Phase I Trial of Bortezomib (NSC 681239, IND#58443) and Carboplatin in Recurrent or Progressive Epithelial Ovarian Cancer or Primary Peritoneal Cancer

OBJECTIVES:

• Determine the maximum tolerated dose of bortezomib in combination with carboplatin in patients with recurrent or progressive ovarian epithelial, primary peritoneal, or fallopian tube cancer.
• Determine the toxicity of this regimen in these patients.
• Determine the pharmacodynamics of this regimen in these patients by measurement of 20S proteasome inhibition in whole blood.
• Correlate toxicity with 20S proteasome inhibition in a whole blood assay in patients treated with this regimen.

OUTLINE: This is a dose-escalation study of bortezomib.

Patients receive carboplatin IV over 30 minutes on days 1 and 8 followed by 1 week of rest during the first course of treatment. Beginning with the second course, patients receive bortezomib IV on days 1, 4, 8, and 11 and carboplatin IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for up to 6 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 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 8 additional patients are accrued and treated at that dose.