A 2x2 Factorial Randomized Phase III Study of Intermittent Oral Capecitabine in Combination With Intravenous Oxaliplatin (Q3W) ("XELOX") With/Without Intravenous Bevacizumab (Q3W) Versus Bolus and Continuous Infusion Fluorouracil/Intravenous Leucovorin With Intravenous Oxaliplatin (Q2W) ("FOLFOX-4") With/Without Intravenous Bevacizumab (Q2W) as First-line Treatment for Patients With Metastatic Colorectal Cancer
18 Years
N/A
Both
Colorectal Cancer
Trial Information
A 2x2 Factorial Randomized Phase III Study of Intermittent Oral Capecitabine in Combination With Intravenous Oxaliplatin (Q3W) ("XELOX") With/Without Intravenous Bevacizumab (Q3W) Versus Bolus and Continuous Infusion Fluorouracil/Intravenous Leucovorin With Intravenous Oxaliplatin (Q2W) ("FOLFOX-4") With/Without Intravenous Bevacizumab (Q2W) as First-line Treatment for Patients With Metastatic Colorectal Cancer
This study was conducted in 2 parts: An initial 2-arm part in which patients were randomized
to 1 of 2 different treatment groups (XELOX or FOLFOX-4), and a subsequent 2 x 2 factorial
part, added to the study through a protocol amendment, in which additional patients were
randomized into one of 4 different treatment groups (XELOX + placebo, FOLFOX-4 + placebo,
XELOX + bevacizumab, or FOLFOX-4 + bevacizumab). Due to the comparison of the oral agent
capecitabine with bolus and infused fluorouracil, the study was not blinded with respect to
these 2 treatments. The study was double-blind with regard to the administration of
bevacizumab, ie, there was a placebo control for bevacizumab in the second part of the
study.
The study consisted of 3 phases, a Primary Study Treatment Phase, a Post-Study Treatment
Phase, and a Follow-Up Phase.
Primary Study Treatment Phase
Patients were to receive up to 16 cycles (2-arm part of the study) or 24 cycles (4-arm part
of the study) of treatment during the Primary Study Treatment Phase (48 weeks).
Post-Study Treatment Phase
Patients who completed the 48-week primary study treatment phase without progressive disease
were eligible to enter the post-study treatment phase at the discretion of the investigator
and the sponsor. Patients who entered this phase were to continue treatment on the same
regimen to which they were initially randomized until either progression of disease was
documented, unacceptable toxicity occurred, or the patient withdrew consent.
Follow-up Phase
Patients who terminated study treatment during the primary or post-study treatment phase
were followed until disease progression or death.
Inclusion Criteria:
- Adult patients ≥ 18 years of age.
- Metastatic colorectal cancer.
- ≥ 1 target lesion.
Exclusion Criteria:
- Previous treatment with oxaliplatin or bevacizumab.
- Previous systemic chemotherapy or immunotherapy for advanced or metastatic disease.
- Progressive disease during or within 6 months of completion of previous adjuvant
therapy.
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Outcome Measure:
Progression-free survival (PFS) as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST)
Outcome Description:
PFS was defined as the time from randomization to disease progression (PD) or death. All measurable lesions (maximum of 5 per organ and 10 in total, those with the longest diameter and suitability for accurate repeated measurements) were identified as target lesions (TL). A sum of the longest diameter for all TLs was calculated and reported as the baseline sum longest diameter(SLD). All other lesions were identified as non-TLs and recorded at baseline. PD for TLs was defined as ≥ 20% increase in the SLD, taking as reference the smallest SLD recorded since treatment started or the appearance of 1 or more new lesions. PD for non-TLs was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-TLs. Patients with neither PD nor death were censored at the date of the last tumor assessment that confirmed no PD. Patients who underwent surgical resection with curative intent without prior progression were censored at the date of surgery.
Outcome Time Frame:
Baseline to the 10 Feb 2005 data cut-off (up to 1 year 7 months)
Safety Issue:
No
Principal Investigator
Clinical Trials
Investigator Role:
Study Director
Investigator Affiliation:
Hoffmann-La Roche
Authority:
United States: Food and Drug Administration
Study ID:
NO16966
NCT ID:
NCT00069095
Start Date:
July 2003
Completion Date:
April 2009
Related Keywords:
- Colorectal Cancer
- Colorectal Neoplasms
Name | Location |
|---|---|
| Hinsdale, Illinois 60521 | |
| New Britain, Connecticut 06052 | |
| Alexandria, Minnesota 56308 | |
| Albany, Georgia 31701 | |
| Fountain Valley, California 92708 | |
| Miami, Florida 33176 | |
| Albany, New York 12208 | |
| Philadelphia, Pennsylvania 19104 | |
| Nashville, Tennessee 37203-1632 | |
| Austin, Texas 78705 | |
| Flint, Michigan 48532 | |
| Louisville, Kentucky 40207 | |
| McLean, Virginia 22101 | |
| Scarborough, Maine 04074 | |
| Hackensack, New Jersey 07601 | |
| Albuquerque, New Mexico 87131-5636 | |
| Metairie, Louisiana 70006 | |
| Boston, Massachusetts | |
| Charlotte, North Carolina | |
| South Burlington, Vermont | |
| Charleston, South Carolina | |
| Providence, Rhode Island 02908 | |
| Las Vegas, Nevada 89109 | |
| Bismarck, North Dakota 58501 |
