FOLFOXIRI Plus Panitumumab In Kras and Braf Wild-Type Metastatic Colorectal Cancer
- Conditions
- Metastatic Colo-rectal Cancer
- Interventions
- Drug: FOLFOXIRI + Panitumumab
- Registration Number
- NCT01358812
- Lead Sponsor
- Gruppo Oncologico del Nord-Ovest
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 37
- 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.
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description FOLFOXIRI + Panitumumab 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.
- Primary Outcome Measures
Name Time Method Response Rate Up to 3 years (objective response will be evaluated every 8 weeks) 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.
- Secondary Outcome Measures
Name Time Method Safety Profile Up to 3 years Safety Profile is based on the collection of all the adverse events occurring during the study graded by NCI-CTC criteria.
Analyses of Potential Predictive Factors Up to 3 years Exploratory analyses of potential predictive factors and surrogate markers of treatment activity or efficacy.
Overall Survival Up to 3 years 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.
Secondary Radical Surgery on Metastases Up to 3 years 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.
Progression Free Survival Up to 3 years 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.
Trial Locations
- Locations (10)
P.O. Zona Aretina - Ospedale S. Donato Di Arezzo
🇮🇹Arezzo, Italy
IRCCS Ospedale San Raffaele
🇮🇹Milano, Italy
Istituto Nazionale Per La Ricerca Sul Cancro
🇮🇹Genova, 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
Ausl 7 Di Siena
🇮🇹Siena, Italy
Asl Di Sassari - Ospedale S.S. Annunziata -U.O. Oncologia Medica
🇮🇹Sassari, Italy
A.O. Universitaria S.Maria Della Misericordia Di Udine
🇮🇹Udine, Italy