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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00439517




Registration number
NCT00439517
Ethics application status
Date submitted
22/02/2007
Date registered
23/02/2007
Date last updated
27/06/2014

Titles & IDs
Public title
Study to Evaluate the Efficacy and Safety of FOLFOX-4 Plus Cetuximab Versus UFOX Plus Cetuximab.
Scientific 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.
Secondary ID [1] 0 0
EMR200025-001
Universal Trial Number (UTN)
Trial acronym
FUTURE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Previously Untreated Metastatic Colorectal Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - UFOX + Cetuximab
Treatment: Drugs - FOLFOX4 + Cetuximab

Experimental: 1 - UFOX + Cetuximab

Active Comparator: 2 - FOLFOX4 + Cetuximab


Treatment: Drugs: 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

Treatment: Drugs: 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 code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free Survival (PFS) - Duration from randomization until progression or death due to any cause. Only deaths within 12 weeks of last tumor assessment are considered. Patients without event are censored on the date of last tumor assessment. Response and progression were assessed by the Investigators using response evaluation criteria in solid tumors (RECIST) 1.0 criteria
Timepoint [1] 0 0
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 outcome [1] 0 0
Best Overall Response (BOR) - BOR defined as percentage of subjects, whose BOR was either (confirmed) complete response (CR) or partial response (PR), relative to the number of subjects belonging to the study population of interest. CR defined as "Disappearance of all target lesions plus disappearance of all non-target lesions & without appearance of any new lesions; confirmed minimum 4 weeks later. PR defined as "At least 30% reduction in the SOLD of target lesions plus no significant change in non-target lesions to qualify for either CR or PD without appearance of new lesions; confirmed minimum 4 weeks later
Timepoint [1] 0 0
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
Secondary outcome [2] 0 0
Overall Survival (OS) - Time from randomization to death. Patients without event are censored at the last date known to be alive or at the clinical cut-off date, whatever is earlier.
Timepoint [2] 0 0
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
Secondary outcome [3] 0 0
Overall Survival (OS) - Time from randomization to death. Patients without event are censored at the last date known to be alive or at the clinical cut-off date, whatever is earlier.
Timepoint [3] 0 0
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
Secondary outcome [4] 0 0
Quality of Life (QOL) Functional Assessment of Cancer Therapy-Colorectal (FACT-C) - All of the single-item measures of the FACT-C are assessed on ordinal response categories ranging from 0="Not at all" to 4="Very much". For scoring purposes the response scores are reversed on negatively phrased questions. The principle for scoring the sub-scales is the same in all cases: subscale score = (Sum of items × Number of items in the subscale) / numbers of items answered. The lowest possible total score is 0 and the highest is 136. A high scale score represents a high QOL.
Timepoint [4] 0 0
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
Secondary outcome [5] 0 0
QOL EuroQuol-5D (EQ-5D) Health Outcome Questionnaire - The EQ-5D questionnaire is a measure of health status that provides a simple descriptive profile and a single index value. The optional part of the questionnaire was not applied. The EQ-5D defines health in terms of mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The 5 items are combined to generate health profiles. These profiles were converted to a continuous single index score using a one to one matching. The lowest possible score is -0.59 and the highest is 1.00, higher scores on the EQ-5D represent a better QOL.
Timepoint [5] 0 0
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
Secondary outcome [6] 0 0
QOL Therapy Preference Questionnaire (TPQ) - TPQ was used to investigate which features of chemotherapy treatment are the most relevant in ensuring patient satisfaction. The most essential characteristics of a cancer medication are shown at baseline and at cycle 3, along with percentage of subjects selecting that characteristic.
Timepoint [6] 0 0
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
Secondary outcome [7] 0 0
Treatment Impact on Social Daily Living and Health Care Resource Utilization - Non-protocol medical care visits and consultations
Timepoint [7] 0 0
From randomisation until final visit, reported between day of first patient randomised, Feb 2007, until cut-off date, 30 Jun 2009
Secondary outcome [8] 0 0
Safety - Number of Patients Experiencing Any Adverse Event - Please refer to Adverse Events section for details of individual serious adverse events and other adverse events
Timepoint [8] 0 0
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

Eligibility
Key inclusion 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Perth
Recruitment hospital [2] 0 0
Research Site - Wollongong
Recruitment postcode(s) [1] 0 0
- Perth
Recruitment postcode(s) [2] 0 0
- Wollongong
Recruitment outside Australia
Country [1] 0 0
Argentina
State/province [1] 0 0
Buenos Aires
Country [2] 0 0
Argentina
State/province [2] 0 0
Ciudad Autónoma Buenos Aires
Country [3] 0 0
Austria
State/province [3] 0 0
Graz
Country [4] 0 0
Austria
State/province [4] 0 0
Wien
Country [5] 0 0
Belgium
State/province [5] 0 0
Leuven
Country [6] 0 0
Belgium
State/province [6] 0 0
Liège
Country [7] 0 0
Brazil
State/province [7] 0 0
Belo Horizonte
Country [8] 0 0
Brazil
State/province [8] 0 0
Cep Sao Paulo-SP
Country [9] 0 0
Brazil
State/province [9] 0 0
Fortaleza
Country [10] 0 0
France
State/province [10] 0 0
Besancon Cedex
Country [11] 0 0
France
State/province [11] 0 0
Caen-Cedex 5
Country [12] 0 0
France
State/province [12] 0 0
La Roche sur Yon
Country [13] 0 0
France
State/province [13] 0 0
Lille
Country [14] 0 0
France
State/province [14] 0 0
Marseille
Country [15] 0 0
France
State/province [15] 0 0
Nice
Country [16] 0 0
France
State/province [16] 0 0
Saint-Herblain
Country [17] 0 0
France
State/province [17] 0 0
Strasbourg
Country [18] 0 0
Germany
State/province [18] 0 0
Berlin
Country [19] 0 0
Germany
State/province [19] 0 0
Dortmund
Country [20] 0 0
Germany
State/province [20] 0 0
Dresden
Country [21] 0 0
Germany
State/province [21] 0 0
Frankfurt / Main
Country [22] 0 0
Germany
State/province [22] 0 0
Hamburg
Country [23] 0 0
Germany
State/province [23] 0 0
Hannover
Country [24] 0 0
Germany
State/province [24] 0 0
Heidelberg
Country [25] 0 0
Germany
State/province [25] 0 0
Kassel
Country [26] 0 0
Germany
State/province [26] 0 0
Krefeld
Country [27] 0 0
Germany
State/province [27] 0 0
Magdeburg
Country [28] 0 0
Germany
State/province [28] 0 0
München
Country [29] 0 0
Germany
State/province [29] 0 0
Oldenburg
Country [30] 0 0
Germany
State/province [30] 0 0
Wiesbaden
Country [31] 0 0
Greece
State/province [31] 0 0
Dragana
Country [32] 0 0
Greece
State/province [32] 0 0
Thessaloniki
Country [33] 0 0
Greece
State/province [33] 0 0
Voutes
Country [34] 0 0
Hong Kong
State/province [34] 0 0
Hong Kong
Country [35] 0 0
Hong Kong
State/province [35] 0 0
Sha Tin
Country [36] 0 0
Israel
State/province [36] 0 0
Haifa
Country [37] 0 0
Israel
State/province [37] 0 0
Jerusalem
Country [38] 0 0
Italy
State/province [38] 0 0
Benevento
Country [39] 0 0
Italy
State/province [39] 0 0
Brescia
Country [40] 0 0
Italy
State/province [40] 0 0
Cremona
Country [41] 0 0
Italy
State/province [41] 0 0
Forli
Country [42] 0 0
Italy
State/province [42] 0 0
Padova
Country [43] 0 0
Italy
State/province [43] 0 0
Pavia
Country [44] 0 0
Italy
State/province [44] 0 0
Potenza
Country [45] 0 0
Italy
State/province [45] 0 0
Reggio Emilia
Country [46] 0 0
Italy
State/province [46] 0 0
Rimini
Country [47] 0 0
Italy
State/province [47] 0 0
Roma
Country [48] 0 0
Italy
State/province [48] 0 0
Sassari
Country [49] 0 0
Mexico
State/province [49] 0 0
Mexico-City
Country [50] 0 0
Poland
State/province [50] 0 0
Krakow
Country [51] 0 0
Poland
State/province [51] 0 0
Lublin
Country [52] 0 0
Poland
State/province [52] 0 0
Opole
Country [53] 0 0
Poland
State/province [53] 0 0
Warsaw
Country [54] 0 0
Thailand
State/province [54] 0 0
Bangkok
Country [55] 0 0
Thailand
State/province [55] 0 0
Pathumwan

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Merck KGaA, Darmstadt, Germany
Address
Country

Ethics approval
Ethics application status

Summary
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)
Trial website
https://clinicaltrials.gov/show/NCT00439517
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Jean-Yves Douillard, MD PhD
Address 0 0
Centre R Gauducheau
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications