NCT02295930

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.

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
143

participants targeted

Target at P75+ for phase_2

Geographic Reach
1 country

22 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 1, 2011

Completed
2.3 years until next milestone

First Submitted

Initial submission to the registry

February 4, 2014

Completed
10 months until next milestone

First Posted

Study publicly available on registry

November 20, 2014

Completed
3 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2015

Completed
Last Updated

March 12, 2015

Status Verified

March 1, 2015

Enrollment Period

3.4 years

First QC Date

February 4, 2014

Last Update Submit

March 11, 2015

Conditions

Metastatic Colorectal Cancer

Keywords

colorectal cancer,bevacizumabcetuximabfolfoxirikras wild type

Outcome Measures

Primary Outcomes (1)

  • 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.

    up to 10 months

Secondary Outcomes (8)

  • Best overall response rate

    every 8 weeks, up to 60 months

  • 10 month resection rate

    within 10 months after randomization

  • Time to strategy failure

    from randomization, up to 60 months

  • Time to 2nd progressive disease

    from randomization, up to 60 months

  • Progression free survival (PFS)

    from randomization to first documentation of objective disease progression or death, up to 60 months

  • +3 more secondary outcomes

Study Arms (2)

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.

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.

Other: folfoxiri+cetuximab+surgery+bevacizumab

Interventions

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+cetuximab
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.

folfoxiri+cetuximab+surgery+bevacizumab

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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)
  • +7 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (22)

A.O.Universitaria Policlinico S.Orsola-Malpighi Di Bologna (Oncologia Medica)

Bologna, Italy, 40138, Italy

Location

AUSL DI FROSINONE - FROSINONE (FR) ONCOLOGIA MEDICA U.O. Oncologia Medica

Frosinone, Italy, 03100, Italy

Location

Ausl 12 Di Viareggio (Lu) - Lido Di Camaiore (Lu) Oncologia Medica

Lucca, Italy, 50053, Italy

Location

AZIENDA OSPEDALIERA DI PERUGIA - OSPEDALE S. MARIA DELLA MISERICORDIA - PERUGIA (PG) ONCOLOGIA MEDICA U.O. Oncologia Medica

Perugia, Italy, 06156, Italy

Location

Polo Oncologico Area Vasta Nord Ovest

Pisa, Italy, 56100, Italy

Location

Ospedale Civile Ss. Antonio E Biagio Di Alessandria - Alessandria (Al) Oncologia Medica

Alessandria, 15100, Italy

Location

Irccs Centro Di Riferimento Oncologico (Cro) - Aviano (Pn)

Aviano, 33081, Italy

Location

Istituto Ospedaliero Fondazione Poliambulanza Di Brescia - Brescia (Bs) Oncologia Medica

Brescia, 25124, Italy

Location

Pres.Ospedal.Spedali Civili Brescia - Brescia (Bs) Oncologia Medic

Brescia, 25125, Italy

Location

Ospedale Armando Businco - Cagliari (Ca) Oncologia Medica

Cagliari, 09121, Italy

Location

Azienza Ospedaliera S. Croce E Carle

Cuneo, 12100, Italy

Location

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

Genova, 16132, Italy

Location

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

Padua, 35128, Italy

Location

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

Pontedera, 56100, Italy

Location

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

Reggio Emilia, 42100, Italy

Location

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

Roma, 00128, Italy

Location

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

Roma, 00161, Italy

Location

Ospedale Fatebenefratelli

Roma, 00186, Italy

Location

Ospedale San Pietro Fatebenefratelli - Roma (Rm) Oncologia Medica

Roma, 00189, Italy

Location

Ospedale Civile Di Sondrio

Sondrio, 23100, Italy

Location

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

Torino, 10134, Italy

Location

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

Udine, 33100, Italy

Location

Related Publications (1)

  • 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.

    PMID: 29450468DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Intestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteNeoplasmsDigestive System DiseasesGastrointestinal DiseasesColonic DiseasesIntestinal DiseasesRectal Diseases

Study Officials

  • Alfredo Falcone, MD

    Polo Oncologico Area Vasta Nord Ovest

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 4, 2014

First Posted

November 20, 2014

Study Start

October 1, 2011

Primary Completion

March 1, 2015

Last Updated

March 12, 2015

Record last verified: 2015-03

Locations

IT(22)