BACKGROUND: By transactivaction, p-IGF-IR can activate epidermal growth factor receptor (EGFR). Matrilysin (MMP-7), can activate IGF-IR by degrading IGFBP-3 and releasing IGF-I. Concomitant expression of MMP-7 and p-IGF-IR (using a specific monoclonal antibody (p-1316) recognizing the phosphorylated carboxy-terminal part of the IGF-IR) (DP) correlates with poor prognosis in WT KRAS pts treated with anti-EGFR antibodies plus irinotecan (Horndler et al, Cancer Biol Ther 2011).
METHODS: Trial Design: the primary objective of this trial is to estimate the progression free survival (PFS) by DP immunohistochemistry (IHC) expression in patients with wild-type KRAS mCRC treated with panitumumab and mFOLFOX6. Two groups are established by DP status (MMP7+/p-IGF-IR+ vs. MMP7+/p-IGF-IR-, MMP7-/p-IGF-IR+ or MMP7-/p-IGF-IR-). With a power of 80% and a bilateral alpha level of 0.05, assuming an accrual period of 12 months (m) and a follow-up period of 18 m, 40 patients are planned to be included in each group to detect a Hazard Ratio of 2. The median PFS of the DP group is expected to be 6 m and the total number of expected events is 56. Secondary objectives include disease control rate, duration of response, time to response and survival according the DP status. Treatment: Both groups will receive panitumumab 6 mg/kg and mFOLFOX6 every 2 weeks. If pts have not progressed after 6 m of treatment they will continue with panitumumab monotherapy until disease progression. Major eligibility criteria: Previously untreated wild type KRAS mCRC, ECOG PS of 0 or 1, at least 1 unidimensionally measurable lesion, and age > 18 years. Correlative studies: PTEN and p-EGFR by IHC and BRAF, PI3K, PTEN, IGFR-II, EGFR (3’) and NRAS mutations according microsatellite instability. Blood sample collection (MMP-7, IGFBP-2,3,5, IGF-I and IGF-II) basally and every 2 month until progressive disease. The study has just initiated enrollment.
