Leucovorin and Fluorouracil With or Without Oxaliplatin Compared to Capecitabine With or Without Oxaliplatin in Treating Patients With Metastatic Colorectal Cancer
- Conditions
- Colorectal Cancer
- Interventions
- Drug: FOLFOX regimenProcedure: quality-of-life assessment
- Registration Number
- NCT00070213
- Lead Sponsor
- Medical Research Council
- Brief Summary
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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 460
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description OxCap quality-of-life assessment - OxMdG (80%) for 12 weeks leucovorin calcium MdG + oxaliplatin OxMdG (80%) for 12 weeks oxaliplatin MdG + oxaliplatin MdG (modified de Gramont) quality-of-life assessment 2 weekly 5FU/FA schedule OxMdG (80%) for 12 weeks quality-of-life assessment MdG + oxaliplatin Capcitabine capecitabine - Capcitabine quality-of-life assessment - MdG (modified de Gramont) leucovorin calcium 2 weekly 5FU/FA schedule OxMdG (80%) for 12 weeks fluorouracil MdG + oxaliplatin MdG (modified de Gramont) FOLFOX regimen 2 weekly 5FU/FA schedule OxMdG (80%) for 12 weeks FOLFOX regimen MdG + oxaliplatin MdG (modified de Gramont) fluorouracil 2 weekly 5FU/FA schedule OxCap capecitabine - OxCap oxaliplatin -
- Primary Outcome Measures
Name Time Method 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 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 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
- Secondary Outcome Measures
Name Time Method 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 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 post 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 post 24 weeks Compare overall failure-free 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 Baseline, 14 and 24 weeks 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 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 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
Compare PFS 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
Compare overall 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
Compare patients acceptability in patients treated with MdG vs Cap and in patients treated with OxMdG vs OxCap post 24 weeks Compare patients acceptability 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 Baseline, 14 and 24 weeks Compare health economics in patients treated with MdG vs Cap and in patients treated with OxMdG vs OxCap
Trial Locations
- Locations (4)
Medical Research Council Clinical Trials Unit
š¬š§London, England, United Kingdom
Cookridge Hospital
š¬š§Leeds, England, United Kingdom
Clinical Trials and Research Unit of the University of Leeds
š¬š§Leeds, England, United Kingdom
Velindre Cancer Center at Velindre Hospital
š¬š§Cardiff, Wales, United Kingdom