Overview

This trial is active, not recruiting.

Condition metastatic colorectal cancer
Treatments panitumumab + folfox (dp), panitumumab + folfox (no-dp)
Phase phase 2
Sponsor Grupo Espanol Multidisciplinario del Cancer Digestivo
Collaborator Amgen
Start date November 2010
End date January 2015
Trial size 80 participants
Trial identifier NCT01288339, 2009-017331-18, GEMCAD-0903

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Panitumumab and FOLFOX will be administered to patients with DP (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.
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.
(Experimental)
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.
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.

Primary Outcomes

Measure
Progression-free survival time according to the MMP7 status (PFS)
time frame: 5 years

Secondary Outcomes

Measure
Duration of response (DOR)
time frame: 5 years
Time to response (TTR)
time frame: 5 years
Time to treatment failure (TtTF)
time frame: 5 years
Objective response rate (ORR)
time frame: 5 years
Disease Control Rate (DCR)
time frame: 5 years
Overall Survival (OS)
time frame: 5 years
Time To Progression (TTP)
time frame: 5 years
Duration of Stable Disease (DoSD)
time frame: 5 years
Incidence and severity of AEs
time frame: 5 years
Molecular predictive markers for response.
time frame: 5 years

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Man or woman ≥ 18 years. - Competent to comprehend, sign, and date an IEC-approved (Ethics Committee) informed consent form - Histologically-confirmed metastatic adenocarcinoma of the colon or rectum by the investigator. - Wild Type K-RAS colorectal cancer determined by the designated Central Laboratory prior to inclusion in the study in the primary tumor and/or at least one metastasis. - At least 1 uni-dimensionally measurable lesion of at least > 10 mm with spiral CT per modified RECIST criteria 1.1. (Response Evaluation Criteria In Solid Tumors) - Patients with the following characteristics will be included: 1. Recurrence after adjuvant treatment with 5-fluorouracil/folinic acid or capecitabine +/- radiotherapy with a disease-free interval > than 6 months after its completion. 2. Recurrence after adjuvant treatment with oxaliplatin +/- radiotherapy with a disease-free interval > than 12 months 3. De novo diagnosis of the disease. - Eastern Cooperative Oncology Group performance status of 0 or 1. - Life expectancy ≥ 3 months - Adequate bone marrow function - Adequate Hepatic and metabolic functions - Adequate Renal function - Magnesium > LLN (Lower limit of Normal) Exclusion Criteria: - Patients they have received prior systemic therapy for the treatment of metastatic colorectal carcinoma. - Prior anti-EGFr antibody therapy (eg, cetuximab) or treatment small molecule EGFr tyrosine kinase inhibitors (eg, erlotinib) or EGFR signal transduction inhibitors. - Patients who had resection of metastatic disease - Central nervous system/brain metastases - Prior malignant tumor in the last 5 years, except a history of basal cell carcinoma of the skin or pre-invasive cervical cancer. - Unresolved toxicities from prior systemic therapy that, in the opinion of the investigator, does not qualify the patient for inclusion - Presence of peripheral neuropathy (Common Toxicity Criteria (CTC) version 3.0 > grade 1), and of serious nonhealing wound, ulcer, or bone fracture. - Hormonal therapy, immunotherapy or experimental or approved proteins/antibodies (eg, bevacizumab) ≤ 30 days before inclusion - Significant cardiovascular disease including unstable angina or myocardial infarction within 12 months before initiating study treatment or a history of ventricular arrhythmia. - History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis on baseline chest CT scan - Treatment for systemic infection within 14 days before initiating study treatment - Acute or sub-acute intestinal occlusion and /or active inflammatory bowel disease or other bowel disease causing chronic diarrhea (defined as > 4 loose stools per day). - Known positive test for human immunodeficiency virus infection, hepatitis C virus, chronic active hepatitis B infection - Any investigational agent within 30 days before enrollment - Subject who is pregnant or breast feeding - Surgery (excluding diagnostic biopsy or central venous catheter placement) and/or radiotherapy within 14 days prior to inclusion in the study. - Woman or man of childbearing potential not consenting to use adequate contraceptive precautions

Additional Information

Official title 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
Principal investigator Marta Martín, Dra.
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.
Trial information was received from ClinicalTrials.gov and was last updated in March 2015.
Information provided to ClinicalTrials.gov by Grupo Espanol Multidisciplinario del Cancer Digestivo.