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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00439517
Recruitment Status : Completed
First Posted : February 23, 2007
Results First Posted : June 14, 2011
Last Update Posted : June 27, 2014
Sponsor:
Information provided by (Responsible Party):
Merck KGaA, Darmstadt, Germany

Tracking Information
First Submitted Date  ICMJE February 22, 2007
First Posted Date  ICMJE February 23, 2007
Results First Submitted Date  ICMJE March 31, 2011
Results First Posted Date  ICMJE June 14, 2011
Last Update Posted Date June 27, 2014
Study Start Date  ICMJE February 2007
Actual Primary Completion Date June 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 14, 2013)
Progression-free Survival (PFS) [ Time Frame: 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 ]
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
Original Primary Outcome Measures  ICMJE
 (submitted: February 22, 2007)
Progression free survival
Change History Complete list of historical versions of study NCT00439517 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 14, 2013)
  • Best Overall Response (BOR) [ Time Frame: 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 ]
    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
  • Overall Survival (OS) [ Time Frame: 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 ]
    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.
  • Overall Survival (OS) [ Time Frame: 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 ]
    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.
  • Quality of Life (QOL) Functional Assessment of Cancer Therapy-Colorectal (FACT-C) [ Time Frame: 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 ]
    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.
  • QOL EuroQuol-5D (EQ-5D) Health Outcome Questionnaire [ Time Frame: 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 ]
    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.
  • QOL Therapy Preference Questionnaire (TPQ) [ Time Frame: 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 ]
    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.
  • Treatment Impact on Social Daily Living and Health Care Resource Utilization [ Time Frame: From randomisation until final visit, reported between day of first patient randomised, Feb 2007, until cut-off date, 30 Jun 2009 ]
    Non-protocol medical care visits and consultations
  • Safety - Number of Patients Experiencing Any Adverse Event [ Time Frame: 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 ]
    Please refer to Adverse Events section for details of individual serious adverse events and other adverse events
Original Secondary Outcome Measures  ICMJE
 (submitted: February 22, 2007)
  • Response rate (CR and PR) in each are
  • Overall survival (OS) in each arm
  • Safety
  • Quality of Life (QOL) (FACT-C, EQ-5D and Patient Satisfaction Questionnaire)
  • Treatment Impact on Social Daily Living and Health Care Resource Utilization
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Evaluate the Efficacy and Safety of FOLFOX-4 Plus Cetuximab Versus UFOX Plus Cetuximab.
Official Title  ICMJE 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.
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)
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Previously Untreated Metastatic Colorectal Cancer
Intervention  ICMJE
  • Drug: 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
  • 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
Study Arms  ICMJE
  • Experimental: 1
    UFOX + Cetuximab
    Intervention: Drug: UFOX + Cetuximab
  • Active Comparator: 2
    FOLFOX4 + Cetuximab
    Intervention: Drug: FOLFOX4 + Cetuximab
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 13, 2011)
302
Original Enrollment  ICMJE
 (submitted: February 22, 2007)
400
Actual Study Completion Date  ICMJE May 2012
Actual Primary Completion Date June 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Austria,   Belgium,   Brazil,   France,   Germany,   Greece,   Hong Kong,   Israel,   Italy,   Mexico,   Poland,   Thailand
Removed Location Countries Portugal,   United Kingdom
 
Administrative Information
NCT Number  ICMJE NCT00439517
Other Study ID Numbers  ICMJE EMR200025-001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Merck KGaA, Darmstadt, Germany
Study Sponsor  ICMJE Merck KGaA, Darmstadt, Germany
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jean-Yves Douillard, MD PhD Centre R Gauducheau
PRS Account Merck KGaA, Darmstadt, Germany
Verification Date June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP