Ixabepilone and Ketoconazole in Treating Patients With Advanced Solid Tumors

OBJECTIVES:

Primary

• Determine the effect of ketoconazole on the pharmacokinetics of ixabepilone in patients with advanced solid tumors.

Secondary

• Determine the safety of ixabepilone when administered alone and in combination with ketoconazole in these patients.
• Determine, preliminarily, the antitumor activity of this regimen in these patients.

OUTLINE: This is an open-label, dose-escalation study of ixabepilone.

During course 1, patients receive oral ketoconazole on days 0-5 and ixabepilone IV over 3 hours on day 1. During course 2 and subsequent courses, patients receive only ixabepilone IV over 3 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of at least 3 patients receive escalating doses of ixabepilone during course 1 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 patients experience dose-limiting toxicity. At least 12 patients are treated at the MTD.

PROJECTED ACCRUAL: A total of 3-35 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed solid tumor
• Unresponsive to currently available therapy OR no known effective treatment exists
• Measurable or nonmeasurable disease
• Brain metastases allowed, provided the following criteria are met:

• Completed cranial radiotherapy at least 4 weeks ago
• Stable or reduced brain metastases by brain imaging*
• Clinically stable disease AND no steroid therapy within the past 2 weeks (Baseline brain imaging is not required for patients with no signs or symptoms of brain metastasis)

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Eastern Cooperative Oncology Group (ECOG) 0-1

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Not specified

Renal

• Not specified

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No more than 3 prior chemotherapy regimens
• No other concurrent chemotherapy (standard or investigational)

Endocrine therapy

• See Disease Characteristics

Radiotherapy

• See Disease Characteristics
• At least 3 weeks since prior radiotherapy and recovered
• No prior radiotherapy to > 25% of major bone-marrow containing areas (e.g., pelvis or lumbar spine)

Surgery

• At least 1 week since prior minor surgery and recovered
• At least 3 weeks since prior major surgery and recovered

Other

• More than 2 weeks since prior drugs that would inhibit or stimulate drug metabolism