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