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A Phase I/II Trial of BMS-247550 for Treatment of Patients With Recurrent High-Grade Gliomas

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00045708
First received: September 6, 2002
Last updated: April 8, 2013
Last verified: April 2013
  Purpose

Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. This phase I/II trial is studying the side effects and best dose of ixabepilone and how well it works in treating patients with recurrent glioma.


Condition Intervention Phase
Adult Anaplastic Astrocytoma
Adult Giant Cell Glioblastoma
Adult Gliosarcoma
Recurrent Adult Brain Tumor
Drug: ixabepilone
Other: pharmacological study
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Trial of BMS-247550 for Treatment of Patients With Recurrent High-grade Gliomas

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • MTD of BMS-247550 in patients with recurrent or progressive malignant glioma (Phase I) [ Time Frame: 5 days ] [ Designated as safety issue: Yes ]
  • Response rate of adult patients with recurrent glioma to BMS-247550 when administered at the MTD established in the phase I study (Phase II) [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
  • Pharmacokinetic parameters estimated using standard compartmental modeling and estimation of half-lives, transfer coefficients, and AUC [ Time Frame: Course 1, Day 1 and on Days 2, 3, 4, and 5 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The duration of progression free survival [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
  • Progression free-survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Will be estimated with 95% confidence intervals.

  • Overall survival [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
    Will be estimated with 95% confidence intervals.

  • Frequency of toxicity associated with BMS-247550 treatment [ Time Frame: Up to 7 days post treatment ] [ Designated as safety issue: Yes ]
    The proportion of patients with serious or life threatening toxicities will be estimated along with 95% confidence intervals.


Enrollment: 33
Study Start Date: October 2002
Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (ixabepilone)

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.

Drug: ixabepilone
Given IV
Other Names:
  • BMS-247550
  • epothilone B lactam
  • Ixempra
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose of BMS-247550 when administered to adults with recurrent malignant gliomas, receiving (Group A) or not receiving (Group B) anticonvulsants known to be metabolized by the P450 hepatic enzyme complex.

II. To describe the pharmacokinetics of this route of administration, measuring BMS-247550, and determine the effects of hepatic enzyme inducing drugs, such as anticonvulsants, on the pharmacokinetics.

III. To determine the response rate of adult patients with recurrent glioma to BMS-247550 administered at the MTD.

IV. To describe the toxicity associated with this regimen in adult patients with recurrent malignant gliomas.

SECONDARY OBJECTIVES:

I. To determine the percent of patients with 6 month progression free survival, duration of progression free survival and survival associated with this therapy in adult patients with recurrent malignant gliomas.

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.

PROJECTED ACCRUAL: 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have histologically proven malignant glioma (anaplastic astrocytoma or glioblastoma multiforme) which is progressive or recurrent following radiation therapy +/- chemotherapy; patients with previous low grade glioma who progressed after radiotherapy +/- chemotherapy and are biopsied and found to have a high grade glioma are eligible
  • Patients must have measurable progressive or recurrent malignant glioma by MRI or CT imaging
  • Patients must have recovered from severe toxicity of prior therapy; an interval of at least 3 months must have elapsed since the completion of the most recent course of radiation therapy while at least 3 weeks must have elapsed since the completion of a non-nitrosourea containing chemotherapy regimen and at least 6 weeks since the completion of a nitrosourea containing chemotherapy regimen
  • Patients must have a Karnofsky performance status >= 60% (i.e. the patient must be able to care for himself/herself with occasional help from others)
  • Absolute neutrophil count >= 1500/mm^3
  • Platelets >= 100,000/mm^3
  • HgB > 9 g/dl
  • Creatinine =< 1.5mg/dl
  • Total Bilirubin =< 1.5mg/dl
  • Transaminases =< 2.5 times above the upper limits of the institutional norm)
  • Patients must be able to provide written informed consent
  • Patients must have =< 2 prior chemotherapy regimens
  • Patients with the potential for pregnancy or impregnating their partner must agree to follow acceptable birth control methods to avoid conception; the anti-proliferative activity of this experimental drug may be harmful to the developing fetus or nursing infant; female patients of child-bearing potential must have a negative pregnancy test
  • Patients must have no concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix and breast; patients with prior malignancies must be disease-free for >= five years
  • Patients must be maintained on a stable corticosteroid regimen from the time of their baseline scan until the start of treatment
  • Patients must have a Mini Mental State Exam score of >= 15

Exclusion Criteria:

  • Patients with serious concurrent infection or medical illness, which would jeopardize the ability of the patient to receive the treatment outlined in this protocol with reasonable safety
  • Patients who are pregnant or breast-feeding
  • Patients with more than 2 prior chemotherapy regimens
  • Patients receiving concurrent investigational agents
  • Patients receiving any of the following medications which are known to be moderate to significant inhibitors of CYP3A4 are not eligible:

    • Antibiotics: clarithromycin, erythromycin, troleandomycin
    • Anti-HIV agents: delaviridine, nelfinavir, amprenavir, ritonavir, indinavir, saquinavir, lopinavir
    • Antifungals: itraconazole, ketoconazole, fluconazole (doses > 200mg/day), voriconazole
    • Antidepressants: nefazodone, fluovoxamine
    • Calcium channel blockers: verapamil, diltiazem
    • Miscellaneous: amiodarone NOTE: The above list of agents was provided by the National Cancer Institute as moderate to significant inhibitors of CYP3A4 that should not be administered with BMS; there may be other agents that have similar activities on CYP3A4, however these are currently unspecified; if investigators are concerned about a particular medication's inhibitory effect on CYP3A4, they are encouraged to consult local pharmacy services for more information and to contact the principal investigator to discuss the situation further
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00045708

Locations
United States, Maryland
New Approaches to Brain Tumor Therapy Consortium
Baltimore, Maryland, United States, 21231-1000
Sponsors and Collaborators
Investigators
Principal Investigator: David Peereboom New Approaches to Brain Tumor Therapy Consortium
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00045708     History of Changes
Other Study ID Numbers: NCI-2012-03016, NABTT 2111, CDR257118, U01CA062475
Study First Received: September 6, 2002
Last Updated: April 8, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Astrocytoma
Glioblastoma
Gliosarcoma
Glioma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors

ClinicalTrials.gov processed this record on November 25, 2014