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