Ixabepilone and Ketoconazole in Treating Patients With Advanced Solid Tumors

NCT ID: NCT00096317

Last Updated: 2018-10-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-03-31
• Study Completion Date: 2005-12-05

Brief Summary

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

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.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

ixabepilone

Intervention Type: DRUG

ketoconazole

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Montefiore Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sridhar Mani, MD

Role: STUDY_CHAIR

Albert Einstein College of Medicine

Locations

Albert Einstein Cancer Center at Albert Einstein College of Medicine

The Bronx, New York, United States

Countries

United States

References

Goel S, Cohen M, Comezoglu SN, Perrin L, Andre F, Jayabalan D, Iacono L, Comprelli A, Ly VT, Zhang D, Xu C, Humphreys WG, McDaid H, Goldberg G, Horwitz SB, Mani S. The effect of ketoconazole on the pharmacokinetics and pharmacodynamics of ixabepilone: a first in class epothilone B analogue in late-phase clinical development. Clin Cancer Res. 2008 May 1;14(9):2701-9. doi: 10.1158/1078-0432.CCR-07-4151.

Reference Type: RESULT

PMID: 18451235 (View on PubMed)

Other Identifiers

P30CA013330

Identifier Type: NIH

Identifier Source: secondary_id

View Link

AECM-03099

Identifier Type: -

Identifier Source: secondary_id

AECM-CA163402

Identifier Type: -

Identifier Source: secondary_id

AECM-NMC-03-10-277C

Identifier Type: -

Identifier Source: secondary_id

CDR0000393439

Identifier Type: -

Identifier Source: org_study_id