A Phase III Trial of Modified FOLFOX6 Versus CAPOX, With Bevacizumab (NSC-704865) or Placebo, as First-Line Therapy in Patients With Previously Untreated Advanced Colorectal Cancer
OBJECTIVES:
I. Compare overall survival in patients with locally advanced, metastatic, or recurrent
colorectal cancer treated with fluorouracil, leucovorin calcium, oxaliplatin, and
bevacizumab vs capecitabine, oxaliplatin, and bevacizumab.
II. Compare progression-free survival and time to treatment failure in patients treated with
these regimens.
III. Compare the response of patients with measurable disease treated with these regimens.
IV.Compare toxicity rates of these regimens in these patients. V. Compare patient-reported
functional status and convenience of therapy in patients treated with these regimens.
VI. Correlate germline polymorphisms of DNA repair (e.g., ERCC-1, XRCC1, GST-P1, XPD, and
ribonucleotide reductase), target enzymes (e.g., thymidylate synthase, dihydropyrimidine
dehydrogenase, and thymidine phosphorylase), angiogenesis (e.g., vascular endothelial growth
factor), and growth factors (e.g., epithelial growth factor receptor) with survival,
progression-free survival, and toxicity from chemotherapy in patients treated with these
regimens.
VII. Correlate tumor mRNA expression levels of similar DNA repair enzymes as well as enzymes
involved in angiogenesis with survival and progression-free survival in patients treated
with these regimens.Correlate tumor mRNA expression levels of similar target enzymes before
treatment with survival, progression-free survival, and toxicity in patients treated with
these regimens.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
Zubrod performance status (0 or 1 vs 2) and prior adjuvant therapy (yes vs no). Patients are
randomized to 1 of 2 treatment arms.
ARM I: Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours
on day 1 and fluorouracil IV continuously over 46-48 hours beginning on day 1. Patients are
further randomized to receive bevacizumab or placebo* IV over 30-90 minutes on day 1.
Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity.
NOTE: *As of 11/15/04, placebo is no longer part of treatment plan; all patients receive
bevacizumab.
ARM II: Patients receive oxaliplatin IV over 2 hours on day 1 and oral capecitabine on days
1-15. Patients are further randomized to receive bevacizumab or placebo* as in arm I.
Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
NOTE: *As of 11/15/04, placebo is no longer part of treatment plan; all patients receive
bevacizumab.
Patients are followed every 3 months until disease progression. After disease progression,
patients are followed every 6 months for 2 years and then annually for up to 4 years after
study entry.
PROJECTED ACCRUAL: A total of 2,200 patients (1,100 per treatment arm) will be accrued for
this study within 3 years.
Interventional
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Overall survival in patients with colorectal cancer treated with fluorouracil/leucovorin calcium and oxaliplatin with and without becavizumab versus those treated with capecitabine and oxaliplatin with our without bevacizumab
Will be analyzed primarily by the stratified Cox model.
Up to 6 years
No
Charles Blanke
Principal Investigator
Southwest Oncology Group
United States: Food and Drug Administration
NCI-2012-02556
NCT00070122
April 2004
Name | Location |
---|---|
Southwest Oncology Group | San Antonio, Texas 78245 |