Metastatic Colorectal CancerPhase 2MACBETHNCT02295930
Induction Chemoterapy With Folfoxiri Plus Cetuxumab in Unresectable Colorectal Cancer Patient
A Phase 2 study testing folfoxiri+cetuximab+surgery+cetuximab and folfoxiri+cetuximab+surgery+bevacizumab in people with Metastatic Colorectal Cancer, run by Gruppo Oncologico del Nord-Ovest at 22 sites in Italy.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- folfoxiri+cetuximab+surgery+cetuximab and folfoxiri+cetuximab+surgery+bevacizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 143 participants
- Where
- 22 sitesItaly
- Study dates
- Oct 2011to Mar 2015
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 confirmed colorectal adenocarcinoma;
- Availability of formalin-fixed paraffin embedded tumor block from primary and/or metastasis;
- KRAS wild-type status of primary colorectal cancer or related metastasis;
- Unresectable and measurable metastatic disease according to RECIST criteria;
- Male or female, aged > 18 years and < 75 years;
- ECOG PS < 2 if aged < 71 years, ECOG PS = 0 if aged 71-75 years;
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- Life expectancy of more than 3 months;
- Adequate haematological function: ANC ≥ 1.5 x 109/L; platelets ≥ 100 x 109/L, Hb ≥ 9 g/dL;
- Adequate liver and renal function: serum bilirubin ≤ 1.5 x ULN; alkaline phosphatase and transaminases ≤ 2.5 x ULN (in case of liver metastases < 5 x ULN); serum creatinine ≤ 1.5 x ULN;
- Previous adjuvant chemotherapy containing oxaliplatin is allowed if more than 12 months have elapsed between the end of adjuvant therapy and first relapse;
- Previous adjuvant chemotherapy with fluoropyrimidine monotherapy is allowed if more than 6 months have elapsed between the end of adjuvant and first relapse;
- At least 6 weeks from prior extended radiotherapy and 4 weeks from surgery;
- Written informed consent to experimental treatment and KRAS analysis.
Who cannot join
- Prior palliative chemotherapy;
- Prior treatment with EGFR or VEGF inhibitors;
- Symptomatic peripheral neuropathy > 2 grade NCIC-CTG criteria;
- Presence or history of CNS metastasis;
- Active uncontrolled infections; active disseminated intravascular coagulation;
- Past or current history of malignancies other than colorectal carcinoma, except for curatively treated basal and squamous cell carcinoma of the skin cancer or in situ carcinoma of the cervix;
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- Clinically significant cardiovascular disease: cerebrovascular accidents or myocardial infarction ≤ 12 months before treatment start, unstable angina, NYHA ≥ grade 2 chronic heart failure, uncontrolled arrhythmia, uncontrolled hypertension;
- Serious, non-healing wound, ulcer, or bone fracture;
- Evidence of bleeding diathesis or coagulopathy;
- Major surgical procedure or significant traumatic injury within 28 days prior to study treatment start;
- Current or recent (within 10 days prior to study treatment start) ongoing treatment with anticoagulants for therapeutic purposes or chronic, daily treatment with high-dose aspirin (>325 mg/day);
- Subtotal colectomy, malabsorption syndrome and chronic inflammatory bowel disease (i.e. ulcerative colitis, Chron syndrome);
- Fertile women (<2 years after last menstruation) and men of childbearing potential not willing to use effective means of contraception.
- Psychiatric disorder precluding understanding of information on trial related topics,
- Serious underlying medical condition (judged by the investigator) which could impair the ability of the patient to participate in the trial (e.g. uncontrolled diabetes mellitus, active autoimmune disease)
- Concurrent treatment with other experimental drugs or other anti-cancer therapy; treatment in a clinical trial within 30 days prior to trial entry
- Definite contraindications for the use of corticosteroids and antihistamines as premedication
- Known hypersensitivity to trial drugs or hypersensitivity to any other component of the trial drugs
- Any concomitant drugs contraindicated for use with the trial drugs according to the product information of the pharmaceutical companies
- Pregnancy
- Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
- Medical or psychological condition which, in the opinion of the investigator, would not permit the patient to complete the study or sign meaningful informed consent
Trial locations and contacts
22 sites in 1 country.
22 sites in 1 country
Italy22 sites
Ospedale Civile Ss. Antonio E Biagio Di Alessandria - Alessandria (Al) Oncologia Medica
Alessandria, 15100
Irccs Centro Di Riferimento Oncologico (Cro) - Aviano (Pn)
Aviano, 33081
A.O.Universitaria Policlinico S.Orsola-Malpighi Di Bologna (Oncologia Medica)
Bologna, Italy, 40138
Istituto Ospedaliero Fondazione Poliambulanza Di Brescia - Brescia (Bs) Oncologia Medica
Brescia, 25124
Pres.Ospedal.Spedali Civili Brescia - Brescia (Bs) Oncologia Medic
Brescia, 25125
Ospedale Armando Businco - Cagliari (Ca) Oncologia Medica
Cagliari, 09121
Azienza Ospedaliera S. Croce E Carle
Cuneo, 12100
AUSL DI FROSINONE - FROSINONE (FR) ONCOLOGIA MEDICA U.O. Oncologia Medica
Frosinone, Italy, 03100
IRCCS ISTITUTO NAZIONALE PER LA RICERCA SUL CANCRO (IST) - GENOVA (GE) ONCOLOGIA MEDICA Oncologia Medica A
Genova, 16132
Ausl 12 Di Viareggio (Lu) - Lido Di Camaiore (Lu) Oncologia Medica
Lucca, Italy, 50053
Irccs Istituto Oncologico Veneto (Iov) - Padova (Pd) Oncologia Medica
Padova, 35128
AZIENDA OSPEDALIERA DI PERUGIA - OSPEDALE S. MARIA DELLA MISERICORDIA - PERUGIA (PG) ONCOLOGIA MEDICA U.O. Oncologia Medica
Perugia, Italy, 06156
Polo Oncologico Area Vasta Nord Ovest
Pisa, Italy, 56100
AUSL 5 DI PISA - PISA (PI) ONCOLOGIA MEDICA oncologia medica Osp Lotti Pontedera
Pontedera, 56100
Ospedale Di S. Maria Nuova - Reggio Nell'Emilia (Re) Oncologia Medica
Reggio Emilia, 42100
Policlinico Universitario Campus Bio-Medico Di Roma - Roma (Rm) Oncologia Medica
Roma, 00128
POLICLINICO UMBERTO I DI ROMA - ROMA (RM) ONCOLOGIA MEDICA oncologia Medica
Roma, 00161
Ospedale Fatebenefratelli
Roma, 00186
Ospedale San Pietro Fatebenefratelli - Roma (Rm) Oncologia Medica
Roma, 00189
Ospedale Civile Di Sondrio
Sondrio, 23100
A.O. Universitaria S. Giovanni Battista-Molinette Di Torino - Torino (to) Oncologia Medica
Torino, 10134
A.O. UNIVERSITARIA S. MARIA DELLA MISERICORDIA DI UDINE - UDINE (UD) ONCOLOGIA MEDICA U.O. Oncologia Medica
Udine, 33100
About this study
Official title: Induction Chemotherapy With Folfoxiri Plus Cetuximab and Maintenance With Cetuximab or Bevacizumab Therapy in Unresectable Kras Wild-type Metastatic Colorectal Cancer Patients
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.
Read the detailed description
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.
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- folfoxiri+cetuximab+surgery+cetuximab, folfoxiri+cetuximab+surgery+bevacizumab
- Keywords
- colorectal cancer,, bevacizumab, cetuximab, folfoxiri, kras wild type
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
folfoxiri+cetuximab+surgery+cetuximabOther
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.
folfoxiri+cetuximab+surgery+bevacizumabOther
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.
| Study group | Role | What they receive |
|---|---|---|
| folfoxiri+cetuximab+surgery+cetuximab | Experimental | 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. Receives: Other: folfoxiri+cetuximab+surgery+cetuximab |
| folfoxiri+cetuximab+surgery+bevacizumab | Experimental | 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. Receives: Other: folfoxiri+cetuximab+surgery+bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: up to 10 months
Secondary outcomes (8)
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.
Measured: 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.
Measured: within 10 months after randomization
Time to strategy failure
It is defined as the time from randomization to one of the followings:
- progression during FOLFOXIRI + cetuximab or during a modified FOLFOXIRI + cetuximab regimen;OR
- progression and decision to not administer FOLFOXIRI + cetuximab or a modified FOLFOXIRI + cetuximab regimen
- introduction of a new agent not included in the study treatment according to randomization arm;OR
- 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.
Measured: 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
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: during the induction and the maintenance phases of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2014 (estimated)
- Study startOct 2011
- Primary completionMar 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 143 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gruppo Oncologico del Nord-Ovest
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Alfredo Falcone, MD, Principal investigator, Polo Oncologico Area Vasta Nord Ovest
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02295930
- Sponsor's protocol ID
- 3306
- Other IDs
- 2011-000840-70
- Acronym
- MACBETH
- Status last verified
- Mar 2015
- First submitted
- 4 Feb 2014
- Last updated
- 12 Mar 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Cremolini C, Antoniotti C, Lonardi S, Aprile G, Bergamo F, Masi G, Grande R, Tonini G, Mescoli C, Cardellino GG, Coltelli L, Salvatore L, Corsi DC, Lupi C, Gemma D, Ronzoni M, Dell'Aquila E, Marmorino F, Di Fabio F, Mancini ML, Marcucci L, Fontanini G, Zagonel V, Boni L, Falcone A. Activity and Safety of Cetuximab Plus Modified FOLFOXIRI Followed by Maintenance With Cetuximab or Bevacizumab for RAS and BRAF Wild-type Metastatic Colorectal Cancer: A Randomized Phase 2 Clinical Trial. JAMA Oncol. 2018 Apr 1;4(4):529-536. doi: 10.1001/jamaoncol.2017.5314.
PubMed 29450468
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Induction Chemotherapy With Folfoxiri Plus Cetuximab and Maintenance With Cetuximab or Bevacizumab Therapy in Unresectable Kras Wild-type Metastatic Colorectal Cancer Patients
- ClinicalTrials.gov ID
- NCT02295930
- Acronym / sponsor ID
- MACBETH / 3306
- Conditions
- Metastatic Colorectal Cancer
- Keywords
- colorectal cancer,, bevacizumab, cetuximab, folfoxiri, kras wild type
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 143 participants (actual)
- Lead sponsor
- Gruppo Oncologico del Nord-OvestUniversity, hospital or other
- Study start
- Oct 2011
- Primary completion
- Mar 2015 (actual)
- First posted
- 20 Nov 2014 (estimated)
- 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.
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.
Detailed description
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| folfoxiri+cetuximab+surgery+cetuximab | Experimental | Other: folfoxiri+cetuximab+surgery+cetuximabInduction 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. |
| folfoxiri+cetuximab+surgery+bevacizumab | Experimental | Other: folfoxiri+cetuximab+surgery+bevacizumabInduction 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Histologically confirmed colorectal adenocarcinoma;
- Availability of formalin-fixed paraffin embedded tumor block from primary and/or metastasis;
- KRAS wild-type status of primary colorectal cancer or related metastasis;
- Unresectable and measurable metastatic disease according to RECIST criteria;
- Male or female, aged > 18 years and < 75 years;
Key exclusion criteria (22 listed)
- Prior palliative chemotherapy;
- Prior treatment with EGFR or VEGF inhibitors;
- Symptomatic peripheral neuropathy > 2 grade NCIC-CTG criteria;
- Presence or history of CNS metastasis;
- Active uncontrolled infections; active disseminated intravascular coagulation;
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 |
|---|---|---|
| folfoxiri+cetuximab+surgery+cetuximabInduction 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. | Other | folfoxiri+cetuximab+surgery+cetuximab |
| folfoxiri+cetuximab+surgery+bevacizumabInduction 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. | Other | folfoxiri+cetuximab+surgery+bevacizumab |
Primary outcome
10 months-progression free rate (10m-PFR)
Time frame: up to 10 months
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.
8 secondary outcomes
Best overall response rate
Time frame: every 8 weeks, up to 60 months
10 month resection rate
Time frame: within 10 months after randomization
Time to strategy failure
Time frame: from randomization, up to 60 months
Time to 2nd progressive disease
Time frame: from randomization, up to 60 months
Progression free survival (PFS)
Time frame: from randomization to first documentation of objective disease progression or death, up to 60 months
Overall survival (OS)
Time frame: as the time from randomization to the date of death, up to 60 months
Toxicity rate
Time frame: during the induction and the maintenance phases of treatment
Overall toxicity rate
Time frame: during the induction and the maintenance phases of treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 2015.
- Derived from this study: PubMed 29450468Cremolini C, Antoniotti C, Lonardi S, Aprile G, Bergamo F, Masi G, Grande R, Tonini G, Mescoli C, Cardellino GG, Coltelli L, Salvatore L, Corsi DC, Lupi C, Gemma D, Ronzoni M, Dell'Aquila E, Marmorino F, Di Fabio F, Mancini ML, Marcucci L, Fontanini G, Zagonel V, Boni L, Falcone A. Activity and Safety of Cetuximab Plus Modified FOLFOXIRI Followed by Maintenance With Cetuximab or Bevacizumab for RAS and BRAF Wild-type Metastatic Colorectal Cancer: A Randomized Phase 2 Clinical Trial. JAMA Oncol. 2018 Apr 1;4(4):529-536. doi: 10.1001/jamaoncol.2017.5314.
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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. This study is not recruiting at the moment.
Alfredo Falcone, MD principal investigator
Polo Oncologico Area Vasta Nord Ovest
22 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing folfoxiri+cetuximab+surgery+cetuximab and folfoxiri+cetuximab+surgery+bevacizumab in people with Metastatic Colorectal Cancer, run by Gruppo Oncologico del Nord-Ovest at 22 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 13 inclusion and 22 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: finished, as of the sponsor's last update on 12 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
10 months-progression free rate (10m-PFR) (time frame: up to 10 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02295930, which also lists 1 linked publication.
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 12 Mar 2015.