An Open Label, Phase II Study Assessing Potential Predictive Tumor Markers in Patients With Metastatic Colorectal Cancer and Wild Type K-RAS Tumor Treated With FOLFOX Plus Panitumumab as First-line Therapy
By transactivation, phosphorylated insulin growth factor receptor I (p-IGF-IR) can activate
epidermal growth factor receptor (EGFR). Matrilysin (MMP-7), can activate IGF-IR
(insulin-like growth factor receptor ) by degrading IGFBP-3 (Insulin-like growth
factor-binding protein 3) and releasing IGF-I (Insulin-like growth factor 1). 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 (Double Positivity)) correlates
with poor prognosis in WT KRAS patients treated with anti-EGFR antibodies plus
irinotecan.The primary objective of this trial is to estimate the progression free survival
(PFS) by DP (Double Positivity)immunohistochemistry (IHC) expression in patients with
wild-type KRAS mCRC (metastatic colorectal cancer)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. Neither interim analysis nor multiple comparison adjustment is
planned.Treatment: Both groups will receive panitumumab 6 mg/kg and mFOLFOX6 every 2 weeks.
If patients have not progressed after 6 m of treatment they will continue with panitumumab
monotherapy until disease progression.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Progression-free survival time according to the MMP7 status (PFS)
To estimate the 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-).
Joan Maurel, Dr.
Hospital Clinic i Provincial de Barcelona
Spain: Spanish Agency of Medicines