A Phase I and Pharmacokinetic Study of Oxaliplatin (Eloxatin™) in Combination With Bortezomib (PS-341, Velcade™) in Patients With Advanced Malignancy
I. Determine the maximum tolerated dose and recommended phase II dose of oxaliplatin and
bortezomib in patients with advanced malignancy.
II. Determine the dose-limiting toxicity of this regimen in these patients. III. Determine
the toxicity profile of this regimen in these patients. IV. Determine the antitumor activity
of this regimen in these patients. V. Determine the pattern of neurotoxicity and its
reversibility in patients responding to prolonged administration of this treatment regimen.
VI. Determine whether the pharmacokinetics and pharmacodynamics of oxaliplatin or bortezomib
are altered by the administration of the other agent in these patients.
OUTLINE: This is a dose-escalation study.
Patients receive oxaliplatin IV over 2 hours on days 1 and 15 and bortezomib IV over 3-5
seconds on days 1, 4, 15, and 18. Courses repeat every 28 days in the absence of disease
progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of oxaliplatin and bortezomib until the
maximum tolerated doses (MTDs) are determined. The MTD is defined as the dose preceding that
at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Patients are followed for at least 3 months.
PROJECTED ACCRUAL: A total of 15-30 patients will be accrued for this study within 4-15
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Probability of dose escalation according to true dose limiting toxicity (DLT) rate, based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0
Up to 28 days
Montefiore Medical Center
United States: Food and Drug Administration
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