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Bevacizumab

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Cetuximab

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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.

folfoxiri+cetuximab+surgery+cetuximab

folfoxiri+cetuximab+surgery+bevacizumab

Alfredo Falcone, MD

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.

Induction Chemoterapy With Folfoxiri Plus Cetuxumab in Unresectable Colorectal Cancer Patient

Induction Chemotherapy With Folfoxiri Plus Cetuximab and Maintenance With Cetuximab or Bevacizumab Therapy in Unresectable Kras Wild-type Metastatic Colorectal Cancer Patients

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.

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.

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.

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.

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

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

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.

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.

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Induction Chemoterapy With Folfoxiri Plus Cetuxumab in Unresectable Colorectal Cancer Patient	NCT02295930	Metastatic Colo...	folfoxiri+cetux... folfoxiri+cetux...	18 Years - 75 Years	Gruppo Oncologico del Nord-Ovest
Induction Chemoterapy With Folfoxiri Plus Cetuxumab in Unresectable Colorectal Cancer Patient	NCT02295930	Metastatic Colo...	folfoxiri+cetux... folfoxiri+cetux...	18 Years - 75 Years	Gruppo Oncologico del Nord-Ovest

Spots Global Cancer Trial Database for folfoxiri+cetuximab+surgery+bevacizumab