Phase 2
N=38
A Phase I/II Trial of BMS-247550 for Treatment of Patients With Recurrent High-Grade Gliomas
Adult Anaplastic Astrocytoma · Adult Giant Cell Glioblastoma · Adult Gliosarcoma · Recurrent Adult Brain Tumor
Bottom Line
View on ClinicalTrials.gov: NCT00045708 ↗Enrolled (actual)
38
Serious AEs
10.5%
Results posted
May 2017
Primary outcome: Primary: Number of Dose Limiting Toxicity to Determine Maximum Tolerated Dose (MTD) of BMS-247550 in Patients With Recurrent or Progressive Malignant Glioma — 0; 0; NA; 0 DLTs
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- ixabepilone (Drug); pharmacological study (Other); Anticonvulsant (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- National Cancer Institute (NCI)
- Primary completion
- May 2010
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Dose Limiting Toxicity to Determine Maximum Tolerated Dose (MTD) of BMS-247550 in Patients With Recurrent or Progressive Malignant Glioma |
0; 0; NA; 0; 0; NA | — |
| PRIMARY Group A (P450) Estimated MTD and Group B (nonP450) Estimated MTD of BMS-247550 in Patients With Recurrent or Progressive Malignant Glioma |
9.6; 6.8 | — |
| PRIMARY Measure Pharmacokinetic Parameters Using Estimation of Half-lives Related to BMS-247550 and Anticonvulsants |
13; 12 | — |
| PRIMARY Measure Pharmacokinetic Parameters Using Clearance as Related to BMS-247550 and Anticonvulsant Measurements |
36; 24 | — |
| PRIMARY Measure Pharmacokinetic Parameters Using Volume of Distribution at Steady State as Related to BMS-247550 and Anticonvulsants |
440; 290 | — |
| PRIMARY Response Rate of Patients at the MTD |
— | — |
| PRIMARY Grade 3 and 4 Toxicity (NCI Common Terminology Criteria for Adverse Events Associated With BMS-247550 Treatment in at Least 5% of Patients |
3; 4; 4; 1; 3; 4 | — |
| SECONDARY Duration of Overall Survival |
4.9; 7.1; 5.8 | — |
| SECONDARY The Duration of Progression Free Survival (Phase 2) |
1.5 | — |
| SECONDARY Percent of Subjects With 6M Progression Free Survival at the Phase 2 Arm of Study |
4 | — |
Summary
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.
Eligibility 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 = = 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: delavirdine, nelfinavir, amprenavir, ritonavir, indinavir, saquinavir, lopinavir
- Antifungals: itraconazole, ketoconazole, fluconazole (doses > 200mg/day), voriconazole
- Antidepressants: nefazodone, fluvoxamine
- 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
Data sourced from ClinicalTrials.gov (NCT00045708). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.