This study consist of 4-months induction first-line chemotherapy with the G.O.N.O. FOLFOXIRI regimen plus bevacizumab followed by maintenance with bevacizumab or bevacizumab plus metronomic chemotherapy (with capecitabine and cyclophosphamide) in mCRC patients. The main objective of this study is to preliminarily evaluate the potential effects of the combination of a metronomic chemotherapy with capecitabine and cyclophosphamide to maintenance bevacizumab on pharmacodynamic and clinical parameters among mCRC patients.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
232
Patients will be randomly assigned to receive induction chemotherapy with the G.O.N.O. FOLFOXIRI regimen plus bevacizumab: * BEVACIZUMAB 5 mg/kg over 30 minutes, day 1 * IRINOTECAN 165 mg/sqm IV over 1-h, day 1 * OXALIPLATIN 85 mg/sqm IV over 2-h, day 1 * L-LEUCOVORIN 200 mg/sqm IV over 2-h, day 1 * 5-FLUOROURACIL 3200 mg/sqm IV 48-h continuous infusion, starting on day 1 with cycles repeated every 2 weeks for 4 months (8 cycles), followed after 2 weeks by (if no progression occurs): \- BEVACIZUMAB 7.5 mg/kg over 30 minutes, day 1 (every three weeks)
Patients will be randomly assigned to receive induction chemotherapy with the G.O.N.O. FOLFOXIRI regimen plus bevacizumab: * BEVACIZUMAB 5 mg/kg over 30 minutes, day 1 * IRINOTECAN 165 mg/sqm IV over 1-h, day 1 * OXALIPLATIN 85 mg/sqm IV over 2-h, day 1 * L-LEUCOVORIN 200 mg/sqm IV over 2-h, day 1 * 5-FLUOROURACIL 3200 mg/sqm IV 48-h continuous infusion, starting on day 1 with cycles repeated every 2 weeks for 4 months (8 cycles), followed after 2 weeks by (if no progression occurs): * BEVACIZUMAB 7.5 mg/kg over 30 minutes, day 1 (every three weeks), * CAPECITABINE 500 mg/tid orally, continuously, * CYCLOPHOSPHAMIDE 50 mg/day orally, continuously.
Istituto Ospedaliero Fondazione Poliambulanza Di Brescia
Brescia, Italy
Pres.Ospedaliero Spedali Civili Brescia
Brescia, Italy
Istituti Ospitalieri Di Cremona
Cremona, Italy
Azienda Ospedaliera S. Croce E Carle Di Cuneo
Cuneo, Italy
A.O. Universitaria Arcispedale S.Anna Di Ferrara
Ferrara, Italy
Ausl Di Frosinone -
Frosinone, Italy
E.O. Ospedali Galliera
Genova, Italy
Ospedale Per Acuti Mater Salutis Di Legnago
Legnago, Italy
Oncologia AUSL 2 Lucca
Lucca, Italy
Irccs Fondazione Centro S. Raffaele Del Monte Tabor
Milan, Italy
...and 10 more locations
progression-free survival (PFS)
PFS is defined as the time from randomization to 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 endpoint censored on the date of randomization.Disease status will be evaluated according to RECIST 1.1 criteria.
Time frame: up to 4 years
Best overall response rate (ORR)
It is defined as the percentage of patients,relative to the total of enrolled subjects,achieving a complete or partial 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.Patients who do not have an on-study assessment will be included in the analysis as non responders.
Time frame: up to 4 years
Duration of response
it is defined as the time from the date when measurement criteria are met for CR or PR until first documentation of objective disease progression
Time frame: up to 4 years
Resection rate
it is defined as the percentage of patients, relative to the total of enrolled subjects, undergoing secondary R0 resection of metastases during treatment or after its completion. Secondary R0 surgery is defined as microscopically margin-free complete surgical removal of all residual disease, allowed by tumoral shrinkage and/or disappearance of one or more lesions.
Time frame: up to 4 years
Time to strategy failure (TSF)
it is defined as the time from the day of randomization to one of the followings: 1. progression during FOLFOXIRI + bevacizumab or during a modified FOLFOXIRI + bevacizumab regimen; OR 2. progression and decision to not administer FOLFOXIRI + bevacizumab or a modified FOLFOXIRI + bevacizumab regimen; OR 3. introduction of a new agent not included in the study treatment according to randomization arm; OR 4. death; whichever occurs first.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.
Time frame: up to 4 years
Time to 2nd progressive disease
it is defined as the time from randomization to second documentation of objective disease progression or death due to any cause, whichever occurs first. 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: up to 4 years
Overall survival (OS)
it 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.
Time frame: up to 4 years
Toxicity rate
it is defined as the percentage of patients, relative to the total of enrolled subjects, experiencing a specific adverse event, according to National Cancer Institute Common Toxicity Criteria (version 4.0), during the induction and the maintenance phases of treatment.
Time frame: up to 4 years
Overall toxicity rate
it 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 4.0), during the induction and the maintenance phases of treatment.
Time frame: up to 4 years
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