Induction Chemoterapy With Folfoxiri Plus Cetuxumab in Unresectable Colorectal Cancer Patient

NCT ID: NCT02295930

Last Updated: 2015-03-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 143 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-10-31

Brief 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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

folfoxiri+cetuximab+surgery+cetuximab

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.

Group Type: EXPERIMENTAL

folfoxiri+cetuximab+surgery+cetuximab

Intervention Type: OTHER

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+bevacizumab

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.

Group Type: EXPERIMENTAL

folfoxiri+cetuximab+surgery+bevacizumab

Intervention Type: OTHER

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.

Interventions

folfoxiri+cetuximab+surgery+cetuximab

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.

Intervention Type: OTHER

folfoxiri+cetuximab+surgery+bevacizumab

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.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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;
• 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.

Exclusion Criteria

• 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;
• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gruppo Oncologico del Nord-Ovest

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alfredo Falcone, MD

Role: PRINCIPAL_INVESTIGATOR

Polo Oncologico Area Vasta Nord Ovest

Locations

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

Azienza Ospedaliera S. Croce E Carle

Cuneo, , Italy

IRCCS ISTITUTO NAZIONALE PER LA RICERCA SUL CANCRO (IST) - GENOVA (GE) ONCOLOGIA MEDICA Oncologia Medica A

Genova, , Italy

Irccs Istituto Oncologico Veneto (Iov) - Padova (Pd) Oncologia Medica

Padua, , Italy

AUSL 5 DI PISA - PISA (PI) ONCOLOGIA MEDICA oncologia medica Osp Lotti Pontedera

Pontedera, , Italy

Ospedale Di S. Maria Nuova - Reggio Nell'Emilia (Re) Oncologia Medica

Reggio Emilia, , Italy

Policlinico Universitario Campus Bio-Medico Di Roma - Roma (Rm) Oncologia Medica

Roma, , Italy

POLICLINICO UMBERTO I DI ROMA - ROMA (RM) ONCOLOGIA MEDICA oncologia Medica

Roma, , Italy

Ospedale Fatebenefratelli

Roma, , Italy

Ospedale San Pietro Fatebenefratelli - Roma (Rm) Oncologia Medica

Roma, , Italy

Ospedale Civile Di Sondrio

Sondrio, , Italy

A.O. Universitaria S. Giovanni Battista-Molinette Di Torino - Torino (to) Oncologia Medica

Torino, , Italy

A.O. UNIVERSITARIA S. MARIA DELLA MISERICORDIA DI UDINE - UDINE (UD) ONCOLOGIA MEDICA U.O. Oncologia Medica

Udine, , Italy

Countries

Italy

References

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.

Reference Type: DERIVED

PMID: 29450468 (View on PubMed)

Other Identifiers

2011-000840-70

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

3306

Identifier Type: -

Identifier Source: org_study_id