Clinical trial NCT01358812: FOLFOXIRI Plus Panitumumab In Kras and Braf Wild-Type Metastatic Colorectal Cancer
Official title: Phase II Trial of FOLFOXIRI Plus Panitumumab as First-Line Treatment for Kras and Braf Wild-Type Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Colo-rectal Cancer
Keywords: RAS Wild-Type
BRAF Wild-Type
Lead sponsor: Gruppo Oncologico del Nord-Ovest
Sponsor class: OTHER
First posted: 2011-05-24
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Response Rate
timeFrame: Up to 3 years (objective response will be evaluated every 8 weeks)
Secondary outcomes:
measure: Progression Free Survival
timeFrame: Up to 3 years
measure: Overall Survival
timeFrame: Up to 3 years
measure: Safety Profile
timeFrame: Up to 3 years
measure: Secondary Radical Surgery on Metastases
timeFrame: Up to 3 years
measure: Analyses of Potential Predictive Factors
timeFrame: Up to 3 years
Other outcomes:
Locations:
city: Arezzo
country: Italy
facility: P.O. Zona Aretina - Ospedale S. Donato Di Arezzo
city: Genova
country: Italy
facility: Istituto Nazionale Per La Ricerca Sul Cancro
city: Milano
country: Italy
facility: IRCCS Ospedale San Raffaele
city: Olbia
country: Italy
facility: Asl Olbia - Uo Oncologia Ospedale San Giovanni Di Dio
city: Padova
country: Italy
facility: Istituto Oncologico Veneto (IOV)
city: Pisa
country: Italy
facility: Polo Oncologico Area Vasta Nord-Ovest
city: Roma
country: Italy
facility: Universita' Campus Bio-Medico Di Roma
city: Sassari
country: Italy
facility: Asl Di Sassari - Ospedale S.S. Annunziata -U.O. Oncologia Medica
city: Siena
country: Italy
facility: Ausl 7 Di Siena
city: Udine
country: Italy
facility: A.O. Universitaria S.Maria Della Misericordia Di Udine
Study officials:
affiliation: Polo Oncologico Area Vasta Nord-Ovest
name: Alfredo Falcone, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.