Clinical trial NCT02295930: Induction Chemoterapy With Folfoxiri Plus Cetuxumab in Unresectable Colorectal Cancer Patient
Official title: Induction Chemotherapy With Folfoxiri Plus Cetuximab and Maintenance With Cetuximab or Bevacizumab Therapy in Unresectable Kras Wild-type Metastatic Colorectal Cancer Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Keywords: colorectal cancer,
bevacizumab
cetuximab
folfoxiri
kras wild type
Lead sponsor: Gruppo Oncologico del Nord-Ovest
Sponsor class: OTHER
First posted: 2014-11-20
Enrollment: 143
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: 10 months-progression free rate (10m-PFR)
timeFrame: up to 10 months
Secondary outcomes:
measure: Best overall response rate
timeFrame: every 8 weeks, up to 60 months
measure: 10 month resection rate
timeFrame: within 10 months after randomization
measure: Time to strategy failure
timeFrame: from randomization, up to 60 months
measure: Time to 2nd progressive disease
timeFrame: from randomization, up to 60 months
measure: Progression free survival (PFS)
timeFrame: from randomization to first documentation of objective disease progression or death, up to 60 months
measure: Overall survival (OS)
timeFrame: as the time from randomization to the date of death, up to 60 months
measure: Toxicity rate
timeFrame: during the induction and the maintenance phases of treatment
measure: Overall toxicity rate
timeFrame: during the induction and the maintenance phases of treatment
Other outcomes:
Locations:
city: Alessandria
country: Italy
facility: Ospedale Civile Ss. Antonio E Biagio Di Alessandria - Alessandria (Al) Oncologia Medica
city: Aviano
country: Italy
facility: Irccs Centro Di Riferimento Oncologico (Cro) - Aviano (Pn)
city: Bologna
country: Italy
facility: A.O.Universitaria Policlinico S.Orsola-Malpighi Di Bologna (Oncologia Medica)
city: Brescia
country: Italy
facility: Istituto Ospedaliero Fondazione Poliambulanza Di Brescia - Brescia (Bs) Oncologia Medica
city: Brescia
country: Italy
facility: Pres.Ospedal.Spedali Civili Brescia - Brescia (Bs) Oncologia Medic
city: Cagliari
country: Italy
facility: Ospedale Armando Businco - Cagliari (Ca) Oncologia Medica
city: Cuneo
country: Italy
facility: Azienza Ospedaliera S. Croce E Carle
city: Frosinone
country: Italy
facility: AUSL DI FROSINONE - FROSINONE (FR) ONCOLOGIA MEDICA U.O. Oncologia Medica
city: Genova
country: Italy
facility: IRCCS ISTITUTO NAZIONALE PER LA RICERCA SUL CANCRO (IST) - GENOVA (GE) ONCOLOGIA MEDICA Oncologia Medica A
city: Lucca
country: Italy
facility: Ausl 12 Di Viareggio (Lu) - Lido Di Camaiore (Lu) Oncologia Medica
city: Padova
country: Italy
facility: Irccs Istituto Oncologico Veneto (Iov) - Padova (Pd) Oncologia Medica
city: Perugia
country: Italy
facility: AZIENDA OSPEDALIERA DI PERUGIA - OSPEDALE S. MARIA DELLA MISERICORDIA - PERUGIA (PG) ONCOLOGIA MEDICA U.O. Oncologia Medica
city: Pisa
country: Italy
facility: Polo Oncologico Area Vasta Nord Ovest
city: Pontedera
country: Italy
facility: AUSL 5 DI PISA - PISA (PI) ONCOLOGIA MEDICA oncologia medica Osp Lotti Pontedera
city: Reggio Emilia
country: Italy
facility: Ospedale Di S. Maria Nuova - Reggio Nell'Emilia (Re) Oncologia Medica
city: Roma
country: Italy
facility: Policlinico Universitario Campus Bio-Medico Di Roma - Roma (Rm) Oncologia Medica
city: Roma
country: Italy
facility: POLICLINICO UMBERTO I DI ROMA - ROMA (RM) ONCOLOGIA MEDICA oncologia Medica
city: Roma
country: Italy
facility: Ospedale Fatebenefratelli
city: Roma
country: Italy
facility: Ospedale San Pietro Fatebenefratelli - Roma (Rm) Oncologia Medica
city: Sondrio
country: Italy
facility: Ospedale Civile Di Sondrio
city: Torino
country: Italy
facility: A.O. Universitaria S. Giovanni Battista-Molinette Di Torino - Torino (to) Oncologia Medica
city: Udine
country: Italy
facility: A.O. UNIVERSITARIA S. MARIA DELLA MISERICORDIA DI UDINE - UDINE (UD) ONCOLOGIA MEDICA U.O. Oncologia Medica
Study officials:
affiliation: Polo Oncologico Area Vasta Nord Ovest
name: Alfredo Falcone, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.