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

Prognostic Factors for Patients With Advanced Colorectal Cancer Treated With Cetuximab. An Italian Trial

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.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: Cetuximab; Drug: FOLFIRI

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

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Bergamo, Italy, 24128
    • Ospedali Riuniti di Bergamo
  • Milano, Italy, 20132
    • IRCCS San Raffaele
  • Sondrio, Italy, 23100
    • Ospedale di Sondrio
  • Bergamo
    • Treviglio, Bergamo, Italy, 24047
      • Ospedale di Treviglio e Caravaggio
  • Milano
    • Rozzano, Milano, Italy, 20086
      • Istututo Clinico Humanitas
  • Sondrio
    • Sondalo, Sondrio, Italy, 23035
      • Ospedale Morelli Sondalo
  • Varese
    • Saronno, Varese, Italy, 21047
      • Ospedale di Saronno

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression free survival	untill 48 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival	untill 48 months

Collaborators and Investigators

• Sponsor: Regione Lombardia
• Collaborators: Mario Negri Institute for Pharmacological Research; Istituto Clinico Humanitas; A.O. Ospedale Papa Giovanni XXIII
• Investigators: Principal Investigator: Roberto Labianca, MD, A.O. Ospedale Papa Giovanni XXIII

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: May 4, 2009
• First Submitted That Met QC Criteria: February 11, 2010
• First Posted (Estimate): February 12, 2010

Study Record Updates

• Last Update Posted (Estimate): May 12, 2014
• Last Update Submitted That Met QC Criteria: May 9, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Keywords: Colorectal Neoplasms; KRAS; PTEN
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Cetuximab
• Other Study ID Numbers: 2008-007524-25