FOLFOXIRI Plus Bevacizumab With or Without Atezolizumab as 1st Line Treatment of pMMR and IS IC-High Metastatic Colorectal Cancer Patients.

Recruiting now · Phase 3

Conditions studied: Colorectal Cancer

In brief

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).

Key facts

Study ID

NCT06733038

Run by

Gruppo Oncologico del Nord-Ovest

People needed

238

Starts

2024-11-15

Expected to finish

2029-04-01

Last updated by the study team

2025-12-08

Who can join

Age: 18 and older, up to 75. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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);
• 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.

You may not qualify if…

• 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;
• 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;

Where it is running

• Fondazione Poliambulanza, Istituto Ospedaliero — Brescia, BS, Italy (enrolling)
• Azienda Ospedaliero Universitaria Policlinico Rodolico - S. Marco — Catania, CT, Italy (enrolling)
• Istituto Romagnolo per lo Studio dei Tumori Dino Amadori — Meldola, FC, Italy (enrolling)
• Fondazione Casa Sollievo della Sofferenza — San Giovanni Rotondo, FG, Italy (enrolling)
• AOU Careggi — Florence, FI, Italy (enrolling)
• Azienda Ospedaliera Card. G. Panico — Tricase, LE, Italy (enrolling)
• Azienda USL Toscana Nord Ovest — Livorno, LI, Italy (enrolling)
• Ospedale San Luca — Lucca, LU, Italy (enrolling)
• Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico — Milan, MI, Italy (enrolling)
• Ospedale San Raffaele — Milan, MI, Italy (enrolling)
• Fondazione IRCCS INT - Milano — Milan, MI, Italy (enrolling)
• Azienda Ospedaliero Universitaria di Modena — Modena, MO, Italy (enrolling)
• Istituto Oncologico Veneto Irccs — Padova, PD, Italy (enrolling)
• IRCCS Centro di Riferimento Oncologico — Aviano, PN, Italy (enrolling)
• Nuovo Ospedale di Prato S. Stefano — Prato, PO, Italy (enrolling)
• Azienda USL della Romagna — Ravenna, RA, Italy (enrolling)
• Fondazione Policlinico Universitario Agostino Gemelli IRCCS — Roma, RM, Italy (enrolling)
• Azienda Sanitaria Universitaria Friuli Centrale — Udine, UD, Italy (enrolling)
• ASL di Viterbo — Viterbo, VT, Italy (enrolling)
• Azienda Ospedaliera Universitaria Luigi Vanvitelli — Naples, Italy (enrolling)
• IRCCS Istituto Nazionale Tumori "Fondazione Giovanni Pascale" — Naples, Italy (enrolling)
• Azienda Usl di Piacenza — Piacenza, Italy (enrolling)
• U.O. Oncologia Medica 2 Universitaria - Azienda Ospedaliero-Universitaria Pisana Dipartimento di Ricerca Traslazionale e Nuove Tecnologie - University of Pisa — Pisa, Italy (enrolling)
• Policlinico Universitario Tor Vergata — Rome, Italy (enrolling)

Full record on ClinicalTrials.gov

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