FOLFOXIRI Plus Panitumumab In Kras and Braf Wild-Type Metastatic Colorectal Cancer

NCT ID: NCT01358812

Last Updated: 2015-03-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 37 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-03-31

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.

Conditions

Metastatic Colo-rectal Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

FOLFOXIRI + Panitumumab

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.

Group Type: EXPERIMENTAL

FOLFOXIRI + Panitumumab

Intervention Type: DRUG

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.

Interventions

FOLFOXIRI + Panitumumab

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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;
• Calcium ≥ lower limit of normal.

Exclusion Criteria

• 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.

• 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

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

Arezzo, , Italy

Istituto Nazionale Per La Ricerca Sul Cancro

Genova, , Italy

IRCCS Ospedale San Raffaele

Milan, , Italy

Asl Olbia - Uo Oncologia Ospedale San Giovanni Di Dio

Olbia, , Italy

Istituto Oncologico Veneto (IOV)

Padua, , Italy

Polo Oncologico Area Vasta Nord-Ovest

Pisa, , Italy

Universita' Campus Bio-Medico Di Roma

Roma, , Italy

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

Sassari, , Italy

Ausl 7 Di Siena

Siena, , Italy

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

Udine, , Italy

Countries

Italy

References

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.

Reference Type: BACKGROUND

PMID: 17470860 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 20921465 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 20921462 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 20619739 (View on PubMed)

Other Identifiers

2009-014556-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2934

Identifier Type: -

Identifier Source: org_study_id