This is a phase II randomized study of 4-months induction first-line chemotherapy with FOLFOXIRI + cetuximab followed by maintenance with cetuximab or bevacizumab in patients affected by KRAS wild type (wt) mCRC.
The aim of the study is to obtain a rapid disease control with the therapy and the maximum tumoral shrinkage, and than to treat patient with less intensive maintenance to inhibit tumoral regrowth.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
143
Induction FOLFOXIRI plus cetuximab will consist of: * CETUXIMAB 500 mg/sqm IV over 1-h\* , day 1 followed by * IRINOTECAN 130 mg/sqm IV over 1-h, day 1 followed by * OXALIPLATIN 85 mg/sqm IV over 2-h, day 1 concomitantly with * l-LV 200 mg/sqm IV over 2-h, day 1 followed by * 5-FLUOROURACIL 2400 mg/sqm IV 48-h continuous infusion, starting on day 1 repeated every 2 weeks for 8 cycles. Surgical revaluation will be performed after the induction phase (8 cycles). Patients deemed unsuitable for surgery will received maintenance treatment as follows: •CETUXIMAB 500 mg/sqm IV over 60-min, day 1 repeated every 2 weeks until PD, patient's refusal, unacceptable toxicity or consent withdrawal.
Induction FOLFOXIRI plus cetuximab will consist of: * CETUXIMAB 500 mg/sqm IV over 1-h\* , day 1 followed by * IRINOTECAN 130 mg/sqm IV over 1-h, day 1 followed by * OXALIPLATIN 85 mg/sqm IV over 2-h, day 1 concomitantly with * l-LV 200 mg/sqm IV over 2-h, day 1 followed by * 5-FLUOROURACIL 2400 mg/sqm IV 48-h continuous infusion, starting on day 1 repeated every 2 weeks for 8 cycles. Surgical revaluation will be performed after the induction phase (8 cycles). Patients deemed unsuitable for surgery will received maintenance treatment as follows: •BEVACIZUMAB 5 mg/kg IV over 30-min, day 1 repeated every 2 weeks until PD, patient's refusal, unacceptable toxicity or consent withdrawal.
10 months-progression free rate (10m-PFR)
10m-PFR is defined as the proportion of patients free from disease progression 10 months after randomization, relative to the total of enrolled patients. Patients whose disease status cannot be evaluated within 11 months after randomization and patients lost to follow up or dead within 10 months after randomization will be considered as progressed for the purpose of the primary endpoint analyses.
Time frame: up to 10 months
Best overall response rate
Best overall response rate 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 that will be subsequently confirmed by a central review. Responses will be evaluated every 8 weeks until disease progression or up to 60 months. Patients who do not have an on-study assessment will be included in the analysis as non responders.
Time frame: every 8 weeks, up to 60 months
10 month resection rate
10month resection rate is defined as the percentage of patients,relative to the total of enrolled subjects,undergoing secondary R0 resection of metastases within 10months after randomization.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 1or more lesions.Patients lost to follow up,with disease progression or dead,within 10months after randomization,will be considered as failures.
Time frame: within 10 months after randomization
Time to strategy failure
It is defined as the time from randomization to one of the followings: 1. progression during FOLFOXIRI + cetuximab or during a modified FOLFOXIRI + cetuximab regimen;OR 2. progression and decision to not administer FOLFOXIRI + cetuximab or a modified FOLFOXIRI + cetuximab regimen 3. introduction of a new agent not included in the study treatment according to randomization arm;OR 4. death; whichever occurs first.All events will be assessed up to 60 months.For patients still on treatment at the time of analysis, the time to strategy failure will be censored on the last date the patients were known to be alive.
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A.O.Universitaria Policlinico S.Orsola-Malpighi Di Bologna (Oncologia Medica)
Bologna, Italy, Italy
AUSL DI FROSINONE - FROSINONE (FR) ONCOLOGIA MEDICA U.O. Oncologia Medica
Frosinone, Italy, Italy
Ausl 12 Di Viareggio (Lu) - Lido Di Camaiore (Lu) Oncologia Medica
Lucca, Italy, Italy
AZIENDA OSPEDALIERA DI PERUGIA - OSPEDALE S. MARIA DELLA MISERICORDIA - PERUGIA (PG) ONCOLOGIA MEDICA U.O. Oncologia Medica
Perugia, Italy, Italy
Polo Oncologico Area Vasta Nord Ovest
Pisa, Italy, Italy
Ospedale Civile Ss. Antonio E Biagio Di Alessandria - Alessandria (Al) Oncologia Medica
Alessandria, Italy
Irccs Centro Di Riferimento Oncologico (Cro) - Aviano (Pn)
Aviano, Italy
Istituto Ospedaliero Fondazione Poliambulanza Di Brescia - Brescia (Bs) Oncologia Medica
Brescia, Italy
Pres.Ospedal.Spedali Civili Brescia - Brescia (Bs) Oncologia Medic
Brescia, Italy
Ospedale Armando Businco - Cagliari (Ca) Oncologia Medica
Cagliari, Italy
...and 12 more locations
Time frame: from randomization, up to 60 months
Time to 2nd progressive disease
It is defined as the time from randomization to 2°documentation of objective disease progression or death due to any cause,whichever occurs first.All events will be assessed up to 60 months.Time to 2nd progressive disease 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 second progression free at the time of the analysis.Alive patients having no tumor assessments after baseline will have time to event endpoint censored on the date of randomization
Time frame: from randomization, up to 60 months
Progression free survival (PFS)
It is defined as the time from randomization to first documentation of objective disease progression or death due to any cause,whichever occurs first. All events will be assessed up to 60 months. 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 endpoint censored on the date of randomization
Time frame: from randomization to first documentation of objective disease progression or death, up to 60 months
Overall survival (OS)
It is defined as the time from randomization to the date of death due to any cause. All events will be assessed up to 60 months. 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.
Time frame: as the time from randomization to the date of death, up to 60 months
Toxicity rate
It 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 4.0),during the induction and the maintenance phases of treatment.
Time frame: during the induction and the maintenance phases of treatment
Overall toxicity rate
It is defined as the percentage of patients, relative to the total of enrolled subjects, experiencing any adverse event of grade 3/4, according to National Cancer Institute Common Toxicity Criteria (version 4.0), during the induction and the maintenance phases of treatment.
Time frame: during the induction and the maintenance phases of treatment