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

Metastatic Colo-rectal Cancer Clinical Trial

— TRIP  

Official title:

Phase II Trial of FOLFOXIRI Plus Panitumumab as First-Line Treatment for Kras and Braf Wild-Type Metastatic Colorectal Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01358812
• Other study ID #: 2934
• Secondary ID: 2009-014556-29
• Status: Completed
• Phase: Phase 2
• First received: May 19, 2011
• Last updated: March 10, 2015
• Start date: March 2010

Study information

• Verified date: March 2015
• Source: Gruppo Oncologico del Nord-Ovest
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Italian Agency for Drugs (AIFA)
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. primary completion date: October 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colo-rectal Cancer

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
Italy	P.O. Zona Aretina - Ospedale S. Donato Di Arezzo	Arezzo
Italy	Istituto Nazionale Per La Ricerca Sul Cancro	Genova
Italy	IRCCS Ospedale San Raffaele	Milano
Italy	Asl Olbia - Uo Oncologia Ospedale San Giovanni Di Dio	Olbia
Italy	Istituto Oncologico Veneto (IOV)	Padova
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

Sponsors (1)

Lead Sponsor	Collaborator
Gruppo Oncologico del Nord-Ovest

Country where clinical trial is conducted

Italy, 

References & Publications (4)

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. — View Citation

Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocákova I, Ruff P, Blasinska-Morawiec M, Šmakal 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. — View Citation

Falcone A, Ricci S, Brunetti I, Pfanner E, Allegrini G, Barbara C, Crinò 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. — View Citation

Peeters M, Price TJ, Cervantes A, Sobrero AF, Ducreux M, Hotko Y, André 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Secondary	Progression Free Survival	Progression free survival is defined as time from study entry until progression of disease (according to RECIST 1.1) or death from any cause. Patients who are alive without having progressed at the end of the study will be censored at their last radiological assessment.	Up to 3 years	No
Secondary	Overall Survival	Overall survival is defined as the time from study entry until death from any cause. Patients who are alive at the end of the study will be censored at that point.	Up to 3 years	No
Secondary	Safety Profile	Safety Profile is based on the collection of all the adverse events occurring during the study graded by NCI-CTC criteria.	Up to 3 years	Yes
Secondary	Secondary Radical Surgery on Metastases	Secondary Radical Surgery on Metastases is defined as microscopically margin-free complete surgical removal of all residual disease performed during treatment or after its completion allowed by tumoral shrinkage and or desappearance of one or more lesions.	Up to 3 years	No
Secondary	Analyses of Potential Predictive Factors	Exploratory analyses of potential predictive factors and surrogate markers of treatment activity or efficacy.	Up to 3 years	No