NCT01288339

Study Assessing Potential Predictive Tumor Markers in Metastatic Colorectal Cancer

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

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 78 (actual)
• Sponsor: Grupo Espanol Multidisciplinario del Cancer Digestivo · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

To estimate the progression free survival for subjects treated with panitumumab in combination with a chemotherapy regimen of oxaliplatin, 5-Fluorouracil (5-FU) and leucovorin (FOLFOX) as first-line chemotherapy regimen for subjects with metastatic colorectal cancer with WT (wild type) KRAS according to the IGFRp (protein receptor insulin growth factor) and MMP-7 (Matrilysin) expression.

Detailed description

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.

Conditions

• Metastatic Colorectal Cancer

Interventions

Type	Name	Description
DRUG	Panitumumab + FOLFOX (DP)	Panitumumab and FOLFOX will be administered to patients with DP once every 14 days until 6 months of treatment or until disease progression (PD) or unacceptable toxicity. If patients have not progressed after 6 months of treatment with panitumumab and FOLFOX they will continue with panitumumab monotherapy until disease progression.
DRUG	Panitumumab + FOLFOX (no-DP)	Panitumumab and FOLFOX will be administered to patients with no-DP (MMP7+/p-IGF-IR-, MMP7-/p-IGF-IR+ or MMP7-/p-IGF-IR) once every 14 days until 6 months of treatment or until disease progression (PD) or unacceptable toxicity. If patients have not progressed after 6 months of treatment with panitumumab and FOLFOX they will continue with panitumumab monotherapy until disease progression.

Timeline

• Start date: 2010-11-08
• Primary completion: 2015-02-13
• Completion: 2015-02-13
• First posted: 2011-02-02
• Last updated: 2018-05-16

Locations

30 sites across 1 country: Spain