Trial Outcomes & Findings for A Phase I/II Trial of BMS-247550 for Treatment of Patients With Recurrent High-Grade Gliomas (NCT NCT00045708)

Last Updated: 2017-10-18

Results Overview

Starting dose for both Group A and Group B was 5mg/m2/day. A continuing reassessment method (CRM) was employed independently for each group to estimate the maximum tolerated dose. Only toxicity observed during 1st cycle of treatment (21 days) was used for dose finding. Dose limiting toxicity (DLT) defined as: ANC\<500/ul, platelets\<25,000, febrile neutropenia or treatment-related grade 3 or 4 non-hematologic toxicity with the exception of nausea and vomiting.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

57 participants

Primary outcome timeframe

21 days (1 cycle)

Results posted on

2017-10-18

Participant Flow

Fifty-seven subjects were enrolled in the Phase 1 and Phase 2 between October 2002 and November 2005. Subjects were enrolled from outpatient medical clinics

Please note that 4 subjects in Arm B (non-P450- 6.8mg/m2) were used in the analysis and total n for the Phase 2. Hence, 19 new subjects were accrued to the Phase 2 portion of the study at the 6.8mg/m2 dose level, but the 4 subjects already treated at 6.8gmg/m2 were included in Phase 2 analysis.

Participant milestones

Participant milestones
Measure	Group A [Anticonvulsants] Phase I: Dose Escalation - 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. Pharmacological Study ixabepilone: Given IV pharmacological study: Correlative studies	Group B [No Anticonvulsants] Phase I: Dose Escalation - 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. Pharmacological Study ixabepilone: Given IV pharmacological study: Correlative studies	Group 3 - MTD Phase 2 Phase II: Once the MTD is determined, additional patients receive ixabepilone as above at the MTD.
Phase 1 STARTED	21	17	0
Phase 1 COMPLETED	21	16	0
Phase 1 NOT COMPLETED	0	1	0
Phase 2 STARTED	0	0	19
Phase 2 COMPLETED	0	0	19
Phase 2 NOT COMPLETED	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Group A [Anticonvulsants] Phase I: Dose Escalation - 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. Pharmacological Study ixabepilone: Given IV pharmacological study: Correlative studies	Group B [No Anticonvulsants] Phase I: Dose Escalation - 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. Pharmacological Study ixabepilone: Given IV pharmacological study: Correlative studies	Group 3 - MTD Phase 2 Phase II: Once the MTD is determined, additional patients receive ixabepilone as above at the MTD.
Phase 1 early progressive disease	0	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group A [Anticonvulsants] - Phase 1 n=21 Participants Phase I: Dose Escalation - 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. Pharmacological Study ixabepilone: Given IV pharmacological study: Correlative studies	Group B [No Anticonvulsants] - Phase 1 n=17 Participants Phase I: Dose Escalation - 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. Pharmacological Study ixabepilone: Given IV pharmacological study: Correlative studies	Phase 2 n=19 Participants Phase II: Once the MTD is determined, additional patients receive ixabepilone at the MTD.	Total n=57 Participants Total of all reporting groups
Age, Continuous	53 years n=5 Participants	56 years n=7 Participants	53 years n=5 Participants	54 years n=4 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	12 Participants n=7 Participants	9 Participants n=5 Participants	26 Participants n=4 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants	31 Participants n=4 Participants
Karnofsky Performance Status (KPS) 60%	2 participants n=5 Participants	3 participants n=7 Participants	0 participants n=5 Participants	5 participants n=4 Participants
Karnofsky Performance Status (KPS) 70%	2 participants n=5 Participants	3 participants n=7 Participants	2 participants n=5 Participants	9 participants n=4 Participants
Karnofsky Performance Status (KPS) 80%	6 participants n=5 Participants	3 participants n=7 Participants	5 participants n=5 Participants	14 participants n=4 Participants
Karnofsky Performance Status (KPS) 90%	10 participants n=5 Participants	8 participants n=7 Participants	6 participants n=5 Participants	26 participants n=4 Participants
Karnofsky Performance Status (KPS) 100%	1 participants n=5 Participants	0 participants n=7 Participants	6 participants n=5 Participants	7 participants n=4 Participants
Histology Glioblastoma multiforme	15 participants n=5 Participants	14 participants n=7 Participants	14 participants n=5 Participants	46 participants n=4 Participants
Histology Malignant glioma	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	2 participants n=4 Participants
Histology Anaplastic astrocytoma	5 participants n=5 Participants	3 participants n=7 Participants	4 participants n=5 Participants	13 participants n=4 Participants
Anticonvulsant Use +EIAED	21 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	21 participants n=4 Participants
Anticonvulsant Use -EIAED	0 participants n=5 Participants	12 participants n=7 Participants	10 participants n=5 Participants	25 participants n=4 Participants
Anticonvulsant Use None	0 participants n=5 Participants	5 participants n=7 Participants	9 participants n=5 Participants	15 participants n=4 Participants

PRIMARY outcome

Timeframe: 21 days (1 cycle)

Population: 4 subjects from Group B (Phase 1) were included in Group 3 (Phase 2). Only those on non-anticonvulsants at the dose of 6.8mg/m2/day were treated in Phase 2. No subjects treated at the MTD for P450, as the accrual goal for phase 2 reached before MTD for p450 was determined. P450 MTD determined as 9.6mg/m2 per CRM after all enrollment of phase 2

Outcome measures

Outcome measures
Measure	Group A [Anticonvulsants] n=21 Participants Phase I: Dose Escalation - 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. Pharmacological Study ixabepilone: Given IV pharmacological study: Correlative studies	Group B [No Anticonvulsants] n=17 Participants Phase I: Dose Escalation - 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. Pharmacological Study ixabepilone: Given IV pharmacological study: Correlative studies	Group 3 - MTD (6.8mg/m2/Day) Phase 2 n=19 Participants Phase II: Once the MTD is determined, additional patients receive ixabepilone as above at the MTD. ixabepilone: Given IV MTD for no anticonvulsant arm = 6.8mg/m2/day MTD for anticonvulsant arm = 9.6mg/m2/day Only no anticonvulsant subjects at 6.8mg/m2/day treated in Phase 2
Number of Dose Limiting Toxicity to Determine Maximum Tolerated Dose (MTD) of BMS-247550 in Patients With Recurrent or Progressive Malignant Glioma Dose level 7.0mg/m2/day	0 DLTs	2 DLTs	NA DLTs In phase 2 all subjects were treated at MTD from phase 1 group b - 6.8mg/m2/day
Number of Dose Limiting Toxicity to Determine Maximum Tolerated Dose (MTD) of BMS-247550 in Patients With Recurrent or Progressive Malignant Glioma Dose level 5.0mg/m2/day	0 DLTs	0 DLTs	NA DLTs In phase 2 all subjects were treated at MTD from phase 1 group b - 6.8mg/m2/day
Number of Dose Limiting Toxicity to Determine Maximum Tolerated Dose (MTD) of BMS-247550 in Patients With Recurrent or Progressive Malignant Glioma Dose level 6.0mg/m2/day	0 DLTs	0 DLTs	NA DLTs In phase 2 all subjects were treated at MTD from phase 1 group b - 6.8mg/m2/day
Number of Dose Limiting Toxicity to Determine Maximum Tolerated Dose (MTD) of BMS-247550 in Patients With Recurrent or Progressive Malignant Glioma Dose level 6.6mg/m2/day	NA DLTs this cohort was not tested in the anticonvulsant arm of study	0 DLTs	NA DLTs In phase 2 all subjects were treated at MTD from phase 1 group b - 6.8mg/m2/day
Number of Dose Limiting Toxicity to Determine Maximum Tolerated Dose (MTD) of BMS-247550 in Patients With Recurrent or Progressive Malignant Glioma Dose level 6.8mg/m2/day	NA DLTs this cohort was not tested in the anticonvulsant arm of study	1 DLTs	0 DLTs
Number of Dose Limiting Toxicity to Determine Maximum Tolerated Dose (MTD) of BMS-247550 in Patients With Recurrent or Progressive Malignant Glioma Dose level 7.5mg/m2/day	NA DLTs this cohort was not tested in the anticonvulsant arm of study	1 DLTs	NA DLTs In phase 2 all subjects were treated at MTD from phase 1 group b - 6.8mg/m2/day
Number of Dose Limiting Toxicity to Determine Maximum Tolerated Dose (MTD) of BMS-247550 in Patients With Recurrent or Progressive Malignant Glioma Dose level 7.7mg/m2/day	0 DLTs	NA DLTs this cohort was not tested in the no anticonvulsant arm of study	NA DLTs In phase 2 all subjects were treated at MTD from phase 1 group b - 6.8mg/m2/day
Number of Dose Limiting Toxicity to Determine Maximum Tolerated Dose (MTD) of BMS-247550 in Patients With Recurrent or Progressive Malignant Glioma Dose level 8.7mg/m2/day	0 DLTs	NA DLTs this cohort was not tested in the no anticonvulsant arm of study	NA DLTs In phase 2 all subjects were treated at MTD from phase 1 group b - 6.8mg/m2/day
Number of Dose Limiting Toxicity to Determine Maximum Tolerated Dose (MTD) of BMS-247550 in Patients With Recurrent or Progressive Malignant Glioma Dose Level 9.5mg/m2/day	0 DLTs	NA DLTs this cohort was not tested in the no anticonvulsant arm of study	NA DLTs In phase 2 all subjects were treated at MTD from phase 1 group b - 6.8mg/m2/day
Number of Dose Limiting Toxicity to Determine Maximum Tolerated Dose (MTD) of BMS-247550 in Patients With Recurrent or Progressive Malignant Glioma Dose level 9.6mg/m2/day	1 DLTs	NA DLTs this cohort was not tested in the no anticonvulsant arm of study	NA DLTs In phase 2 all subjects were treated at MTD from phase 1 group b - 6.8mg/m2/day

PRIMARY outcome

Timeframe: 21 days (1 cycle)

Outcome measures

Outcome measures
Measure	Group A [Anticonvulsants] n=21 Participants Phase I: Dose Escalation - 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. Pharmacological Study ixabepilone: Given IV pharmacological study: Correlative studies	Group B [No Anticonvulsants] n=17 Participants Phase I: Dose Escalation - 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. Pharmacological Study ixabepilone: Given IV pharmacological study: Correlative studies	Group 3 - MTD (6.8mg/m2/Day) Phase 2 Phase II: Once the MTD is determined, additional patients receive ixabepilone as above at the MTD. ixabepilone: Given IV MTD for no anticonvulsant arm = 6.8mg/m2/day MTD for anticonvulsant arm = 9.6mg/m2/day Only no anticonvulsant subjects at 6.8mg/m2/day treated in Phase 2
Group A (P450) Estimated MTD and Group B (nonP450) Estimated MTD of BMS-247550 in Patients With Recurrent or Progressive Malignant Glioma	9.6 mg/m2/day	6.8 mg/m2/day	—

PRIMARY outcome

Timeframe: Course 1, Day 1 (pre-infusion, midpoint of infusion, 5min prior to end of infusion, 15min, 30min, 1hr, 2hr, 3hr, 4hr and 6hr post infusion

Population: 13 of the 21 samples for P450 collected day 1 sample set and 16 of the 17 samples for the nonP40 collected day 1 sample set

T1/2,z = terminal half-life (T1/2) --- for a 2 or 3 compartment drug, idea of how long drugs stick around

Outcome measures

Outcome measures
Measure	Group A [Anticonvulsants] n=13 Participants Phase I: Dose Escalation - 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. Pharmacological Study ixabepilone: Given IV pharmacological study: Correlative studies	Group B [No Anticonvulsants] n=16 Participants Phase I: Dose Escalation - 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. Pharmacological Study ixabepilone: Given IV pharmacological study: Correlative studies	Group 3 - MTD (6.8mg/m2/Day) Phase 2 Phase II: Once the MTD is determined, additional patients receive ixabepilone as above at the MTD. ixabepilone: Given IV MTD for no anticonvulsant arm = 6.8mg/m2/day MTD for anticonvulsant arm = 9.6mg/m2/day Only no anticonvulsant subjects at 6.8mg/m2/day treated in Phase 2
Measure Pharmacokinetic Parameters Using Estimation of Half-lives Related to BMS-247550 and Anticonvulsants	13 h Standard Deviation 11	12 h Standard Deviation 3.7	—

PRIMARY outcome

Timeframe: Course 1, Day 1 (pre-infusion, midpoint of infusion, 5min prior to end of infusion, 15min, 30min, 1hr, 2hr, 3hr, 4hr and 6hr post infusion

Population: 13 of the 21 samples for P450 collected day 1 sample set and 16 of the 17 samples for the nonP40 collected day 1 sample set

CL = clearance (how much volume of blood is cleared of the drug per unIT of time

Outcome measures

Outcome measures
Measure	Group A [Anticonvulsants] n=13 Participants Phase I: Dose Escalation - 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. Pharmacological Study ixabepilone: Given IV pharmacological study: Correlative studies	Group B [No Anticonvulsants] n=16 Participants Phase I: Dose Escalation - 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. Pharmacological Study ixabepilone: Given IV pharmacological study: Correlative studies	Group 3 - MTD (6.8mg/m2/Day) Phase 2 Phase II: Once the MTD is determined, additional patients receive ixabepilone as above at the MTD. ixabepilone: Given IV MTD for no anticonvulsant arm = 6.8mg/m2/day MTD for anticonvulsant arm = 9.6mg/m2/day Only no anticonvulsant subjects at 6.8mg/m2/day treated in Phase 2
Measure Pharmacokinetic Parameters Using Clearance as Related to BMS-247550 and Anticonvulsant Measurements	36 l/h/m2 Standard Deviation 11	24 l/h/m2 Standard Deviation 9.2	—

PRIMARY outcome

Timeframe: Course 1, Day 1 (pre-infusion, midpoint of infusion, 5min prior to end of infusion, 15min, 30min, 1hr, 2hr, 3hr, 4hr and 6hr post infusion

Population: 13 of the 21 samples for P450 collected day 1 sample set and 16 of the 17 samples for the nonP40 collected day 1 sample set

Vss = volume of distribution at steady-state (how widely distributed in the body the drug gets)

Outcome measures

Outcome measures
Measure	Group A [Anticonvulsants] n=13 Participants Phase I: Dose Escalation - 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. Pharmacological Study ixabepilone: Given IV pharmacological study: Correlative studies	Group B [No Anticonvulsants] n=16 Participants Phase I: Dose Escalation - 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. Pharmacological Study ixabepilone: Given IV pharmacological study: Correlative studies	Group 3 - MTD (6.8mg/m2/Day) Phase 2 Phase II: Once the MTD is determined, additional patients receive ixabepilone as above at the MTD. ixabepilone: Given IV MTD for no anticonvulsant arm = 6.8mg/m2/day MTD for anticonvulsant arm = 9.6mg/m2/day Only no anticonvulsant subjects at 6.8mg/m2/day treated in Phase 2
Measure Pharmacokinetic Parameters Using Volume of Distribution at Steady State as Related to BMS-247550 and Anticonvulsants	440 l/m2 Standard Deviation 410	290 l/m2 Standard Deviation 160	—

PRIMARY outcome

Timeframe: 3 years

Population: no objective responses observed. 19 patients treated at the MTD from during Phase 2 and 4 patients treated at the MTD during the Phase 1 nonP450 arm 2 were included in the response analysis.

Complete Response: Complete disappearance of all tumor on MRI scan, off all glucocorticoids with stable/improving neurologic exam for min4 wks. Partial Response: Greater than or equal to 50% reduction in tumor size on volumetric MRI scan, on a stable/decreasing dose of glucocorticoids, with stable/improving neurologic examination for min 4 wks. Progressive Disease: Progressive neurologic abnormalities not explained by causes unrelated to tumor progression (e.g. anticonvulsant or corticosteroid toxicity, electrolyte abnormalities, hyperglycemia, etc.) or a greater than 25% increase in the volume of the tumor by MRI scan. If neurologic status deteriorates, on stable/increasing dose of steroids, or if new lesions appear on serial MRI, further study treatment will be discontinued. Stable Disease: A patient whose clinical status and MRI volumetrics do not meet the criteria for Complete Response, Partial Response or Progressive Disease.

Outcome measures

Outcome measures
Measure	Group A [Anticonvulsants] n=23 Participants Phase I: Dose Escalation - 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. Pharmacological Study ixabepilone: Given IV pharmacological study: Correlative studies	Group B [No Anticonvulsants] Phase I: Dose Escalation - 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. Pharmacological Study ixabepilone: Given IV pharmacological study: Correlative studies	Group 3 - MTD (6.8mg/m2/Day) Phase 2 Phase II: Once the MTD is determined, additional patients receive ixabepilone as above at the MTD. ixabepilone: Given IV MTD for no anticonvulsant arm = 6.8mg/m2/day MTD for anticonvulsant arm = 9.6mg/m2/day Only no anticonvulsant subjects at 6.8mg/m2/day treated in Phase 2
Response Rate of Patients at the MTD	0 participants	—	—

PRIMARY outcome

Timeframe: Up to 30 days post treatment

Proportion of patients with serious or life threatening toxicities in at least 5% of patients

Outcome measures

Outcome measures
Measure	Group A [Anticonvulsants] n=21 Participants Phase I: Dose Escalation - 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. Pharmacological Study ixabepilone: Given IV pharmacological study: Correlative studies	Group B [No Anticonvulsants] n=17 Participants Phase I: Dose Escalation - 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. Pharmacological Study ixabepilone: Given IV pharmacological study: Correlative studies	Group 3 - MTD (6.8mg/m2/Day) Phase 2 n=19 Participants Phase II: Once the MTD is determined, additional patients receive ixabepilone as above at the MTD. ixabepilone: Given IV MTD for no anticonvulsant arm = 6.8mg/m2/day MTD for anticonvulsant arm = 9.6mg/m2/day Only no anticonvulsant subjects at 6.8mg/m2/day treated in Phase 2
Grade 3 and 4 Toxicity (NCI Common Terminology Criteria for Adverse Events Associated With BMS-247550 Treatment in at Least 5% of Patients Transfusion:pRBCs	0 Participants	1 Participants	3 Participants
Grade 3 and 4 Toxicity (NCI Common Terminology Criteria for Adverse Events Associated With BMS-247550 Treatment in at Least 5% of Patients Anemia (HGB)	0 Participants	0 Participants	2 Participants
Grade 3 and 4 Toxicity (NCI Common Terminology Criteria for Adverse Events Associated With BMS-247550 Treatment in at Least 5% of Patients Hyponatremia	0 Participants	0 Participants	1 Participants
Grade 3 and 4 Toxicity (NCI Common Terminology Criteria for Adverse Events Associated With BMS-247550 Treatment in at Least 5% of Patients Neutropenia (ANC)	3 Participants	4 Participants	4 Participants
Grade 3 and 4 Toxicity (NCI Common Terminology Criteria for Adverse Events Associated With BMS-247550 Treatment in at Least 5% of Patients WBC (leukopenia)	1 Participants	3 Participants	4 Participants
Grade 3 and 4 Toxicity (NCI Common Terminology Criteria for Adverse Events Associated With BMS-247550 Treatment in at Least 5% of Patients Hypophosphatemia (PO4)	1 Participants	1 Participants	2 Participants

SECONDARY outcome

Timeframe: 1.5 years

Outcome measures

Outcome measures
Measure	Group A [Anticonvulsants] n=21 Participants Phase I: Dose Escalation - 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. Pharmacological Study ixabepilone: Given IV pharmacological study: Correlative studies	Group B [No Anticonvulsants] n=17 Participants Phase I: Dose Escalation - 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. Pharmacological Study ixabepilone: Given IV pharmacological study: Correlative studies	Group 3 - MTD (6.8mg/m2/Day) Phase 2 n=19 Participants Phase II: Once the MTD is determined, additional patients receive ixabepilone as above at the MTD. ixabepilone: Given IV MTD for no anticonvulsant arm = 6.8mg/m2/day MTD for anticonvulsant arm = 9.6mg/m2/day Only no anticonvulsant subjects at 6.8mg/m2/day treated in Phase 2
Duration of Overall Survival	4.9 months Interval 3.4 to 9.6	7.1 months Interval 2.9 to 15.4	5.8 months Interval 5.0 to 8.6

SECONDARY outcome

Timeframe: 1.5 years

Population: 19 patients treated at the MTD from during Phase 2 and 4 patients treated at the MTD during the Phase 1 nonP450 arm 2 were included in the response analysis.

only patients treated on the nonP450 MTD

Outcome measures

Outcome measures
Measure	Group A [Anticonvulsants] n=23 Participants Phase I: Dose Escalation - 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. Pharmacological Study ixabepilone: Given IV pharmacological study: Correlative studies	Group B [No Anticonvulsants] Phase I: Dose Escalation - 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. Pharmacological Study ixabepilone: Given IV pharmacological study: Correlative studies	Group 3 - MTD (6.8mg/m2/Day) Phase 2 Phase II: Once the MTD is determined, additional patients receive ixabepilone as above at the MTD. ixabepilone: Given IV MTD for no anticonvulsant arm = 6.8mg/m2/day MTD for anticonvulsant arm = 9.6mg/m2/day Only no anticonvulsant subjects at 6.8mg/m2/day treated in Phase 2
The Duration of Progression Free Survival (Phase 2)	1.5 months Interval 1.3 to 2.3	—	—

SECONDARY outcome

Timeframe: 6 months

Population: 19 patients treated at the MTD from during Phase 2 and 4 patients treated at the MTD during the Phase 1 nonP450 arm 2 were included in the response analysis.

subjects who are progression free at 6 month scan

Outcome measures

Outcome measures
Measure	Group A [Anticonvulsants] n=23 Participants Phase I: Dose Escalation - 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. Pharmacological Study ixabepilone: Given IV pharmacological study: Correlative studies	Group B [No Anticonvulsants] Phase I: Dose Escalation - 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. Pharmacological Study ixabepilone: Given IV pharmacological study: Correlative studies	Group 3 - MTD (6.8mg/m2/Day) Phase 2 Phase II: Once the MTD is determined, additional patients receive ixabepilone as above at the MTD. ixabepilone: Given IV MTD for no anticonvulsant arm = 6.8mg/m2/day MTD for anticonvulsant arm = 9.6mg/m2/day Only no anticonvulsant subjects at 6.8mg/m2/day treated in Phase 2
Percent of Subjects With 6M Progression Free Survival at the Phase 2 Arm of Study	4 percent of patients Interval 0.0 to 22.0	—	—

Adverse Events

Group A [Anticonvulsants] - Phase 1

Serious events: 1 serious events

Other events: 21 other events

Deaths: 0 deaths

Group B [No Anticonvulsants] - Phase 1

Serious events: 4 serious events

Other events: 17 other events

Deaths: 0 deaths

Phase 2

Serious events: 1 serious events

Other events: 19 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Group A [Anticonvulsants] - Phase 1 n=21 participants at risk Phase I: Dose Escalation - 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. Pharmacological Study ixabepilone: Given IV pharmacological study: Correlative studies	Group B [No Anticonvulsants] - Phase 1 n=17 participants at risk Phase I: Dose Escalation - 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. Pharmacological Study ixabepilone: Given IV pharmacological study: Correlative studies	Phase 2 n=19 participants at risk Phase II: Once the MTD is determined, additional patients receive ixabepilone at the MTD.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/21 • adverse events were collected while patients were on study and for 30 days post last day of treatment. For most patients this was 6 months. Subjects were evaluated for dose limiting toxicities (DLTs) for Phase 1 only during the first cycle (first 28 days - or until they started Cycle 2, if cycle 1 was delayed for any reason).	5.9% 1/17 • Number of events 1 • adverse events were collected while patients were on study and for 30 days post last day of treatment. For most patients this was 6 months. Subjects were evaluated for dose limiting toxicities (DLTs) for Phase 1 only during the first cycle (first 28 days - or until they started Cycle 2, if cycle 1 was delayed for any reason).	0.00% 0/19 • adverse events were collected while patients were on study and for 30 days post last day of treatment. For most patients this was 6 months. Subjects were evaluated for dose limiting toxicities (DLTs) for Phase 1 only during the first cycle (first 28 days - or until they started Cycle 2, if cycle 1 was delayed for any reason).
Blood and lymphatic system disorders Febrile Neutropenia	0.00% 0/21 • adverse events were collected while patients were on study and for 30 days post last day of treatment. For most patients this was 6 months. Subjects were evaluated for dose limiting toxicities (DLTs) for Phase 1 only during the first cycle (first 28 days - or until they started Cycle 2, if cycle 1 was delayed for any reason).	5.9% 1/17 • Number of events 1 • adverse events were collected while patients were on study and for 30 days post last day of treatment. For most patients this was 6 months. Subjects were evaluated for dose limiting toxicities (DLTs) for Phase 1 only during the first cycle (first 28 days - or until they started Cycle 2, if cycle 1 was delayed for any reason).	0.00% 0/19 • adverse events were collected while patients were on study and for 30 days post last day of treatment. For most patients this was 6 months. Subjects were evaluated for dose limiting toxicities (DLTs) for Phase 1 only during the first cycle (first 28 days - or until they started Cycle 2, if cycle 1 was delayed for any reason).
Investigations Neutrophil count decrease	4.8% 1/21 • Number of events 4 • adverse events were collected while patients were on study and for 30 days post last day of treatment. For most patients this was 6 months. Subjects were evaluated for dose limiting toxicities (DLTs) for Phase 1 only during the first cycle (first 28 days - or until they started Cycle 2, if cycle 1 was delayed for any reason).	5.9% 1/17 • Number of events 1 • adverse events were collected while patients were on study and for 30 days post last day of treatment. For most patients this was 6 months. Subjects were evaluated for dose limiting toxicities (DLTs) for Phase 1 only during the first cycle (first 28 days - or until they started Cycle 2, if cycle 1 was delayed for any reason).	5.3% 1/19 • Number of events 1 • adverse events were collected while patients were on study and for 30 days post last day of treatment. For most patients this was 6 months. Subjects were evaluated for dose limiting toxicities (DLTs) for Phase 1 only during the first cycle (first 28 days - or until they started Cycle 2, if cycle 1 was delayed for any reason).
Investigations White blood cell decrease	0.00% 0/21 • adverse events were collected while patients were on study and for 30 days post last day of treatment. For most patients this was 6 months. Subjects were evaluated for dose limiting toxicities (DLTs) for Phase 1 only during the first cycle (first 28 days - or until they started Cycle 2, if cycle 1 was delayed for any reason).	5.9% 1/17 • Number of events 1 • adverse events were collected while patients were on study and for 30 days post last day of treatment. For most patients this was 6 months. Subjects were evaluated for dose limiting toxicities (DLTs) for Phase 1 only during the first cycle (first 28 days - or until they started Cycle 2, if cycle 1 was delayed for any reason).	0.00% 0/19 • adverse events were collected while patients were on study and for 30 days post last day of treatment. For most patients this was 6 months. Subjects were evaluated for dose limiting toxicities (DLTs) for Phase 1 only during the first cycle (first 28 days - or until they started Cycle 2, if cycle 1 was delayed for any reason).

Other adverse events

Additional Information

Director Adult Brain Tumor Consortium

Johns Hopkins - Adult Brain Tumor Consortium (ABTC)

Phone: 410-955-8837

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60