A Phase 1 Study of PS-341 in Combination With Docetaxel in Patients With Advanced Solid Tumors
I. Determine the maximum tolerated dose of bortezomib and docetaxel in patients with
advanced solid tumors.
II. Determine the toxicity and tolerability of this regimen in these patients. III.
Determine the biologic correlates of proteasome inhibition of bortezomib and determine the
effects of this inhibition on the pharmacokinetics of docetaxel in these patients.
IV. Determine the antitumor efficacy of this regimen in these patients.
OUTLINE: This is a dose-escalation study.
For course 1, patients receive docetaxel IV over 1 hour on days 1 and 8 and bortezomib IV
over 3-5 seconds on days 9 and 12. Patients then receive 1 week of rest. For course 2 and
all subsequent courses, patients receive docetaxel on days 1 and 8 and bortezomib on days 2,
5, 9, and 12. Courses repeat every 3 weeks in the absence of disease progression or
unacceptable toxicity. Cohorts of 2-6 patients receive escalating doses of bortezomib and
docetaxel until the maximum tolerated dose (MTD) is determined. The MTD is defined as the
dose at which no more than 1 of 6 patients experiences dose-limiting toxicity.
PROJECTED ACCRUAL: A minimum of 24 patients will be accrued for this study.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum-tolerated dose (MTD) based on the incidence of dose-limiting toxicity (DLT) as assessed by the NCI Common Toxicity Criteria (CTC) version 2.0
Johns Hopkins University
United States: Food and Drug Administration
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