Study to Evaluate the Efficacy and Safety of FOLFOX-4 Plus Cetuximab Versus UFOX Plus Cetuximab.

NCT ID: NCT00439517

Last Updated: 2014-06-27

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

302 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-02-28

Study Completion Date

2012-05-31

Brief Summary

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This is an exploratory study to compare activity and safety in 400 patients with previously untreated metastatic carcinoma of the colon treated with UFOX (a combination regimen of UFT® (Tegafur plus Uracil), Oxaliplatin, Folinic Acid) plus Cetuximab or FOLFOX-4 (a combination regimen of 5 Fluorouracil (5-FU), Oxaliplatin and Folinic Acid) plus Cetuximab)

Detailed Description

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Conditions

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Previously Untreated Metastatic Colorectal Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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1

UFOX + Cetuximab

Group Type EXPERIMENTAL

UFOX + Cetuximab

Intervention Type DRUG

* Cetuximab infusion (400 mg/m\^2 on day 1 of cycle 1 and 250 mg/m\^2 at each subsequent day 1, as well as on days 8, 15 and 22)
* Oxaliplatin infusion (85mg/m\^2) on days 1 and 15 (every 2 weeks)
* Oral UFT® (250mg/m\^2 tegafur + 560 mg/m\^2 uracil in 3 daily doses rounded to the nearest number of whole capsules) on days 1-21
* Oral Folinic Acid (90 mg in 3 daily divided doses) on days 1-21

2

FOLFOX4 + Cetuximab

Group Type ACTIVE_COMPARATOR

FOLFOX4 + Cetuximab

Intervention Type DRUG

* Cetuximab infusion (400 mg/m\^2 on day 1 of cycle 1 and 250 mg/m\^2 at each subsequent day 1, as well as on days 8, 15 and 22)
* Oxaliplatin infusion (85 mg/m\^2) on days 1 and 15 (every 2 weeks)
* 5-FU bolus + infusions (400 mg/m\^2) on days 1, 2, 15 and 16
* Folinic Acid infusions (200 mg/m\^2) on days 1, 2, 15 and 16

Interventions

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UFOX + Cetuximab

* Cetuximab infusion (400 mg/m\^2 on day 1 of cycle 1 and 250 mg/m\^2 at each subsequent day 1, as well as on days 8, 15 and 22)
* Oxaliplatin infusion (85mg/m\^2) on days 1 and 15 (every 2 weeks)
* Oral UFT® (250mg/m\^2 tegafur + 560 mg/m\^2 uracil in 3 daily doses rounded to the nearest number of whole capsules) on days 1-21
* Oral Folinic Acid (90 mg in 3 daily divided doses) on days 1-21

Intervention Type DRUG

FOLFOX4 + Cetuximab

* Cetuximab infusion (400 mg/m\^2 on day 1 of cycle 1 and 250 mg/m\^2 at each subsequent day 1, as well as on days 8, 15 and 22)
* Oxaliplatin infusion (85 mg/m\^2) on days 1 and 15 (every 2 weeks)
* 5-FU bolus + infusions (400 mg/m\^2) on days 1, 2, 15 and 16
* Folinic Acid infusions (200 mg/m\^2) on days 1, 2, 15 and 16

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Signed written informed consent
* Inpatient or outpatient ≥ 18 years of age
* Diagnosis of histologically confirmed adenocarcinoma of the colon or rectum
* First occurrence of metastatic disease (not curatively resectable)
* Presence of at least one lesion measurable uni dimensionally by computerised tomography (CT) scan or magnetic resonance imaging (MRI). (Target lesion(s) must not lie within an irradiated area)
* Life expectancy of ≥ 3 months
* Karnofsky performance status of ≥ 60, at study entry
* White blood cell count (WBC) ≥ 3 x 10\^9/L, with neutrophils ≥ 1.5 x 10\^9/L, platelets ≥ 100 x 10\^9/L, and hemoglobin ≥ 9 g/dL
* Aspartate transaminase and alanine transaminase ≤ 2.5 x Upper Limit of Normal (ULN) (≤ 5 x ULN if liver metastasis are present)
* Normal serum creatinine (in case of elevated creatinine, labelled ethylenediaminetetraacetic acid clearance ≥ 65 mL/min is acceptable)
* Effective contraception for both male and female subjects if the risk of conception exists
* Tumor biopsy or archived sample available

Exclusion Criteria

* Brain metastasis and/or leptomeningeal disease (known or suspected)
* Previous chemotherapy for colorectal cancer except adjuvant treatment with progression of disease documented \> 6 months after end of adjuvant treatment.
* Previous oxaliplatin-based chemotherapy
* Surgery (excluding diagnostic biopsy) or irradiation within 4 weeks prior to randomization
* Concurrent or previous chronic systemic immune therapy, targeted therapy, anti-vascular epithelial growth factor (VEGF) therapy, epidermal growth factor receptor (EGFR) pathway targeting therapy not indicated in the study protocol
* Concurrent hormonal therapy not indicated in the study protocol except for physiologic replacement or contraception
* Clinically relevant coronary artery disease, history of myocardial infarction in the last 12 months, or high risk of uncontrolled arrhythmia
* Peripheral neuropathy \>grade 1
* Known hypersensitivity reaction to any of the components of the treatment.
* Any concurrent malignancy other than basal cell cancer of the skin, or pre-invasive cancer of the cervix. (Subjects with a previous malignancy but without evidence of disease for ≥ 5 years will be allowed to enter the study)
* Pregnancy (absence to be confirmed by ß-human chorionic gonadotrophin test) or lactation period
* 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 subject to complete the study or sign meaningful informed consent
* Participation in another clinical study within the 30 days before randomization
* Significant disease which, in the investigator's opinion, would exclude the subject from the study
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jean-Yves Douillard, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Centre R Gauducheau

Locations

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Research Site

Buenos Aires, , Argentina

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Ciudad Autónoma Buenos Aires, , Argentina

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Perth, , Australia

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Wollongong, , Australia

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Graz, , Austria

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Vienna, , Austria

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Leuven, , Belgium

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Liège, , Belgium

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Belo Horizonte, , Brazil

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Cep Sao Paulo-SP, , Brazil

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Fortaleza, , Brazil

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Besançon, , France

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Caen, , France

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La Roche-sur-Yon, , France

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Lille, , France

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Marseille, , France

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Nice, , France

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Saint-Herblain, , France

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Strasbourg, , France

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Berlin, , Germany

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Dortmund, , Germany

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Dresden, , Germany

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Frankfurt am Main, , Germany

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Hamburg, , Germany

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Hanover, , Germany

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Heidelberg, , Germany

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Kassel, , Germany

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Krefeld, , Germany

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Magdeburg, , Germany

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München, , Germany

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Oldenburg, , Germany

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Wiesbaden, , Germany

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Dragana, , Greece

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Thessaloniki, , Greece

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Voútai, , Greece

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Hong Kong, , Hong Kong

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Shatin, , Hong Kong

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Haifa, , Israel

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Jerusalem, , Israel

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Benevento, , Italy

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Brescia, , Italy

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Cremona, , Italy

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Forlì, , Italy

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Padua, , Italy

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Pavia, , Italy

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Potenza, , Italy

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Reggio Emilia, , Italy

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Rimini, , Italy

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Roma, , Italy

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Sassari, , Italy

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Mexico City, , Mexico

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Krakow, , Poland

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Lublin, , Poland

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Opole, , Poland

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Warsaw, , Poland

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Bangkok, , Thailand

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Pathumwan, , Thailand

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Countries

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Argentina Australia Austria Belgium Brazil France Germany Greece Hong Kong Israel Italy Mexico Poland Thailand

References

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Douillard JY, Zemelka T, Fountzilas G, Barone C, Schlichting M, Heighway J, Eggleton SP, Srimuninnimit V. FOLFOX4 with cetuximab vs. UFOX with cetuximab as first-line therapy in metastatic colorectal cancer: The randomized phase II FUTURE study. Clin Colorectal Cancer. 2014 Mar;13(1):14-26.e1. doi: 10.1016/j.clcc.2013.11.009. Epub 2013 Nov 16.

Reference Type RESULT
PMID: 24370353 (View on PubMed)

Other Identifiers

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EMR200025-001

Identifier Type: -

Identifier Source: org_study_id

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