Official Title: “Effect Of Ketoconazole On The Pharmacokinetics Of BMS-247550 In Patients With Advanced Cancer”

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.

Study Type: Interventional

Study Design: Treatment, Open Label

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.

Intervention(s) in this Clinical Trial

• Drug: ixabepilone
• Drug: ketoconazole

Primary Measures

• Effect of ketoconazole on the pharmacokinetics of ixabepilone
  • Safety Issue?: No

Secondary Measures

• Safety of ixabepilone with and without ketoconazole
  • Safety Issue?: Yes
• Antitumor activity
  • Safety Issue?: No

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 NOTE:
• *Baseline brain imaging is not required for patients with no signs or symptoms of brain metastasis

PATIENT CHARACTERISTICS:

• Age
• 18 and over
• Performance status
• 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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Albert Einstein College of Medicine of Yeshiva University

Overall Clinical Trial Officials and Contacts

Sridhar Mani, MD Study Chair Albert Einstein College of Medicine of Yeshiva University  

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00096317

Study ID Number: CDR0000393439

ClinicalTrials.gov Identifier: NCT00096317

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database