NCT01358812

Brief Summary

The GONO-FOLFOXIRI regimen demonstrated higher activity and efficacy compared to FOLFIRI in a phase III trial. Panitumumab with oxaliplatin- or irinotecan-based doublets is feasible and associated with improved activity in KRAS codon 12-13 wild-type patients. BRAF and other RAS rare mutations have been suggested as additional potential biomarkers for anti-EGFR agents in metastatic colo-rectal cancer. The present study aims to demonstrate the feasibility and the activity of the first-line combination of the GONO-FOLFOXIRI regimen and Panitumumab in molecularly selected metastatic colo-rectal cancer patients.

Trial Health

80
On Track

Trial Health Score

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

Enrollment
37

participants targeted

Target at P25-P50 for phase_2

Geographic Reach
1 country

10 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

March 1, 2010

Completed
1.2 years until next milestone

First Submitted

Initial submission to the registry

May 19, 2011

Completed
5 days until next milestone

First Posted

Study publicly available on registry

May 24, 2011

Completed
4 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2011

Completed
Last Updated

March 11, 2015

Status Verified

March 1, 2015

Enrollment Period

1.6 years

First QC Date

May 19, 2011

Last Update Submit

March 10, 2015

Conditions

Metastatic Colo-rectal Cancer

Keywords

RAS Wild-TypeBRAF Wild-Type

Outcome Measures

Primary Outcomes (1)

  • Response Rate

    Response rate is defined as the fraction of treated patients who achieve a response as defined according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria vers. 1.1.

    Up to 3 years (objective response will be evaluated every 8 weeks)

Secondary Outcomes (5)

  • Progression Free Survival

    Up to 3 years

  • Overall Survival

    Up to 3 years

  • Safety Profile

    Up to 3 years

  • Secondary Radical Surgery on Metastases

    Up to 3 years

  • Analyses of Potential Predictive Factors

    Up to 3 years

Study Arms (1)

FOLFOXIRI + Panitumumab

EXPERIMENTAL

PANITUMUMAB 6 mg/Kg i.v. over 1 hour followed by IRINOTECAN 150 mg/sqm i.v. over 1 hour followed by OXALIPLATIN 85 mg/sqm i.v. over 2 hours concomitantly with L-LV 200 mg/sqm over 2 hours followed by 5-FLUOROURACIL 2400 mg/sqm c.i. over 48 hours starting on day 1 repeated every 2 weeks.

Drug: FOLFOXIRI + Panitumumab

Interventions

FOLFOXIRI + PanitumumabDRUG

PANITUMUMAB 6 mg/Kg i.v. over 1 hour followed by IRINOTECAN 150 mg/sqm i.v. over 1 hour followed by OXALIPLATIN 85 mg/sqm i.v. over 2 hours concomitantly with L-LV 200 mg/sqm over 2 hours followed by 5-FLUOROURACIL\* 2400 mg/sqm c.i. over 48 hours starting on day 1 repeated every 2 weeks.

FOLFOXIRI + Panitumumab

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 or metastasis;
  • KRAS and BRAF 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 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 is allowed if more than 12 months have elapsed between the end of adjuvant therapy and first relapse;
  • At least 6 weeks from prior radiotherapy and 4 weeks from surgery;
  • Written informed consent to experimental treatment and pharmacogenomic analyses;
  • Magnesium ≥ lower limit of normal;
  • +1 more criteria

You may not qualify if:

  • Prior palliative chemotherapy;
  • Prior treatment with EGFR 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, for example cerebrovascular accidents (CVA) (≤ 6 months before treatment start), myocardial infarction (≤ 6 months before treatment start), unstable angina, NYHA ≥ grade 2 chronic heart failure (CHF), uncontrolled arrhythmia;
  • Fertile women (\< 2 years after last menstruation) and men of childbearing potential not willing to use effective means of contraception;
  • Subject pregnant or breast feeding, or planning to become pregnant within 6 months after the end of treatment;
  • History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (10)

P.O. Zona Aretina - Ospedale S. Donato Di Arezzo

Arezzo, Italy

Location

Istituto Nazionale Per La Ricerca Sul Cancro

Genova, 16132, Italy

Location

IRCCS Ospedale San Raffaele

Milan, 20132, Italy

Location

Asl Olbia - Uo Oncologia Ospedale San Giovanni Di Dio

Olbia, 07026, Italy

Location

Istituto Oncologico Veneto (IOV)

Padua, 35100, Italy

Location

Polo Oncologico Area Vasta Nord-Ovest

Pisa, 56126, Italy

Location

Universita' Campus Bio-Medico Di Roma

Roma, 00128, Italy

Location

Asl Di Sassari - Ospedale S.S. Annunziata -U.O. Oncologia Medica

Sassari, 07100, Italy

Location

Ausl 7 Di Siena

Siena, 53100, Italy

Location

A.O. Universitaria S.Maria Della Misericordia Di Udine

Udine, 33100, Italy

Location

Related Publications (4)

  • Falcone A, Ricci S, Brunetti I, Pfanner E, Allegrini G, Barbara C, Crino L, Benedetti G, Evangelista W, Fanchini L, Cortesi E, Picone V, Vitello S, Chiara S, Granetto C, Porcile G, Fioretto L, Orlandini C, Andreuccetti M, Masi G; Gruppo Oncologico Nord Ovest. Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest. J Clin Oncol. 2007 May 1;25(13):1670-6. doi: 10.1200/JCO.2006.09.0928.

    PMID: 17470860BACKGROUND

  • Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocakova I, Ruff P, Blasinska-Morawiec M, Smakal M, Canon JL, Rother M, Oliner KS, Wolf M, Gansert J. Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol. 2010 Nov 1;28(31):4697-705. doi: 10.1200/JCO.2009.27.4860. Epub 2010 Oct 4.

    PMID: 20921465BACKGROUND

  • Peeters M, Price TJ, Cervantes A, Sobrero AF, Ducreux M, Hotko Y, Andre T, Chan E, Lordick F, Punt CJ, Strickland AH, Wilson G, Ciuleanu TE, Roman L, Van Cutsem E, Tzekova V, Collins S, Oliner KS, Rong A, Gansert J. Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol. 2010 Nov 1;28(31):4706-13. doi: 10.1200/JCO.2009.27.6055. Epub 2010 Oct 4.

    PMID: 20921462BACKGROUND

  • De Roock W, Claes B, Bernasconi D, De Schutter J, Biesmans B, Fountzilas G, Kalogeras KT, Kotoula V, Papamichael D, Laurent-Puig P, Penault-Llorca F, Rougier P, Vincenzi B, Santini D, Tonini G, Cappuzzo F, Frattini M, Molinari F, Saletti P, De Dosso S, Martini M, Bardelli A, Siena S, Sartore-Bianchi A, Tabernero J, Macarulla T, Di Fiore F, Gangloff AO, Ciardiello F, Pfeiffer P, Qvortrup C, Hansen TP, Van Cutsem E, Piessevaux H, Lambrechts D, Delorenzi M, Tejpar S. Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis. Lancet Oncol. 2010 Aug;11(8):753-62. doi: 10.1016/S1470-2045(10)70130-3. Epub 2010 Jul 8.

    PMID: 20619739BACKGROUND

MeSH Terms

Conditions

Colonic Neoplasms

Interventions

Panitumumab

Condition Hierarchy (Ancestors)

Colorectal NeoplasmsIntestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteNeoplasmsDigestive System DiseasesGastrointestinal DiseasesColonic DiseasesIntestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • Alfredo Falcone, MD

    Polo Oncologico Area Vasta Nord-Ovest

    PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

First Submitted

May 19, 2011

First Posted

May 24, 2011

Study Start

March 1, 2010

Primary Completion

October 1, 2011

Last Updated

March 11, 2015

Record last verified: 2015-03

Locations

IT(10)