Ixabepilone and Ketoconazole in Treating Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as ixabepilone and ketoconazole, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving ixabepilone with ketoconazole may kill more tumor cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of giving ixabepilone together with ketoconazole and to see how well they work in treating patients with advanced solid tumors.

Detailed Description
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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.

Official Title
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The Effect of Ketoconazole on the Pharmacokinetics and Pharmacodynamics of Ixabepilone In Patients With Advanced Cancer

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: ixabepilone
* Drug: ketoconazole


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: ixabepilone|nan|
|Drug: ketoconazole|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of ketoconazole on the pharmacokinetics of ixabepilone |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of ixabepilone with and without ketoconazole |  |  | 
| Antitumor activity |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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unspecified adult solid tumor, protocol specific