A Phase I Study Of PS-341 In Combination With Gemcitabine And Carbloplatin In Selected Stage IIIB Or IV Non-Small Cell Lung Cancer
I. Determine the safety and feasibility of combining bortezomib with gemcitabine and
carboplatin in patients with advanced or recurrent non-small cell lung cancer.
II. Determine the maximum tolerated dose of bortezomib administered in combination with
gemcitabine and carboplatin in these patients.
III. Correlate results from laboratory studies on patient tissue and serum specimens with
potential predictors of response in patients treated with this regimen.
IV. Determine, preliminarily, the response of patients treated with this regimen.
OUTLINE: This is a multicenter, dose-escalation study of bortezomib.
Patients receive gemcitabine IV over 30 minutes on days 1 and 8, carboplatin IV over 15-30
minutes on day 1, followed 1 hour later by bortezomib IV over 3-5 seconds on days 1, 4, 8,
and 11. Treatment repeats every 21 days for up to 6 courses in the absence of disease
progression or unacceptable toxicity. Patients with a clinical or radiographic response may
continue receiving bortezomib beyond 6 courses.
Cohorts of 3-6 patients receive escalating doses of bortezomib until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2
of 6 patients experience dose-limiting toxicity. Once the MTD is determined, at least 10
additional patients with chemotherapy-naive disease receive treatment as above with the MTD
Patients are followed for survival.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Toxicities at each dose level, graded using the CTC version 2.0
Summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity, (by NCI Common Toxicity Criteria and nadir or maximum values for the laboratory measures, time of onset (i.e. course number), duration, and reversibility or outcome. Tables will be created to summarize these toxicities and side effects by dose and course.
Beckman Research Institute
United States: Food and Drug Administration
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