Safety and Efficacy Study of Combination Therapy With Cetuximab and FOLFOX4 in Patients With Colorectal Cancer

Open-label, Phase II, Randomised, Pilot Study to Evaluate the Safety and Efficacy of Combination Therapy With Cetuximab and FOLFOX4 or FOLFOX4 Alone in Patients Colorectal Cancer and Initially Non-resectable

The purpose of this study is to determine confirmed objective response rate to combination therapy with cetuximab and FOLFOX4 or FOLFOX4 alone in patients with CRC and non-resectable hepatic metastases

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: FOLFOX-4+cetuximab; Drug: FOLFOX-4

• Study Type: Interventional
• Enrollment (Actual): 136
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28046
    • Spanish Cooperative Group for Gastrointestinal Tumour Therapy (TTD)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Written informed consent.
• Men and women < 75 years
• Histologically confirmed diagnosis of CRC

• Metastatic colorectal carcinoma with exclusive non-resectable hepatic metastases, due to fulfillment of one of the following criteria:

  1. Number of hepatic metastases > or= 4;
  2. Size of one or more hepatic metastases > 5 cm diameter;
  3. Vascular involvement and/or poor site that prevent complete resection of hepatic disease and/or require resection with the remaining liver mass less than 25-30% of functional liver.
• Presence of at least one lesion detectable by two-dimensional measurement.
• Karnofsky functional status >or=70% at the time of enrollment in study
• Life expectancy greater than 3 months.
• Patients must not have received chemotherapy for advanced/metastatic disease.

• Patients with the following characteristics will be enrolled:

  1. Recurrence after adjuvant treatment with 5-fluorouracil/folinic acid or capecitabine +/- radiotherapy with disease-free period > 6 months following conclusion of treatment.
  2. Recurrence after surgical and/or radiotherapy treatment without adjuvant systemic treatment.
  3. De novo diagnosis of disease.
• Proper liver function, defined by aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) < or = 2.5 x ULN (< or = 5 x ULN if there are hepatic metastases) and total bilirubin count < 1.5 x ULN.
• Proper kidney function, defined as serum creatinine < 1.5 x ULN.
• Proper hematological function, defined as neutrophil count > or = 1.5 x 109/l , platelets > or = 100 X 109/l and hemoglobin > or = 9 g/dl.
• Effective birth control method for men as well as women if there is possibility of pregnancy

Exclusion Criteria:

• Documented or suspected cerebral and/or leptomeningeal metastases.
• Metastasis in any other non-hepatic site, including extrahepatic lymph node metastases.
• Surgery (excluding biopsy for diagnosis) and/or radiotherapy within 4 weeks prior to enrollment in the study.
• Participation in another clinical trial with medication in the past 30 days.
• Chronic, concomitant administration of systemic immunotherapy, chemotherapy, hormone therapy or any other investigational drug.
• Prior malignant tumour in past 5 years, except history of basal cell skin carcinoma or pre-invasive cervical carcinoma.
• Any investigational drug during the 4 weeks prior to enrolment.
• Prior administration of monoclonal antibodies, EGFR signal transduction inhibitors or EGFR-targeted treatment.
• Prior participation in study in which treatment with cetuximab can be assigned (whether or not treatment with cetuximab is received)
• Acute or subacute intestinal occlusion or history of inflammatory intestinal disease.
• Evidence of grade 3 or 4 allergic reaction to any of the treatment components.
• Clinically relevant peripheral neuropathy.
• Clinically relevant myocardial disease or history of myocardial infarction in the past 12 months.
• Known abuse of alcohol / drugs, Legal incapacity or limited legal capacity.
• Any medical or psychological disorder which, in the opinion of the investigator, does not allow the patient to conclude the study or sign the informed consent.
• Pregnant or nursing woman

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; FOLFOX-4+cetuximab	Drug: FOLFOX-4+cetuximab; Cetuximab; Weekly administration of Cetuximab IV (initial infusion of 400 mg/m2 for 120 minutes followed by subsequent maintenance doses of 250 mg/m2 for 60 minutes); FOLFOX-4: Every two week Oxaliplatin; 85 mg/m2 ; day 1 Folinic acid; 200 mg/m2 ; day 1 and 2 5-FU ; Bolus 400 mg/m2 + CI 600 mg/m2 22 h day 1 and 2
Active Comparator: 2; FOLFOX-4	Drug: FOLFOX-4; FOLFOX-4: Every two week Oxaliplatin; 85 mg/m2 ; day 1 Folinic acid; 200 mg/m2 ; day 1 and 2 5-FU ; Bolus 400 mg/m2 + CI 600 mg/m2 22 h day 1 and 2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Determine confirmed objective response rate	2005-2009

Secondary Outcome Measures

Outcome Measure	Time Frame
Determine safety of combination, surgical resectability and R0 resections, clinical benefit, time to disease progression, time to onset of response, duration of response, time to treatment failure, overall survival time	2005-2009
determination of polymorphisms of the intron 1 of the EGFR gene, TS, XRCC1, XPD, serum levels of EGFR and ATP7A and ATP7B, nº of copies of EGFR gene, the levels of PTEN, EGFR, AKT y MAPK proteins, and mutations at EGFR, PI3KCA, K-RAS y B-RAF genes	2005-2009

Collaborators and Investigators

• Sponsor: Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Study Chair: Albert Abad, Spanish Cooperative Group for Gastrointestinal Tumour Therapy (TTD)

Study record dates

Study Major Dates

• Study Start: February 1, 2005
• Primary Completion (Actual): February 1, 2009
• Study Completion (Actual): February 1, 2009

Study Registration Dates

• First Submitted: September 12, 2005
• First Submitted That Met QC Criteria: September 12, 2005
• First Posted (Estimate): September 20, 2005

Study Record Updates

• Last Update Posted (Estimate): February 20, 2013
• Last Update Submitted That Met QC Criteria: February 19, 2013
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Keywords: colorectal cancer; cetuximab; FOLFOX4
• 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; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Antineoplastic Agents, Immunological; Micronutrients; Vitamins; Antidotes; Vitamin B Complex; Fluorouracil; Oxaliplatin; Leucovorin; Cetuximab
• Other Study ID Numbers: TTD-04-02; eudract-number: 2004-001700-12