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Phase III Randomized Study of Leucovorin Calcium and Fluorouracil With or Without Oxaliplatin Versus Capecitabine With or Without Oxaliplatin in Patients With Metastatic Colorectal Adenocarcinoma
Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information
Alternate Title
Leucovorin and Fluorouracil With or Without Oxaliplatin Compared to Capecitabine With or Without Oxaliplatin in Treating Patients With Metastatic Colorectal Cancer
Basic Trial Information
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Protocol IDs
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Phase III
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Supportive care, Treatment
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Active
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Not specified
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Other
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NCRI-FOCUS2
MRC-CR09, EU-20303, NCT00070213
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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.
Entry Criteria 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
Prior/Concurrent Therapy:
Biologic therapy 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 Radiotherapy Surgery Other - No concurrent brivudine or sorivudine
Patient Characteristics:
Age Performance status Life expectancy Hematopoietic - WBC greater than 3,000/mm3
- Platelet count greater than 100,000/mm3
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
Expected Enrollment 460A total of 460 patients (115 per treatment arm) will be accrued for this study within 2 years. Outcomes Primary Outcome(s)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
Compare health assessment in patients treated with MdG vs Cap and in patients treated with OxMdG vs OxCap at baseline and 14 weeks
Secondary Outcome(s)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
Compare toxicity/adverse events in patients treated with MdG vs OxMdG and in patients treated with Cap vs OxCap
Compare overall failure-free survival in patients treated with MdG vs OxMdG and in patients treated with Cap vs OxCap
Compare overall survival in patients treated with MdG vs OxMdG and in patients treated with Cap vs OxCap
Compare health economics in patients treated with MdG vs OxMdG and in patients treated with Cap vs OxCap
Compare health assessment in patients treated with MdG vs Cap and in patients treated with OxMdG vs OxCap
Compare toxicity/adverse events in patients treated with MdG vs Cap and in patients treated with OxMdG vs OxCap at baseline and 24 weeks
Compare patients acceptability in patients treated with MdG vs Cap and in patients treated with OxMdG vs OxCap
Compare PFS in patients treated with MdG vs Cap and in patients treated with OxMdG vs OxCap
Compare health economics in patients treated with MdG vs Cap and in patients treated with OxMdG vs OxCap
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 Published ResultsSeymour 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.
Trial Contact Information
Trial Lead Organizations Clinical Trials and Research Unit of the University of Leeds | | | | Matthew Seymour, MA, MD, FRCP, Study coordinator | | | |
Medical Research Council Clinical Trials Unit | | | | Gareth Griffiths, Study coordinator | | | |
Trial Sites
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| United Kingdom |
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| England |
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Leeds |
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| | | | | Clinical Trials and Research Unit of the University of Leeds |
| | | Phil Quirke | |
| | | Cookridge Hospital |
| | | Matthew Seymour, MA, MD, FRCP | |
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London |
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| | | Medical Research Council Clinical Trials Unit |
| | | Gareth Griffiths | |
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| Wales |
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Cardiff |
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| | | | Velindre Cancer Center at Velindre Hospital |
| | | Alison Brewster, MD | |
| | | Timothy Maughan, MD | |
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| Registry Information | | | Official Title | | Drug Treatment for Bowel Cancer: Making the Best Choices When a Milder Treatment is Needed | | | Trial Start Date | | 2003-09-29 | | | Registered in ClinicalTrials.gov | | NCT00070213 | | | Date Submitted to PDQ | | 2003-08-14 | | | Information Last Verified | | 2007-08-03 |
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.  Back to Top |
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