Study Assessing Potential Predictive Tumor Markers in Metastatic Colorectal Cancer

NCT ID: NCT01288339

Last Updated: 2018-05-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 78 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-11-08
• Study Completion Date: 2015-02-13

Brief 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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Panitumumab + FOLFOX (DP)

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.

Group Type: EXPERIMENTAL

Panitumumab + FOLFOX (DP)

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

Panitumumab + FOLFOX (no-DP)

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: collaborator

TFS Trial Form Support

INDUSTRY

Sponsor Role: collaborator

Grupo Espanol Multidisciplinario del Cancer Digestivo

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Joan Maurel, MD

Role: STUDY_CHAIR

Hospital Clinic i provincial de Barcelona

Marta Martín, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital de la Santa Creu i Sant Pau de Barcelona

Antonia Salud, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Arnau de Vilanova de Lleida

Antonio Arrivi, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Son Llatzer de Mallorca

Xavier Hernández, MD

Role: PRINCIPAL_INVESTIGATOR

Intitut Català d' Oncologia (ICO) de Girona

Ólbia Serra, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital General de l'Hospitalet de Barcelona

Carles Pericay, MD

Role: PRINCIPAL_INVESTIGATOR

Corporació Sanitaria Parc Taulí de Barcelona

Isabel Busquier, MD

Role: PRINCIPAL_INVESTIGATOR

Consorcio Hospitalario Provincial de Castellon

Carlos Fernandez-Martos, MD

Role: PRINCIPAL_INVESTIGATOR

Instituto Valenciano de Oncología de Valencia

Jorge Aparicio, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitario La Fe de Valencia

Maria José Safont, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital General Universitario de Valencia

Carles Bosch, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Dr. Peset de Valencia

Javier Gallego, MD

Role: PRINCIPAL_INVESTIGATOR

Hosptial General Universitario de Elche

Alberto Carmona, MD

Role: PRINCIPAL_INVESTIGATOR

Hosptial Morales Meseguer

Jaume Feliu, MD

Role: PRINCIPAL_INVESTIGATOR

Hosptial Universitario La Paz de Madrid

Ana Ruíz, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital de Fuenlabrada de Madrid

Enrique Casado, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Infanta Sofía de Madrid

Ricardo Cubedo, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitario Puerta de Hierro de Madrid

Juana Maria Cano, MD

Role: PRINCIPAL_INVESTIGATOR

Hosptial General de Ciudad Real

Vicente Alonso, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Miguel Servet de Zaragoza

Monica Jorge, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Xeral Cies de Vigo

Herminio Manzano, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Son Dureta de Mallorca

Javier Rodríguez, MD

Role: PRINCIPAL_INVESTIGATOR

Clínica Universitaria de Navarra

Uriel Bohn, MD

Role: PRINCIPAL_INVESTIGATOR

Hosptial Dr. Negrin de Las Palmas de Gran Canaria

Miriam Zorrilla, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital de Logroño

Ruth Vera, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital de Navarra

Carlos García, MD

Role: PRINCIPAL_INVESTIGATOR

Complejo Asistencial de Burgos. Hospital General Yague

Santiago Albiol, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital de l'Esperit Sant de Barcelona

José Carlos Méndez, MD

Role: PRINCIPAL_INVESTIGATOR

Centro Oncológico de Galicia (La Coruña)

Francisco Javier Ramos, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital de Sant Pau i Santa Tecla de Tarragona

Locations

Hospital General Universitario de Elche

Elche, Alicante, Spain

Hospital Son Espases de Mallorca

Palma de Mallorca, Balearic Islands, Spain

Hosptial Son Llatzer de Mallorca

Palma de Mallorca, Balearic Islands, Spain

Hosptial General de l'Hospitalet de Barcelona

L'Hospitalet de Llobregat, Barcelona, Spain

Corporació Sanitaria Parc Taulí de Barcelona

Sabadell, Barcelona, Spain

Hospital de l'Esperit Sant

Santa Coloma de Gramenet, Barcelona, Spain

Consorcio Hospitalario Provincial de Castellon

Castellon, Castellon, Spain

Hosptial de Logroño

Logroño, La Rioja, Spain

Hospital Universitario La Paz de Madrid

Madrid, Madrdi, Spain

Clínica Universitaria de Navarra

Pamplona, Navarre, Spain

Hospital de Navarra

Pamplona, Navarre, Spain

Hospital Xeral Cies de Vigo

Vigo, Pontevedra, Spain

Centro Oncológico de Galícia

A Coruña, , Spain

Hospital Clínic i Provincial de Barcelona

Barcelona, , Spain

Hospital de la Santa Creu i Sant Pau de Barcelona

Barcelona, , Spain

Complejo Asitencia de Burgos. Hospital General Yague

Burgos, , Spain

Hospital General de Ciudad Real

Ciudad Real, , Spain

Institut Català d'Oncologia (ICO) de Girona

Girona, , Spain

Hosptial Dr. Negrin de Las Palmas de Gran Canaria

Las Palmas de Gran Canaria, , Spain

Hospital Arnau de Vilanova de Lleida

Lleida, , Spain

Hospital Infanta Sofía de Madrid

Madrid, , Spain

Hospital Universitario Puerta de Hierro de Madrid

Madrid, , Spain

Hospital de Fuenlabrada de Madrid

Madrid, , Spain

Hospital Morales Meseguer

Murcia, , Spain

Hosptial de Sant Pau i Santa Tecla de Tarragona

Tarragona, , Spain

Hospital La Fe de Valencia

Valencia, , Spain

Instituto Valenciano de Oncología de Valencia

Valencia, , Spain

Hospital General de Valencia

Valencia, , Spain

Hospital Dr. Peset de Valencia

Valencia, , Spain

Hospital Miguel Servet de Zaragoza

Zaragoza, , Spain

Countries

Spain

References

Maurel J, Alonso V, Escudero P, Fernandez-Martos C, Salud A, Mendez M, Gallego J, Rodriguez JR, Martin-Richard M, Fernandez-Plana J, Manzano H, Mendez JC, Zanui M, Falco E, Gil-Raga M, Aparicio J, Feliu J, Garcia-Albeniz X, Torres F, Rojo F, Bellosillo B, Mendiola M, Fernandez V, Reig O, Claes B, Maertens G, Sablon E, Jacobs B, Montagut C. Clinical Impact of Circulating Tumor RAS and BRAF Mutation Dynamics in Patients With Metastatic Colorectal Cancer Treated With First-Line Chemotherapy Plus Anti-Epidermal Growth Factor Receptor Therapy. JCO Precis Oncol. 2019 Dec;3:1-16. doi: 10.1200/PO.18.00289.

Reference Type: DERIVED

PMID: 35100697 (View on PubMed)

Other Identifiers

2009-017331-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GEMCAD-0903

Identifier Type: -

Identifier Source: org_study_id