Clinical trial NCT00439517: Study to Evaluate the Efficacy and Safety of FOLFOX-4 Plus Cetuximab Versus UFOX Plus Cetuximab.
Official title: A Randomized, Open-label Phase II Study Evaluating the Efficacy and Safety of FOLFOX-4 Plus Cetuximab Versus UFOX Plus Cetuximab as First-line Therapy in Subjects With Metastatic Colorectal Cancer.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Previously Untreated Metastatic Colorectal Cancer
Keywords: Cancer
Colorectal
Metastatic
Untreated
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2007-02-23
Enrollment: 302
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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)


Eligibility criteria: 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

Primary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: Time from randomization to disease progression, death, or last tumor assessment reported between day of first patient randomised, Feb 2007, until cut off date, 30 Jun 2009
Secondary outcomes:
measure: Best Overall Response (BOR)
timeFrame: Evaluations were performed every 8 weeks until disease progression, reported between day of first patient randomised, Feb 2007, until cut off date, 30 Jun 2009
measure: Overall Survival (OS)
timeFrame: Time from randomization to death or last known to be alive, reported between day of first patient randomised, Feb 2007, until cut off date, 30 Jun 2009
measure: Overall Survival (OS)
timeFrame: Time from randomization to death or last known to be alive, reported between day of first patient randomised, Feb 2007, until cut off date, 31 Aug 2011
measure: Quality of Life (QOL) Functional Assessment of Cancer Therapy-Colorectal (FACT-C)
timeFrame: At baseline, at every first day of every third cycle during active - treatment, and at final tumor assessment , reported between day of first patient randomised, Feb 2007, until cut-off date, 30 Jun 2009. Cycles were 4 weeks long unless dosing delays
measure: QOL EuroQuol-5D (EQ-5D) Health Outcome Questionnaire
timeFrame: at baseline, at every first day of every third cycle during active - treatment, and at final tumor assessment , reported between day of first patient randomised, Feb 2007, until cut-off date, 30 Jun 2009. All cycles were 4 weeks long unless dosing delays
measure: QOL Therapy Preference Questionnaire (TPQ)
timeFrame: at baseline, at every first day of every third cycle during active - treatment, and at final tumor assessment , reported between day of first patient randomised, Feb 2007, until cut-off date, 30 Jun 2009. All cycles were 4 weeks long unless dosing delays
measure: Treatment Impact on Social Daily Living and Health Care Resource Utilization
timeFrame: From randomisation until final visit, reported between day of first patient randomised, Feb 2007, until cut-off date, 30 Jun 2009
measure: Safety - Number of Patients Experiencing Any Adverse Event
timeFrame: Time from first dose up to 30 days after last dose of study treatment, reported between day of first patient randomised, Feb 2007, until cut off date, 30 Jun 2009
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
facility: Research Site
city: Ciudad Autónoma Buenos Aires
country: Argentina
facility: Research Site
city: Perth
country: Australia
facility: Research Site
city: Wollongong
country: Australia
facility: Research Site
city: Graz
country: Austria
facility: Research Site
city: Wien
country: Austria
facility: Research Site
city: Leuven
country: Belgium
facility: Research Site
city: Liège
country: Belgium
facility: Research Site
city: Belo Horizonte
country: Brazil
facility: Research Site
city: Cep Sao Paulo-SP
country: Brazil
facility: Research site
city: Fortaleza
country: Brazil
facility: Research Site
city: Besancon Cedex
country: France
facility: Research Site
city: Caen-Cedex 5
country: France
facility: Research Site
city: La Roche sur Yon
country: France
facility: Research Site
city: Lille
country: France
facility: Research Site
city: Marseille
country: France
facility: Research Site
city: Nice
country: France
facility: Research Site
city: Saint-Herblain
country: France
facility: Research Site
city: Strasbourg
country: France
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Dortmund
country: Germany
facility: Research Site
city: Dresden
country: Germany
facility: Research Site
city: Frankfurt / Main
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Hannover
country: Germany
facility: Research Site
city: Heidelberg
country: Germany
facility: Research Site
city: Kassel
country: Germany
facility: Research Site
city: Krefeld
country: Germany
facility: Research Site
city: Magdeburg
country: Germany
facility: Research Site
city: München
country: Germany
facility: Research Site
city: Oldenburg
country: Germany
facility: Research Site
city: Wiesbaden
country: Germany
facility: Research Site
city: Dragana
country: Greece
facility: Research Site
city: Thessaloniki
country: Greece
facility: Research Site
city: Voutes
country: Greece
facility: Research Site
city: Hong Kong
country: Hong Kong
facility: Research Site
city: Sha Tin
country: Hong Kong
facility: Research Site
city: Haifa
country: Israel
facility: Research Site
city: Jerusalem
country: Israel
facility: Research Site
city: Benevento
country: Italy
facility: Research Site
city: Brescia
country: Italy
facility: Research Site
city: Cremona
country: Italy
facility: Research Site
city: Forli
country: Italy
facility: Research Site
city: Padova
country: Italy
facility: Research Site
city: Pavia
country: Italy
facility: Research Site
city: Potenza
country: Italy
facility: Research Site
city: Reggio Emilia
country: Italy
facility: Research Site
city: Rimini
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Sassari
country: Italy
facility: Research Site
city: Mexico-City
country: Mexico
facility: Research Site
city: Krakow
country: Poland
facility: Research Site
city: Lublin
country: Poland
facility: Research Site
city: Opole
country: Poland
facility: Research Site
city: Warsaw
country: Poland
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Pathumwan
country: Thailand
facility: Research Site
Study officials:
affiliation: Centre R Gauducheau
name: Jean-Yves Douillard, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.