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| ID | Type | Description | Link |
|---|---|---|---|
| NABTT 2111 | |||
| CDR257118 | |||
| U01CA062475 | U.S. NIH Grant/Contract | View source |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group A [Anticonvulsants] | Experimental | 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 Phase 1 |
|
| Group B [No Anticonvulsants] | Experimental | 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 Phase 1 |
|
| Group C [MTD-Phase 2) | Experimental | Maximum tolerated Dose (MTD-Phase 2) - subjects treated at dose determined by Group B Drug: ixabepilone Other Names: BMS-247550 epothilone B lactam Ixempra Given IV |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ixabepilone | Drug | Given IV |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Dose Limiting Toxicity to Determine Maximum Tolerated Dose (MTD) of BMS-247550 in Patients With Recurrent or Progressive Malignant Glioma | 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. | 21 days (1 cycle) |
| Group A (P450) Estimated MTD and Group B (nonP450) Estimated MTD of BMS-247550 in Patients With Recurrent or Progressive Malignant Glioma | 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. | 21 days (1 cycle) |
| Measure Pharmacokinetic Parameters Using Estimation of Half-lives Related to BMS-247550 and Anticonvulsants | T1/2,z = terminal half-life (T1/2) --- for a 2 or 3 compartment drug, idea of how long drugs stick around | 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 |
| Measure Pharmacokinetic Parameters Using Clearance as Related to BMS-247550 and Anticonvulsant Measurements | CL = clearance (how much volume of blood is cleared of the drug per unIT of time | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Duration of Overall Survival | 1.5 years | |
| The Duration of Progression Free Survival (Phase 2) | only patients treated on the nonP450 MTD | 1.5 years |
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Inclusion Criteria:
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:
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| Name | Affiliation | Role |
|---|---|---|
| David Peereboom, MD | National Cancer Institute (NCI) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Emory University | Atlanta | Georgia | 30322 | United States | ||
| Johns Hopkins University |
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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.
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
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Phase 1 |
|
Not provided
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| pharmacological study | Other | Correlative studies |
|
|
| Anticonvulsant | Drug | Drugs that induce hepatic Metabolic enzymes |
|
|
| Measure Pharmacokinetic Parameters Using Volume of Distribution at Steady State as Related to BMS-247550 and Anticonvulsants | Vss = volume of distribution at steady-state (how widely distributed in the body the drug gets) | 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 |
| Response Rate of Patients at the MTD | 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. | 3 years |
| Grade 3 and 4 Toxicity (NCI Common Terminology Criteria for Adverse Events Associated With BMS-247550 Treatment in at Least 5% of Patients | Proportion of patients with serious or life threatening toxicities in at least 5% of patients | Up to 30 days post treatment |
| Percent of Subjects With 6M Progression Free Survival at the Phase 2 Arm of Study | subjects who are progression free at 6 month scan | 6 months |
| Baltimore |
| Maryland |
| 21287 |
| United States |
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States |
| Wake Forest University | Winston-Salem | North Carolina | 27157 | United States |
| Cleveland Clinic | Cleveland | Ohio | 44106 | United States |
| FG001 | 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 |
| FG002 | Group 3 - MTD Phase 2 | Phase II: Once the MTD is determined, additional patients receive ixabepilone as above at the MTD. |
| COMPLETED |
|
| NOT COMPLETED |
|
|
| Phase 2 |
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Group A [Anticonvulsants] - Phase 1 | 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 |
| BG001 | Group B [No Anticonvulsants] - Phase 1 | 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 |
| BG002 | Phase 2 | Phase II: Once the MTD is determined, additional patients receive ixabepilone at the MTD. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Karnofsky Performance Status (KPS) | Performance status is a range where the higher score is the better score: 100 - Normal; no complaints; no evidence of disease; 90 - Able to carry on normal activity; minor signs or symptoms of disease, 80 - Normal activity with effort; some signs or symptoms of disease; 70 - Cares for self; unable to carry on normal activity or to do active work; 60 - Requires occasional assistance, but is able to care for most of his personal needs | Number | participants |
| |||||||||||||||
| Histology | pathology at time of study entry | Number | participants |
| |||||||||||||||
| Anticonvulsant Use | subjects were either on an anticonvulsant (EIAED) enzyme inducing antiepileptic drug or on an anticonvulsant that was not enzyme inducing (-EIAED) or on NO anticonvulsant | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Dose Limiting Toxicity to Determine Maximum Tolerated Dose (MTD) of BMS-247550 in Patients With Recurrent or Progressive Malignant Glioma | 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. | 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 | Posted | Number | DLTs | 21 days (1 cycle) |
|
|
| |||||||||||||||||||||||||||||||||
| Primary | Group A (P450) Estimated MTD and Group B (nonP450) Estimated MTD of BMS-247550 in Patients With Recurrent or Progressive Malignant Glioma | 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. | Posted | Number | mg/m2/day | 21 days (1 cycle) |
| ||||||||||||||||||||||||||||||||||||
| Primary | Measure Pharmacokinetic Parameters Using Estimation of Half-lives Related to BMS-247550 and Anticonvulsants | T1/2,z = terminal half-life (T1/2) --- for a 2 or 3 compartment drug, idea of how long drugs stick around | 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 | Posted | Mean | Standard Deviation | h | 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 |
| ||||||||||||||||||||||||||||||||||
| Primary | Measure Pharmacokinetic Parameters Using Clearance as Related to BMS-247550 and Anticonvulsant Measurements | CL = clearance (how much volume of blood is cleared of the drug per unIT of time | 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 | Posted | Mean | Standard Deviation | l/h/m2 | 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 |
| ||||||||||||||||||||||||||||||||||
| Primary | Measure Pharmacokinetic Parameters Using Volume of Distribution at Steady State as Related to BMS-247550 and Anticonvulsants | Vss = volume of distribution at steady-state (how widely distributed in the body the drug gets) | 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 | Posted | Mean | Standard Deviation | l/m2 | 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 |
| ||||||||||||||||||||||||||||||||||
| Primary | Response Rate of Patients at the MTD | 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. | 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. | Posted | Number | participants | 3 years |
|
| ||||||||||||||||||||||||||||||||||
| Primary | Grade 3 and 4 Toxicity (NCI Common Terminology Criteria for Adverse Events Associated With BMS-247550 Treatment in at Least 5% of Patients | Proportion of patients with serious or life threatening toxicities in at least 5% of patients | Posted | Count of Participants | Participants | Up to 30 days post treatment |
| ||||||||||||||||||||||||||||||||||||
| Secondary | Duration of Overall Survival | Posted | Median | 95% Confidence Interval | months | 1.5 years |
| ||||||||||||||||||||||||||||||||||||
| Secondary | The Duration of Progression Free Survival (Phase 2) | only patients treated on the nonP450 MTD | 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. | Posted | Median | 95% Confidence Interval | months | 1.5 years |
|
| |||||||||||||||||||||||||||||||||
| Secondary | Percent of Subjects With 6M Progression Free Survival at the Phase 2 Arm of Study | subjects who are progression free at 6 month scan | 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. | Posted | Number | 95% Confidence Interval | percent of patients | 6 months |
|
|
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).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Group A [Anticonvulsants] - Phase 1 | 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 | 0 | 21 | 1 | 21 | 21 | 21 |
| EG001 | Group B [No Anticonvulsants] - Phase 1 | 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 | 0 | 17 | 4 | 17 | 17 | 17 |
| EG002 | Phase 2 | Phase II: Once the MTD is determined, additional patients receive ixabepilone at the MTD. | 0 | 19 | 1 | 19 | 19 | 19 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Arthralgia | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| Febrile Neutropenia | Blood and lymphatic system disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| Neutrophil count decrease | Investigations | CTCAE (4.0) | Non-systematic Assessment |
| |
| White blood cell decrease | Investigations | CTCAE (4.0) | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Alopecia | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| Anemia (HGB) | Blood and lymphatic system disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment | heartburn |
|
| Edema limbs | General disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| Gastrointestinal pain | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment | abdominal pain/cramping |
|
| Generalized Muscle weakness | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Non-systematic Assessment | (not due to neuropathy) |
|
| Headache | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| Hypocalcemia | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| Neuralgia | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment | neuropathic pain |
|
| Pulmonary - other | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Non-systematic Assessment | pneumonia |
|
| abdominal pain | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| anorexia | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| arthralgia | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| constipation | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| diarrhea | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| fatigue | General disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| hyponatremia | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| hypophosphatemia | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| mucositis oral | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| myalgia | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| nausea | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| neuropathy - sensory | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| neutrophil count decrease | Investigations | CTCAE (4.0) | Non-systematic Assessment |
| |
| platelet count decrease | Investigations | CTCAE (4.0) | Non-systematic Assessment |
| |
| platelet count decrease | Investigations | CTCAE (4.0) | Non-systematic Assessment |
| |
| seizure | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| vomiting | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| weight gain | Investigations | CTCAE (4.0) | Non-systematic Assessment |
| |
| white blood cell decrease | Investigations | CTCAE (4.0) | Non-systematic Assessment |
| |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| flushing | Vascular disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| Febrile Neutropenia | Blood and lymphatic system disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| rash | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| Hyperglycemia | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment |
| |
| Aspartate aminotransferase | Investigations | CTCAE (4.0) | Non-systematic Assessment |
| |
| Alanine aminotransferase | Investigations | CTCAE (4.0) | Non-systematic Assessment |
| |
| hypokalemia | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment |
|
Phase 2 was completed using only nonP450 MTD (6.8mg/m21) as the MTD for P450 was not determined until the Phase 2 accrual had completed.
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Director Adult Brain Tumor Consortium | Johns Hopkins - Adult Brain Tumor Consortium (ABTC) | 410-955-8837 | jfisher@jhmi.edu |
| ID | Term |
|---|---|
| D001254 | Astrocytoma |
| D005909 | Glioblastoma |
| D018316 | Gliosarcoma |
| D001932 | Brain Neoplasms |
| ID | Term |
|---|---|
| D005910 | Glioma |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
| D016543 | Central Nervous System Neoplasms |
| D009423 | Nervous System Neoplasms |
| D009371 | Neoplasms by Site |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C430592 | ixabepilone |
| D000927 | Anticonvulsants |
| D051544 | Cytochrome P-450 CYP3A |
| ID | Term |
|---|---|
| D002491 | Central Nervous System Agents |
| D045506 | Therapeutic Uses |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D000072469 | Cytochrome P450 Family 3 |
| D003577 | Cytochrome P-450 Enzyme System |
| D003580 | Cytochromes |
| D045762 | Enzymes and Coenzymes |
| D010089 | Oxidoreductases, N-Demethylating |
| D000587 | Oxidoreductases Acting on CH-NH Group Donors |
| D010088 | Oxidoreductases |
| D004798 | Enzymes |
| D006899 | Mixed Function Oxygenases |
| D010105 | Oxygenases |
| D006420 | Hemeproteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
Not provided
Not provided
| Male |
|
| 70% |
|
| 80% |
|
| 90% |
|
| 100% |
|
| Malignant glioma |
|
| Anaplastic astrocytoma |
|
| -EIAED |
|
| None |
|
|
| Dose level 6.6mg/m2/day |
|
| Dose level 6.8mg/m2/day |
|
| Dose level 7.0mg/m2/day |
|
| Dose level 7.5mg/m2/day |
|
| Dose level 7.7mg/m2/day |
|
| Dose level 8.7mg/m2/day |
|
| Dose Level 9.5mg/m2/day |
|
| Dose level 9.6mg/m2/day |
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|
|
|
|
|
|
|
| OG002 | Phase 2 | Phase II: Once the MTD is determined, additional patients receive ixabepilone at the MTD. |
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