- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00070213
Leucovorin and Fluorouracil With or Without Oxaliplatin Compared to Capecitabine With or Without Oxaliplatin in Treating Patients With Metastatic Colorectal Cancer
Drug Treatment for Bowel Cancer: Making the Best Choices When a Milder Treatment is Needed
RATIONALE: Drugs used in chemotherapy, such as leucovorin, fluorouracil, capecitabine, and oxaliplatin, use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known whether leucovorin and fluorouracil with or without oxaliplatin is more effective than capecitabine with or without oxaliplatin in treating patients who have metastatic colorectal cancer.
PURPOSE: This randomized phase III trial is studying four different chemotherapy regimens to compare how well they work in treating patients with metastatic colorectal cancer.
Study Overview
Status
Conditions
Detailed Description
OBJECTIVES:
Primary
- Compare the progression-free survival of patients with metastatic colorectal adenocarcinoma treated with leucovorin calcium and fluorouracil with vs without oxaliplatin or capecitabine with vs without oxaliplatin.
- Compare the quality of life of patients treated with these fluorouracil-based vs capecitabine-based regimens.
Secondary
- Compare the failure-free and overall survival of patients treated with these regimens.
- Compare the toxic effects and adverse events associated with these regimens in these patients.
- Compare the limited health assessments of patients treated with these regimens.
- Compare the health economics associated with these regimens.
OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 4 treatment arms and receive 12 weeks of therapy.
- Arm I (MdG regimen): Patients receive leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV over 46 hours beginning on day 1. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Patients with disease progression during or within 8 weeks of the completion of this regimen may cross over and receive second-line therapy on arm II.
- Arm II (OxMdG regimen): Patients receive leucovorin calcium IV over 2 hours and oxaliplatin IV over 2 hours on day 1 and fluorouracil IV over 46 hours beginning on day 1. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Patients with disease progression during or within 8 weeks of the completion of this regimen may receive second-line therapy or supportive care off-study.
- Arm III (Cap regimen): Patients receive oral capecitabine twice daily on days 1-15. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Patients with disease progression during or within 8 weeks of the completion of this regimen may cross over and receive second-line therapy on arm IV.
- Arm IV (OxCap regimen): Patients receive oxaliplatin IV over 2 hours on day 1 and oral capecitabine twice daily on days 1-15. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Patients with disease progression during or within 8 weeks of the completion of this regimen may receive second-line therapy or supportive care off-study.
All patients are then re-evaluated at least every 6 weeks and begin another 12 weeks of therapy at any evidence (e.g., clinical, radiological, or tumor marker) of disease progression. Patients with chemo-sensitive disease may repeat alternating 12-week therapy sessions and evaluation periods indefinitely.
Quality of life is assessed at baseline, at 12-14 weeks, at 24 weeks, and then every 3 months thereafter.
Patients are followed every 3 months.
Peer Reviewed and Funded or Endorsed by Cancer Research UK
PROJECTED ACCRUAL: A total of 460 patients (115 per treatment arm) will be accrued for this study within 2 years.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
England
-
Leeds, England, United Kingdom, LS16 6QB
- Cookridge Hospital
-
Leeds, England, United Kingdom, LS2 9JT
- Clinical Trials and Research Unit of the University of Leeds
-
London, England, United Kingdom, NW1 2DA
- Medical Research Council Clinical Trials Unit
-
-
Wales
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Cardiff, Wales, United Kingdom, CF14 2TL
- Velindre Cancer Center at Velindre Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
DISEASE CHARACTERISTICS:
Diagnosis of colorectal adenocarcinoma, defined by 1 of the following:
- Prior or current histologically confirmed primary adenocarcinoma of the colon or rectum with clinical/radiological evidence of advanced/metastatic disease
- Histologically or cytologically confirmed metastatic adenocarcinoma with clinical/radiological evidence of colorectal primary tumor
- Unidimensionally measurable disease
Unfit and unsuitable for full-dose combination chemotherapy, which would include 1 of the following circumstances:
- Unsuitable or unwilling to be entered into any full-dose chemotherapy protocol
- Ineligible or unsuitable for first-line standard combination as per National Institute of Clinical Excellence guidance
PATIENT CHARACTERISTICS:
Age
- Not specified
Performance status
- WHO 0-2
Life expectancy
- Not specified
Hematopoietic
- WBC greater than 3,000/mm^3
- Platelet count greater than 100,000/mm^3
Hepatic
- Bilirubin no greater than 3 times upper limit of normal (ULN)
- AST or ALT no greater than 2.5 times ULN
Renal
- Creatinine clearance greater than 50 mL/min OR
- Glomerular filtration rate greater than 30 mL/min
Cardiovascular
- No uncontrolled angina
- No recent myocardial infarction
Other
- Not pregnant
- Negative pregnancy test
- Fertile patients must use effective contraception
- No partial or complete bowel obstruction
- No concurrent severe uncontrolled medical illness that would preclude study treatment
- No psychiatric or neurological condition that would preclude giving informed consent or complying with oral study medication
- No other prior or concurrent malignant disease that would preclude study treatment or assessment of response
- No prior neuropathy greater than grade 1
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
- More than 4 months since prior adjuvant chemotherapy with fluorouracil with or without leucovorin calcium
- More than 1 month since prior rectal chemoradiotherapy with fluorouracil with or without leucovorin calcium
- No prior systemic palliative chemotherapy for metastatic disease
Endocrine therapy
- Not specified
Radiotherapy
- See Chemotherapy
Surgery
- Not specified
Other
- No concurrent brivudine or sorivudine
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: SINGLE_GROUP
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
ACTIVE_COMPARATOR: MdG (modified de Gramont)
2 weekly 5FU/FA schedule
|
|
EXPERIMENTAL: OxMdG (80%) for 12 weeks
MdG + oxaliplatin
|
|
EXPERIMENTAL: Capcitabine
|
|
EXPERIMENTAL: OxCap
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Compare progression-free survival (PFS) in pts. treated w/ leucovorin calcium + fluorouracil (MdG) vs leucovorin calcium + fluorouracil + oxaliplatin (OxMdG) and in pts. treated w/ capecitabine (Cap) vs capecitabine + oxaliplatin (OxCap) at 1 yr
Time Frame: PFS
|
Compare progression-free survival (PFS) in pts.
treated w/ leucovorin calcium + fluorouracil (MdG) vs leucovorin calcium + fluorouracil + oxaliplatin (OxMdG) and in pts.
treated w/ capecitabine (Cap) vs capecitabine + oxaliplatin (OxCap) at 1 yr
|
PFS
|
Compare health assessment in patients treated with MdG vs Cap and in patients treated with OxMdG vs OxCap at baseline and 14 weeks
Time Frame: Baseline and 14 weeks
|
Compare health assessment in patients treated with MdG vs Cap and in patients treated with OxMdG vs OxCap at baseline and 14 weeks
|
Baseline and 14 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Compare health assessment, including quality of life, in patients treated with MdG vs OxMdG and in patients treated with Cap vs OxCap at baseline and 14 and 24 weeks
Time Frame: Baseline, 14 and 24 weeks
|
Compare health assessment, including quality of life, in patients treated with MdG vs OxMdG and in patients treated with Cap vs OxCap at baseline and 14 and 24 weeks
|
Baseline, 14 and 24 weeks
|
Compare toxicity/adverse events in patients treated with MdG vs OxMdG and in patients treated with Cap vs OxCap
Time Frame: post 24 weeks
|
Compare toxicity/adverse events in patients treated with MdG vs OxMdG and in patients treated with Cap vs OxCap
|
post 24 weeks
|
Compare overall failure-free survival in patients treated with MdG vs OxMdG and in patients treated with Cap vs OxCap
Time Frame: post 24 weeks
|
Compare overall failure-free survival in patients treated with MdG vs OxMdG and in patients treated with Cap vs OxCap
|
post 24 weeks
|
Compare overall survival in patients treated with MdG vs OxMdG and in patients treated with Cap vs OxCap
Time Frame: post 24 weeks
|
Compare overall survival in patients treated with MdG vs OxMdG and in patients treated with Cap vs OxCap
|
post 24 weeks
|
Compare health economics in patients treated with MdG vs OxMdG and in patients treated with Cap vs OxCap
Time Frame: Baseline, 14 and 24 weeks
|
Compare health economics in patients treated with MdG vs OxMdG and in patients treated with Cap vs OxCap
|
Baseline, 14 and 24 weeks
|
Compare health assessment in patients treated with MdG vs Cap and in patients treated with OxMdG vs OxCap
Time Frame: Baseline, 14 and 24 weeks
|
Baseline, 14 and 24 weeks
|
|
Compare toxicity/adverse events in patients treated with MdG vs Cap and in patients treated with OxMdG vs OxCap at baseline and 24 weeks
Time Frame: Baseline and 24 weeks
|
Compare toxicity/adverse events in patients treated with MdG vs Cap and in patients treated with OxMdG vs OxCap at baseline and 24 weeks
|
Baseline and 24 weeks
|
Compare patients acceptability in patients treated with MdG vs Cap and in patients treated with OxMdG vs OxCap
Time Frame: post 24 weeks
|
Compare patients acceptability in patients treated with MdG vs Cap and in patients treated with OxMdG vs OxCap
|
post 24 weeks
|
Compare PFS in patients treated with MdG vs Cap and in patients treated with OxMdG vs OxCap
Time Frame: post 24 weeks
|
Compare PFS in patients treated with MdG vs Cap and in patients treated with OxMdG vs OxCap
|
post 24 weeks
|
Compare health economics in patients treated with MdG vs Cap and in patients treated with OxMdG vs OxCap
Time Frame: Baseline, 14 and 24 weeks
|
Compare health economics in patients treated with MdG vs Cap and in patients treated with OxMdG vs OxCap
|
Baseline, 14 and 24 weeks
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Matthew T. Seymour, MA, MD, FRCP, Cookridge Hospital
- Study Chair: Gareth Griffiths, Medical Research Council
Publications and helpful links
General Publications
- Seymour MT, Thompson LC, Wasan HS, Middleton G, Brewster AE, Shepherd SF, O'Mahony MS, Maughan TS, Parmar M, Langley RE; FOCUS2 Investigators; National Cancer Research Institute Colorectal Cancer Clinical Studies Group. Chemotherapy options in elderly and frail patients with metastatic colorectal cancer (MRC FOCUS2): an open-label, randomised factorial trial. Lancet. 2011 May 21;377(9779):1749-59. doi: 10.1016/S0140-6736(11)60399-1. Epub 2011 May 11.
- Seymour MT, Maughan TS, Wasan HS, et al.: Capecitabine (Cap) and oxaliplatin (Ox) in elderly and/or frail patients with metastatic colorectal cancer: the FOCUS2 trial. [Abstract] J Clin Oncol 25 (Suppl 18): A-9030, 500s, 2007.
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
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
- Micronutrients
- Vitamins
- Calcium-Regulating Hormones and Agents
- Antidotes
- Vitamin B Complex
- Fluorouracil
- Capecitabine
- Oxaliplatin
- Leucovorin
- Calcium
- Levoleucovorin
Other Study ID Numbers
- CDR0000330142
- NCRI-FOCUS2
- MRC-CR09
- EU-20303
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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