Bortezomib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Phase I trial to study the effectiveness of combining bortezomib with carboplatin and etoposide in treating patients who have advanced solid tumors that have not responded to previous treatment
PRIMARY OBJECTIVES: I. Determine the maximum tolerated dose (MTD) of bortezomib, carboplatin, and etoposide in patients with advanced solid tumors refractory to standard therapy. II. Evaluate biologic effects of bortezomib on relevant targets in the tumor tissues of patients treated with this regimen. OUTLINE: This is a dose-escalation study of bortezomib, etoposide, and carboplatin. Patients receive bortezomib IV on days 1 and 8, carboplatin IV over 30 minutes on day 1, and etoposide IV over 60 minutes on days 1-3. Treatment repeats every 21 days for at least 2 courses in the absence of disease progression or unacceptable toxicity. 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 or more of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 6 additional patients with newly diagnosed, chemotherapy-naive extensive stage small cell lung cancer, and 6 patients with other tumor types, are treated at that dose. PROJECTED ACCRUAL: A total of 12-27 patients will be accrued for this study within 6-14 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
27
University of Colorado
Denver, Colorado, United States
MTD defined as the dose level below the dose level that results in DLT in >= 2 of 6 new patients assessed using NCI CTC version 2.0
Time frame: 21 days
Biological data
The variation of these samples as a function of dose and time will be analyzed to define the mathematical function (e.g. linear, exponential, logistic) that best fits and models the data.
Time frame: Up to 4 years
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Correlative studies
Correlative studies