vt.it
About this study
Official title: Phase III Randomized Study of FOLFOXIRI Plus Bevacizumab and Atezolizumab Versus FOLFOXIRI Plus Bevacizumab as First-Line Treatment of Unresectable pMMR and Immunoscore IC-High Metastatic Colorectal Cancer Patients
The aim of this study is to evaluate the efficacy of the addition of Atezolizumab to FOLFOXIRI plus bevacizumab as first line treatment of patients with pMMR and Immunoscore IC-high metastatic colorectal cancer in terms of Progression Free Survival (PFS).
Read the detailed description
This is a prospective, open-label, multicenter phase III randomized trial in which patients with initially unresectable, previously untreated pMMR and Immunoscore IC-high mCRC will be randomized in a 1:1 ratio to receive induction treatment with FOLFOXIRI plus bevacizumab up to 8 cycles followed by maintenance with 5-FU/LV plus bevacizumab until disease progression, unacceptable toxicity or patient's refusal (arm A) or FOLFOXIRI plus bevacizumab plus atezolizumab up to 8 cycles followed by maintenance with 5-FU/LV plus bevacizumab plus atezolizumab until disease progression, unacceptable toxicity or patient's refusal (arm B).
Stratification factors will be ECOG Performance Status (0 versus 1, 2), primary tumour location (right versus left/rectum) and liver metastases (yes versus no).
The second- and subsequent lines of treatment will be at investigators' choice.
- Conditions
- Colorectal Cancer
- Being tested
- Atezolizumab, Bevacizumab, Irinotecan (CPT-11), Oxaliplatin, Leucovorin
- Keywords
- atezolizumab, FOLFIXIRI/bevacizumab, metastatic colorectal cancer, pMMR/MSS, IMMUSCORE IC-High, first line
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AtezolizumabDrug
840 mg iv over 30 minutes (60 minutes at first infusion) day 1
BevacizumabDrug
5 mg/kg iv over 90 minutes at cycle 1 (if well tolerated, it is administered over 60 minutes at cycle 2, and over 30 minutes at cycle 3) day 1
Irinotecan (CPT-11)Drug
165 mg/sqm iv over 60 minutes day 1
OxaliplatinDrug
85 mg/sqm iv over 2 hours day 1
LeucovorinDrug
200 mg/sqm iv over 2 hours day 1
Fluorouracil (5-FU)Drug
3200 mg/sqm 48 h-continuous infusion, starting on day 1
| Study group | Role | What they receive |
|---|---|---|
| Arm A - FOLFOXIRI plus bevacizumab | Active comparator | Every 2 weeks for a maximum of 8 cycles:
* Bevacizumab 5 mg/kg iv 90 minutes at cycle 1 (if well tolerated, it is administered over 60 minutes at cycle 2, and over 30 minutes at cycle 3) day 1, followed by
* Irinotecan 165 mg/sqm iv over 60 minutes day 1, followed by
* Oxaliplatin 85 mg/sqm iv over 2 hours day 1, in two-way with
* L-Leucovorin 200 mg/sqm iv over 2 hours day 1, followed by
* 5-fluorouracil 3200 mg/sqm 48 h-continuous infusion, starting on day 1.
If no progression occurs during FOLFOXIRI plus bev, patients will receive maintenance 5-FU/LV plus bev at the same dose used at the last cycle of the induction treatment. 5-FU/LV plus bev will be repeated biweekly until disease progression, unacceptable toxicity or patient's refusal. Receives: Drug: Bevacizumab; Drug: Irinotecan (CPT-11); Drug: Oxaliplatin; Drug: Leucovorin; Drug: Fluorouracil (5-FU) |
| Arm B - FOLFOXIRI plus bevacizumab plus atezolizumab | Experimental | Every 2 weeks for a maximum of 8 cycles:
* Atezolizumab 840 mg iv over 30 minutes (60 minutes at first infusion) day 1 followed by
* Bevacizumab 5 mg/kg iv over 90 minutes at cycle 1 (if well tolerated, it is administered over 60 minutes at cycle 2, and over 30 minutes at cycle 3) day 1 followed by
* Irinotecan 165 mg/sqm iv over 60 minutes day 1, followed by
* Oxaliplatin 85 mg/sqm iv over 2 hours day 1, in two-way with
* L-Leucovorin 200 mg/sqm iv over 2 hours day 1, followed by
* 5-fluorouracil 3200 mg/sqm 48 h-continuous infusion, starting on day 1.
If no progression occurs during FOLFOXIRI plus bev plus atezolizumab, patients will receive maintenance 5-FU/LV plus bev plus atezolizumab at the same dose used at the last cycle of the induction treatment. 5-FU/LV plus bev plus atezolizumab will be repeated biweekly until disease progression, unacceptable toxicity or patient's refusal. Receives: Drug: Atezolizumab; Drug: Bevacizumab; Drug: Irinotecan (CPT-11); Drug: Oxaliplatin; Drug: Leucovorin; Drug: Fluorouracil (5-FU) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival (PFS)
PFS is defined as the time from randomization to the first documentation of objective disease progression or death due to any cause, whichever occurs first. PFS will be censored on the date of the last evaluable on study tumor assessment documenting absence of progressive disease for patients who are alive, on study and progression free at the time of the analysis. Alive patients having no tumor assessments after baseline will have time to event censored on the date of randomization.
Measured: 24 months
Secondary outcomes (12)
Overall Toxicity Rate
Overall Toxicity Rate is defined as the percentage of patients, relative to the total of enrolled subjects, experiencing any adverse event, according to National Cancer Institute Common Toxicity Criteria (version 5.0), during the induction and the maintenance phases of treatment.
Measured: 24 months
Toxicity Rate
Toxicity Rate is defined as the percentage of patients, relative to the total of enrolled subjects, experiencing a specific adverse event of grade 3/4, according to National Cancer Institute Common Toxicity Criteria (version 5.0), during the induction and the maintenance phases of treatment.
Measured: 24 months
Objective Response Rate
Objective Response Rate (ORR) is defined as the percentage of patients, relative to the total of enrolled subjects, achieving a complete (CR) or partial (PR) response, according to RECIST 1.1 criteria, during the induction and the maintenance phases of treatment. The determination of clinical response will be based on investigator reported measurements. Responses will be evaluated every 8 weeks.
Measured: 24 months
Immuno-related Objective Response Rate
Immuno-related Objective Response Rate (irORR) is defined as the percentage of patients, relative to the total of enrolled subjects, achieving a complete (CR) or partial (PR) response, according to immune-modified RECIST criteria, during the induction and the maintenance phases of treatment. The determination of clinical response will be based on investigator reported measurements. Responses will be evaluated every 8 weeks.
Measured: 24 months
Early Objective Response Rate
Early Objective Response Rate (EOR) is defined as the percentage of patients, relative to the total of the enrolled subjects, achieving a ≥20% decrease in the sum of diameters of RECIST target lesions at week 8 compared to baseline.
Measured: up to 2 months from randomization
Depth of Response
Depth of Response (DpR) is defined as the relative change in the sum of longest diameters of RECIST target lesions at the nadir, in the absence of new lesions or progression of non-target lesions, when compared with baseline.
Measured: 24 months
R0 Resection Rate
R0 Resection Rate is defined as the percentage of patients, relative to the total of enrolled subjects, undergoing secondary R0 resection of metastases. Secondary R0 surgery is defined as microscopically margin free complete surgical removal of all residual disease, performed during treatment or after its completion, allowed by tumoral shrinkage and/or disappearance of one or more lesions.
Measured: 24 months
Duration of Response
Duration of Response (DoR) is defined as the time from first documentation of objective response (complete [CR] or partial [PR] response, per RECIST 1.11) to the first documentation of PD (per RECIST 1.1) or to death to any cause, whichever comes first.
Measured: 24 months
Overall survival
Overall survival (OS) is defined as the time from randomization to the date of death due to any cause. For patients still alive at the time of analysis, the OS time will be censored on the last date the patients were known to be alive.
Measured: 48 months
Quality of Life as assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)
The EORTC QLQ-C30 contains functional scales, symptom scales, single items scale and a global health status/QoL scale. Raw scores are standardized and converted into scale scores ranging from 0 to 100. Higher scores represent better functioning on the functional scales and a higher level of symptoms on the symptom scales. Quality of life will be evaluated for patients who will have completed at least one questionnaire item at baseline and during the study period through descriptive summary statistics.
Measured: Questionnaires will be administered at baseline, every 4 weeks during induction treatment, every 8 weeks thereafter, at the time of evidence of disease progression, after 30 days following end of study treatment/disease progression.
Quality of Life as assessed by the European Organization for Research and Treatment of Cancer Quality of Life Module for Colorectal cancer 29 (EORTC QLQ-CR29).
The EORTC QLQ-CR29 includes 29 items that evaluate symptoms (gastrointestinal, urinary, pain and others) and functional areas (sexual, body image and others) that are associated with CRC and its treatments. There are separate items for patients with and without a stoma and separate items to evaluate the sexual function of men and women. Raw scores are standardized and converted into scale scores ranging from 0 to 100. Higher scores represent better functioning on the functional scales and a higher level of symptoms on the symptom scales. Quality of life will be evaluated for patients who will have completed at least one questionnaire item at baseline and during the study period through descriptive summary statistics.
Measured: Questionnaires will be administered at baseline, every 4 weeks during induction treatment, every 8 weeks thereafter, at the time of evidence of disease progression, after 30 days following end of study treatment/disease progression.
Time To Deterioration in Quality of Life (TTD)
The time from baseline to the first onset of a 10-point or greater decrease from baseline for functional scales or a 10-point or greater increase for symptom scales or death.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Dec 2024
- Study start15 Nov 2024
- Primary completion1 Apr 2028 (estimated)
- Study completion1 Apr 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CancerStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 238 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Gruppo Oncologico del Nord-Ovest
- Sponsor type
- University, hospital or other
- Collaborators
- Hoffmann-La Roche
- Responsible party
- Sponsor
- Investigators
- Carlotta Antoniotti, MD, PhD, Principal investigator, Department of Translational Research and New Technologies in Medicine and Surgery - University of Pisa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06733038
- Sponsor's protocol ID
- AtezoTRIBE2
- Acronym
- AtezoTRIBE2
- Status last verified
- Dec 2025
- First submitted
- 2 Dec 2024
- Last updated
- 8 Dec 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase III Randomized Study of FOLFOXIRI Plus Bevacizumab and Atezolizumab Versus FOLFOXIRI Plus Bevacizumab as First-Line Treatment of Unresectable pMMR and Immunoscore IC-High Metastatic Colorectal Cancer Patients
- ClinicalTrials.gov ID
- NCT06733038
- Acronym / sponsor ID
- AtezoTRIBE2 / AtezoTRIBE2
- Conditions
- Colorectal Cancer
- Keywords
- atezolizumab, FOLFIXIRI/bevacizumab, metastatic colorectal cancer, pMMR/MSS, IMMUSCORE IC-High, first line
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 238 participants (estimated)
- Lead sponsor
- Gruppo Oncologico del Nord-OvestUniversity, hospital or other
- Collaborators
- Hoffmann-La Roche
- Study start
- 15 Nov 2024 (actual)
- Primary completion
- 1 Apr 2028 (estimated)
- Study completion
- 1 Apr 2029 (estimated)
- First posted
- 13 Dec 2024 (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.
The aim of this study is to evaluate the efficacy of the addition of Atezolizumab to FOLFOXIRI plus bevacizumab as first line treatment of patients with pMMR and Immunoscore IC-high metastatic colorectal cancer in terms of Progression Free Survival (PFS).
Detailed description
This is a prospective, open-label, multicenter phase III randomized trial in which patients with initially unresectable, previously untreated pMMR and Immunoscore IC-high mCRC will be randomized in a 1:1 ratio to receive induction treatment with FOLFOXIRI plus bevacizumab up to 8 cycles followed by maintenance with 5-FU/LV plus bevacizumab until disease progression, unacceptable toxicity or patient's refusal (arm A) or FOLFOXIRI plus bevacizumab plus atezolizumab up to 8 cycles followed by maintenance with 5-FU/LV plus bevacizumab plus atezolizumab until disease progression, unacceptable toxicity or patient's refusal (arm B).
Stratification factors will be ECOG Performance Status (0 versus 1, 2), primary tumour location (right versus left/rectum) and liver metastases (yes versus no).
The second- and subsequent lines of treatment will be at investigators' choice.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A - FOLFOXIRI plus bevacizumab | Active comparator | Drug: Bevacizumab, Drug: Irinotecan (CPT-11), Drug: Oxaliplatin, Drug: Leucovorin, Drug: Fluorouracil (5-FU)Every 2 weeks for a maximum of 8 cycles: * Bevacizumab 5 mg/kg iv 90 minutes at cycle 1 (if well tolerated, it is administered over 60 minutes at cycle 2, and over 30 minutes at cycle 3) day 1, followed by * Irinotecan 165 mg/sqm iv over 60 minutes day 1, followed by * Oxaliplatin 85 mg/sqm iv over 2 hours day 1, in two-way with * L-Leucovorin 200 mg/sqm iv over 2 hours day 1, followed by * 5-fluorouracil 3200 mg/sqm 48 h-continuous infusion, starting on day 1. If no progression occurs during FOLFOXIRI plus bev, patients will receive maintenance 5-FU/LV plus bev at the same dose used at the last cycle of the induction treatment. 5-FU/LV plus bev will be repeated biweekly until disease progression, unacceptable toxicity or patient's refusal. |
| Arm B - FOLFOXIRI plus bevacizumab plus atezolizumab | Experimental | Drug: Atezolizumab, Drug: Bevacizumab, Drug: Irinotecan (CPT-11), Drug: Oxaliplatin, Drug: Leucovorin, Drug: Fluorouracil (5-FU)Every 2 weeks for a maximum of 8 cycles: * Atezolizumab 840 mg iv over 30 minutes (60 minutes at first infusion) day 1 followed by * Bevacizumab 5 mg/kg iv over 90 minutes at cycle 1 (if well tolerated, it is administered over 60 minutes at cycle 2, and over 30 minutes at cycle 3) day 1 followed by * Irinotecan 165 mg/sqm iv over 60 minutes day 1, followed by * Oxaliplatin 85 mg/sqm iv over 2 hours day 1, in two-way with * L-Leucovorin 200 mg/sqm iv over 2 hours day 1, followed by * 5-fluorouracil 3200 mg/sqm 48 h-continuous infusion, starting on day 1. If no progression occurs during FOLFOXIRI plus bev plus atezolizumab, patients will receive maintenance 5-FU/LV plus bev plus atezolizumab at the same dose used at the last cycle of the induction treatment. 5-FU/LV plus bev plus atezolizumab will be repeated biweekly until disease progression, unacceptable toxicity or patient's refusal. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Histologically proven diagnosis of colorectal cancer;
- Initially unresectable metastatic colorectal cancer not previously treated with chemotherapy for metastatic disease;
- Proficient mismatch repair (pMMR) status in tumour tissue (primary or metastatic), as determined by a local laboratory assay in a CLIA- or similarly certified;
- Immunoscore IC-high status in tumour tissue (primary or metastatic), as determined by a sponsor-defined central laboratory (HEGP, AP-HP, INSERM, France).
- At least one measurable lesion according to RECIST criteria (version 1.1);
Key exclusion criteria (36 listed)
- Radiotherapy to any site within 4 weeks before the study;
- Previous adjuvant oxaliplatin-containing chemotherapy;
- Previous treatment with bevacizumab;
- Prior treatment with CD137 agonists, anti-CTLA4, anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents;
- Complete dihydropyrimidine dehydrogenase (DPYD) deficiency (homozygous of the following DPYD polymorphisms: c1679GG, c1905+1AA, c2846TT);
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 |
|---|---|---|
| Atezolizumab840 mg iv over 30 minutes (60 minutes at first infusion) day 1 | Drug | Arm B - FOLFOXIRI plus bevacizumab plus atezolizumab |
| Bevacizumab5 mg/kg iv over 90 minutes at cycle 1 (if well tolerated, it is administered over 60 minutes at cycle 2, and over 30 minutes at cycle 3) day 1 | Drug | Arm A - FOLFOXIRI plus bevacizumab, Arm B - FOLFOXIRI plus bevacizumab plus atezolizumab |
| Irinotecan (CPT-11)165 mg/sqm iv over 60 minutes day 1 | Drug | Arm A - FOLFOXIRI plus bevacizumab, Arm B - FOLFOXIRI plus bevacizumab plus atezolizumab |
| Oxaliplatin85 mg/sqm iv over 2 hours day 1 | Drug | Arm A - FOLFOXIRI plus bevacizumab, Arm B - FOLFOXIRI plus bevacizumab plus atezolizumab |
| Leucovorin200 mg/sqm iv over 2 hours day 1 | Drug | Arm A - FOLFOXIRI plus bevacizumab, Arm B - FOLFOXIRI plus bevacizumab plus atezolizumab |
| Fluorouracil (5-FU)3200 mg/sqm 48 h-continuous infusion, starting on day 1 | Drug | Arm A - FOLFOXIRI plus bevacizumab, Arm B - FOLFOXIRI plus bevacizumab plus atezolizumab |
Primary outcome
Progression Free Survival (PFS)
Time frame: 24 months
PFS is defined as the time from randomization to the first documentation of objective disease progression or death due to any cause, whichever occurs first. PFS will be censored on the date of the last evaluable on study tumor assessment documenting absence of progressive disease for patients who are alive, on study and progression free at the time of the analysis. Alive patients having no tumor assessments after baseline will have time to event censored on the date of randomization.
12 secondary outcomes
Overall Toxicity Rate
Time frame: 24 months
Toxicity Rate
Time frame: 24 months
Objective Response Rate
Time frame: 24 months
Immuno-related Objective Response Rate
Time frame: 24 months
Early Objective Response Rate
Time frame: up to 2 months from randomization
Depth of Response
Time frame: 24 months
R0 Resection Rate
Time frame: 24 months
Duration of Response
Time frame: 24 months
Overall survival
Time frame: 48 months
Quality of Life as assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)
Time frame: Questionnaires will be administered at baseline, every 4 weeks during induction treatment, every 8 weeks thereafter, at the time of evidence of disease progression, after 30 days following end of study treatment/disease progression.
Quality of Life as assessed by the European Organization for Research and Treatment of Cancer Quality of Life Module for Colorectal cancer 29 (EORTC QLQ-CR29).
Time frame: Questionnaires will be administered at baseline, every 4 weeks during induction treatment, every 8 weeks thereafter, at the time of evidence of disease progression, after 30 days following end of study treatment/disease progression.
Time To Deterioration in Quality of Life (TTD)
Time frame: 24 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 8 Dec 2025.
- Individual participant dataSharing planned: No
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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.
Carlotta Antoniotti, MD, PhD principal investigator
Department of Translational Research and New Technologies in Medicine and Surgery - University of Pisa
24 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Atezolizumab, Bevacizumab and Irinotecan (CPT-11) in people with Colorectal Cancer, run by Gruppo Oncologico del Nord-Ovest at 24 sites in Italy.
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 20 inclusion and 36 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 8 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in Italy. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 Carlotta Antoniotti, MD, PhD (+39050992192, carlotta.antoniotti@unipi.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression Free Survival (PFS) (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 8 Dec 2025.