Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Ixabepilone in Treating Patients With Recurrent Glioma

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II, Phase I Treatment Completed 18 and over NCI NABTT-2111 JHOC-NABTT-2111, NCT00045708

Objectives

1. Determine the maximum tolerated dose of ixabepilone in patients with recurrent high-grade glioma who are receiving or not receiving cytochrome P450-inducing anticonvulsants.
2. Determine the pharmacokinetics of this drug in these patients.
3. Determine the response rate of patients treated with this drug.
4. Determine the toxicity of this drug in these patients.
5. Determine the 6-month progression-free survival, duration of progression-free survival, and overall survival of patients treated with this drug.

Entry Criteria

Disease Characteristics:

• Histologically confirmed malignant glioma
  • Anaplastic astrocytoma, glioblastoma multiforme, anaplastic oligodendroglioma, or anaplastic mixed glioma
  • Recurrent or progressive after radiotherapy with or without chemotherapy
  • Prior low-grade glioma that has progressed to high-grade glioma allowed



• Measurable disease by MRI or CT scan

Prior/Concurrent Therapy:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics
• No more than 2 prior chemotherapy regimens
• At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas)

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• At least 3 months since prior radiotherapy

Surgery

• Not specified

Other

• Recovered from prior therapy
• No other concurrent investigational agents
• No concurrent moderate to significant inhibitors of CYP3A4, including any of the following:
  • Clarithromycin
  • Erythromycin
  • Troleandomycin
  • Delaviridine
  • Nelfinavir
  • Amprenavir
  • Ritonavir
  • Indinavir
  • Saquinavir
  • Lopinavir
  • Itraconazole
  • Ketoconazole
  • Fluconazole (doses > 200 mg/day)
  • Voriconazole
  • Verapamil
  • Diltiazem
  • Amiodarone
  • Nefazodone
  • Fluoroxamine

Patient Characteristics:

Age

• 18 and over

Performance status

• Karnofsky 60-100%

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³
• Hemoglobin greater than 9 g/dL

Hepatic

• Bilirubin no greater than 1.5 mg/dL
• AST/ALT no greater than 2.5 times upper limit of normal

Renal

• Creatinine no greater than 1.5 mg/dL

Other

• Mini mental score at least 15
• No other malignancy within the past 5 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast
• No concurrent serious infection or medical illness that would preclude study therapy
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

Expected Enrollment

A minimum of 10-15 patients will be accrued for the phase I portion of this study. A total of 22-33 patients will be accrued for the phase II portion of this study within 4-6 months.

Outcomes

Maximum tolerated dose
Pharmacokinetics
Response rate
Toxicity
Progression-free survival at 6 months
Duration of progression-free survival
Overall survival

Outline

This is a phase I, dose-escalation, multicenter study followed by a phase II, safety and efficacy, multicenter study. For phase I only, patients are stratified according to cytochrome P450-inducing anticonvulsant use (yes vs no).

• Phase I: Patients receive ixabepilone IV over 1 hour on days 1-5. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

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




• Phase II: Once the MTD is determined, additional patients receive ixabepilone as above at the MTD.

Patients are followed every 2 months.

Peerebom D, Batchelor T, Lesser G, et al.: NABTT 2111: a phase I trial of BMS-247550 for patients with recurrent high-grade gliomas. [Abstract] J Clin Oncol 23 (Suppl 16): A-1563, 129s, 2005.

Trial Contact Information

Trial Lead Organizations

New Approaches to Brain Tumor Therapy

David Peereboom, MD, Protocol chair		Ph: 216-445-6068; 800-862-7798 Email: peerebd@ccf.org

Registry Information
Official Title		A Phase I/II Trial of BMS-247550 for Treatment of Patients with Recurrent High-Grade Gliomas
Trial Start Date		2002-10-16
Trial Completion Date		2008-11-01
Registered in ClinicalTrials.gov		NCT00045708
Date Submitted to PDQ		2002-07-19
Information Last Verified		2005-12-21
NCI Grant/Contract Number		CA062475

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