Prognostic Factors for Patients With Advanced Colorectal Cancer Treated With Cetuximab.

NCT ID: NCT01068132

Last Updated: 2014-05-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-04-30
• Study Completion Date: 2013-10-31

Brief Summary

Italian, multicentre, non comparative trial in patients with advanced Colorectal Cancer(CRC)and KRAS wild-type, defined by molecular evaluation.

Patients will receive Cetuximab + FOLFIRI until disease progression, unacceptable toxicity developed or patient refusal.

The aim of this study is to assess the prognostic role of PTEN in terms of Progression free survival.

Although the role of Cetuximab as first line treatment in metastatic CRC will be soon established, it is still unclear which is the best schedule for Cetuximab and the role of biological factors in order to select the most appropriate subset of pts for recommending Cetuximab. The data supporting a benefit of Cetuximab in KRAS wild-type pts open the perspective to study the role of other molecular markers in this subset of pts.

On the basis of these considerations this study is aimed at testing a different schedule of Cetuximab and better characterize the prognosis of pts for which Cetuximab is appropriate.

Detailed Description

Pts meeting eligibility criteria will be registered, providing the availability of material for molecular analysis. Tumour specimens and blood sample will be collected to perform genomic, ICH and proteomic analyses in order to identify the molecular characteristics of tumour.

After the availability of KRAS evaluation, only the data of KRAS wild-type pts will be collected.

Access to registration system will be allowed via web.

Patients,KRAS wild-type receive:

• Cetuximab+FOLFIRI: cetuximab 500 mg/ m² starting dose, following everytwo- week doses of 500 mg/ m², given d1, followed after 1 hour by FOLFIRI: irinotecan 180 mg/m2 on day 1 with LV 100 mg/m2 administered as a 2-hour infusion before FU 400 mg/m2 administered as an intravenous bolus injection, and FU 600 mg/m2 as a 22-hour infusion immediately after FU bolus injection on days 1 and 2

Conditions

Colorectal Cancer

Study Design

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

Study Groups

1

Cetuximab+FOLFIRI: cetuximab 500 mg/ m² starting dose, following everytwo- week doses of 500 mg/ m², given d1, followed after 1 hour by FOLFIRI: irinotecan 180 mg/m2 on day 1 with LV 100 mg/m2 administered as a 2-hour infusion before FU 400 mg/m2 administered as an intravenous bolus injection, and FU 600 mg/m2 as a 22-hour infusion immediately after FU bolus injection on days 1 and 2

Group Type: EXPERIMENTAL

Cetuximab

Intervention Type: DRUG

cetuximab 500 mg/ m² starting dose, following everytwo- week doses of 500 mg/ m², given d1,

FOLFIRI

Intervention Type: DRUG

irinotecan 180 mg/m2 on day 1 with LV 100 mg/m2 administered as a 2-hour infusion before FU 400 mg/m2 administered as an intravenous bolus injection, and FU 600 mg/m2 as a 22-hour infusion immediately after FU bolus injection on days 1 and 2

Interventions

Cetuximab

cetuximab 500 mg/ m² starting dose, following everytwo- week doses of 500 mg/ m², given d1,

Intervention Type: DRUG

FOLFIRI

irinotecan 180 mg/m2 on day 1 with LV 100 mg/m2 administered as a 2-hour infusion before FU 400 mg/m2 administered as an intravenous bolus injection, and FU 600 mg/m2 as a 22-hour infusion immediately after FU bolus injection on days 1 and 2

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Signed written informed consent for biological analysis (all pts)
• Signed written informed consent for enrolment (pts with KRAS wild type)
• Male or female aged > or = 18 years
• Diagnosis of histologically confirmed adenocarcinoma of the colon or rectum
• KRAS evaluation availability with wild-type result
• Metastatic CRC not suitable for curative-intent resection
• Availability of tumour samples (or able and willing to provide tumour sample) and blood for biological analysis
• Presence of at least one lesion measurable unidimensionally by computed tomography (CT) scan or magnetic resonance imaging (MRI). (index lesion(s) must not lie within an irradiated area)
• Eastern cooperative oncology group-performance status (ECOG-PS) <2

Exclusion Criteria

• Brain metastasis (known or suspected)
• Previous chemotherapy for metastatic CRC (any). Adjuvant therapy is allowed if the chemotherapy treatment free interval is > 6 months
• Surgery (excluding diagnostic biopsy) or irradiation within 4 weeks prior to study entry
• Concurrent chronic systemic immune therapy, chemotherapy, or hormone therapy not indicated in the study protocol
• Any investigational agent(s) within 4 weeks prior to entry
• Previous exposure to HER-axis -pathway targeting therapy
• Leucocytes <3.0 x 109/L and neutrophils <1.5 x 109/L, platelets <100 x 109/L, and hemoglobin <9 g/dL
• Bilirubin level either normal or >1.5 x ULN
• ASAT and ALAT >2.5 x ULN (>5 x ULN if liver metastasis are present)
• Serum creatinine >1.5 x ULN
• Clinically relevant coronary artery disease or a history of a myocardial infarction within the last 12 months
• Acute or sub-acute intestinal occlusion or history of inflammatory bowel disease
• Pre-existing neuropathy > grade 1
• Known grade 3 or 4 allergic reaction to any of the components of the treatment
• Any concurrent malignancy other than non-melanoma skin cancer, or carcinoma in situ of the cervix. (Pts with a previous malignancy but without evidence of disease for > or equal 5 years will be allowed to enter the trial)
• Pregnancy or lactation
• Inadequate contraception (male or female pts) if of childbearing or procreational potential
• Known drug abuse/ alcohol abuse
• Legal incapacity or limited legal capacity
• Medical or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or sign meaningful informed consent

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mario Negri Institute for Pharmacological Research

OTHER

Sponsor Role: collaborator

Istituto Clinico Humanitas

OTHER

Sponsor Role: collaborator

A.O. Ospedale Papa Giovanni XXIII

OTHER

Sponsor Role: collaborator

Regione Lombardia

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Roberto Labianca, MD

Role: PRINCIPAL_INVESTIGATOR

A.O. Ospedale Papa Giovanni XXIII

Armando Santoro, MD

Role: PRINCIPAL_INVESTIGATOR

Istituto Clinico Humanitas

Locations

Ospedali Riuniti di Bergamo

Bergamo, Bergamo, Italy

Ospedale di Treviglio e Caravaggio

Treviglio, Bergamo, Italy

IRCCS San Raffaele

Milan, Milano, Italy

Istututo Clinico Humanitas

Rozzano, Milano, Italy

Ospedale Morelli Sondalo

Sondalo, Sondrio, Italy

Ospedale di Sondrio

Sondrio, Sondrio, Italy

Ospedale di Saronno

Saronno, Varese, Italy

Countries

Italy

Other Identifiers

2008-007524-25

Identifier Type: -

Identifier Source: org_study_id