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

NCT01068132 | Completed Phase 2 DMC

• 1 other identifier: 2008-007524-25
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 7

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.

Conditions

Colorectal Cancer

Keywords

Colorectal Neoplasms; KRAS; PTEN

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  untill 48 months

Secondary Outcomes (1)

• Overall survival

  untill 48 months

Study Arms (1)

1

EXPERIMENTAL

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; Drug: FOLFIRI

Interventions

Cetuximab DRUG

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

1

FOLFIRI 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

1

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Regione Lombardia: lead
• Mario Negri Institute for Pharmacological Research: collaborator
• Istituto Clinico Humanitas: collaborator
• A.O. Ospedale Papa Giovanni XXIII: collaborator

Study Sites (7)

Ospedali Riuniti di Bergamo

Bergamo, Bergamo, 24128, Italy

Location

Ospedale di Treviglio e Caravaggio

Treviglio, Bergamo, 24047, Italy

Location

IRCCS San Raffaele

Milan, Milano, 20132, Italy

Location

Istututo Clinico Humanitas

Rozzano, Milano, 20086, Italy

Location

Ospedale Morelli Sondalo

Sondalo, Sondrio, 23035, Italy

Location

Ospedale di Sondrio

Sondrio, Sondrio, 23100, Italy

Location

Ospedale di Saronno

Saronno, Varese, 21047, Italy

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Cetuximab; IFL protocol

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Roberto Labianca, MD

  A.O. Ospedale Papa Giovanni XXIII

  PRINCIPAL INVESTIGATOR

• Armando Santoro, MD

  Istituto Clinico Humanitas

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2009
• First Posted: February 12, 2010
• Study Start: April 1, 2009
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: May 12, 2014

Record last verified: 2014-05

Locations

IT (7)