Adult Anaplastic AstrocytomaPhase 1/2NCT00045708

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

A Phase 1/2 study testing ixabepilone, pharmacological study and Anticonvulsant in people with Adult Anaplastic Astrocytoma and Adult Giant Cell Glioblastoma, run by National Cancer Institute (NCI) at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Adult Anaplastic Astrocytoma, Adult Giant Cell Glioblastoma, Adult Gliosarcoma
What is being tested?: ixabepilone, pharmacological study and Anticonvulsant
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 57 participants
Where: 5 sitesUnited States
Study dates: Oct 2002to May 2010
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Show all 16Show fewer

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

Who cannot join

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

Show all 11Show fewer

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

Trial locations and contacts

5 sites in 1 country.

City, postcode or hospital

5 sites in 1 country

United States5 sites

Emory University
Atlanta, Georgia, 30322
Johns Hopkins University
Baltimore, Maryland, 21287
Massachusetts General Hospital
Boston, Massachusetts, 02114
Cleveland Clinic
Cleveland, Ohio, 44106
Wake Forest University
Winston-Salem, North Carolina, 27157

Other trials in United States

About this study

Official title: A Phase I/II Trial of BMS-247550 for Treatment of Patients With Recurrent High-grade Gliomas

Read the detailed description

PRIMARY OBJECTIVES:

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:

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.

Conditions: Adult Anaplastic Astrocytoma, Adult Giant Cell Glioblastoma, Adult Gliosarcoma, Recurrent Adult Brain Tumor
Being tested: ixabepilone, pharmacological study, Anticonvulsant
Medical subject headings: Astrocytoma, Glioblastoma, Gliosarcoma, Brain Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ixabepiloneDrug
Also called BMS-247550, epothilone B lactam, Ixempra
Given IV
pharmacological studyOther
Also called pharmacological studies
Correlative studies
AnticonvulsantDrug
Also called P450
Drugs that induce hepatic Metabolic enzymes

Study groups in NCT00045708
Study group	Role	What they receive
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 Receives: Drug: ixabepilone; Other: pharmacological study; Drug: Anticonvulsant
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 Receives: Drug: ixabepilone; Other: pharmacological study
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 Receives: Drug: ixabepilone

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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 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)
Measured: 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.
Measured: 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
Measured: Up to 30 days post treatment

Secondary outcomes (3)

Duration of Overall Survival
Measured: 1.5 years
The Duration of Progression Free Survival (Phase 2)
only patients treated on the nonP450 MTD
Measured: 1.5 years
Percent of Subjects With 6M Progression Free Survival at the Phase 2 Arm of Study
subjects who are progression free at 6 month scan
Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 2002May 2010

First posted27 Jan 2003 (estimated)
Study startOct 2002
Primary completionMay 2010
Study completionMay 2010

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Adult Anaplastic AstrocytomaStudies of the same condition, open and under way.
More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 57 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00045708
Sponsor's protocol ID: NCI-2012-03016
Other IDs: NABTT 2111, CDR257118, U01CA062475
Status last verified: Sep 2017
First submitted: 6 Sep 2002
Last updated: 18 Oct 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Locally Advanced Solid Tumors, Metastatic Solid Tumors
RecruitingObservational study
Targeted Pediatric High-Grade Glioma Therapy
High Grade Glioma, Diffuse Intrinsic Pontine Glioma
RecruitingPhase 2
Study of Olutasidenib and Temozolomide in HGG
High Grade Glioma, Astrocytoma

All Adult Anaplastic Astrocytoma trials

Study at a glance

From the registry record, last updated by the sponsor on 18 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I/II Trial of BMS-247550 for Treatment of Patients With Recurrent High-grade Gliomas
ClinicalTrials.gov ID: NCT00045708
Acronym / sponsor ID: NCI-2012-03016
Conditions: Adult Anaplastic Astrocytoma, Adult Giant Cell Glioblastoma, Adult Gliosarcoma, Recurrent Adult Brain Tumor
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 57 participants (actual)
Lead sponsor: National Cancer Institute (NCI)US National Institutes of Health
Study start: Oct 2002
Primary completion: May 2010 (actual)
Study completion: May 2010 (actual)
First posted: 27 Jan 2003 (estimated)
Results: Posted 9 May 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

PRIMARY OBJECTIVES:

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.

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:

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.

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.

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

Patients are followed every 2 months.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Group A [Anticonvulsants]	Experimental	Drug: ixabepilone, Other: pharmacological study, Drug: AnticonvulsantPhase 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	Drug: ixabepilone, Other: pharmacological studyPhase 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	Drug: ixabepiloneMaximum 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

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (16 listed)

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

Key exclusion criteria (11 listed)

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:

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
ixabepiloneAlso: BMS-247550, epothilone B lactam, IxempraGiven IV	Drug	Group A [Anticonvulsants], Group B [No Anticonvulsants], Group C [MTD-Phase 2)
pharmacological studyAlso: pharmacological studiesCorrelative studies	Other	Group A [Anticonvulsants], Group B [No Anticonvulsants]
AnticonvulsantAlso: P450Drugs that induce hepatic Metabolic enzymes	Drug	Group A [Anticonvulsants]

Primary outcome

Number of Dose Limiting Toxicity to Determine Maximum Tolerated Dose (MTD) of BMS-247550 in Patients With Recurrent or Progressive Malignant Glioma
Time frame: 21 days (1 cycle)
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.
Group A (P450) Estimated MTD and Group B (nonP450) Estimated MTD of BMS-247550 in Patients With Recurrent or Progressive Malignant Glioma
Time frame: 21 days (1 cycle)
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.
Measure Pharmacokinetic Parameters Using Estimation of Half-lives Related to BMS-247550 and Anticonvulsants
Time frame: 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
T1/2,z = terminal half-life (T1/2) --- for a 2 or 3 compartment drug, idea of how long drugs stick around
Measure Pharmacokinetic Parameters Using Clearance as Related to BMS-247550 and Anticonvulsant Measurements
Time frame: 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
CL = clearance (how much volume of blood is cleared of the drug per unIT of time
Measure Pharmacokinetic Parameters Using Volume of Distribution at Steady State as Related to BMS-247550 and Anticonvulsants
Time frame: 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
Vss = volume of distribution at steady-state (how widely distributed in the body the drug gets)
Response Rate of Patients at the MTD
Time frame: 3 years
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.
Grade 3 and 4 Toxicity (NCI Common Terminology Criteria for Adverse Events Associated With BMS-247550 Treatment in at Least 5% of Patients
Time frame: Up to 30 days post treatment
Proportion of patients with serious or life threatening toxicities in at least 5% of patients

3 secondary outcomes

Duration of Overall Survival
Time frame: 1.5 years
The Duration of Progression Free Survival (Phase 2)
Time frame: 1.5 years
Percent of Subjects With 6M Progression Free Survival at the Phase 2 Arm of Study
Time frame: 6 months

Results and safety

Results posted to the registry on 9 May 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Group A [Anticonvulsants]	21	21
Group B [No Anticonvulsants]	17	16
Group 3 - MTD Phase 2	0	0

Primary outcome: Number of Dose Limiting Toxicity to Determine Maximum Tolerated Dose (MTD) of BMS-247550 in Patients With Recurrent or Progressive Malignant Glioma

Time frame: 21 days (1 cycle). Number. Unit: DLTs

Measure	Group A [Anticonvulsants] n = 21	Group B [No Anticonvulsants] n = 17	Group 3 - MTD (6.8mg/m2/Day) Phase 2 n = 19
Dose level 5.0mg/m2/day	0	0	NA
Dose level 6.0mg/m2/day	0	0	NA
Dose level 6.6mg/m2/day	NA	0	NA
Dose level 6.8mg/m2/day	NA	1	0
Dose level 7.0mg/m2/day	0	2	NA
Dose level 7.5mg/m2/day	NA	1	NA
Dose level 7.7mg/m2/day	0	NA	NA
Dose level 8.7mg/m2/day	0	NA	NA

Population analysed: 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

Primary outcome: Group A (P450) Estimated MTD and Group B (nonP450) Estimated MTD of BMS-247550 in Patients With Recurrent or Progressive Malignant Glioma

Time frame: 21 days (1 cycle). Number. Unit: mg/m2/day

Measure	Group A [Anticonvulsants] n = 21	Group B [No Anticonvulsants] n = 17
Value	9.6	6.8

Primary outcome: Measure Pharmacokinetic Parameters Using Estimation of Half-lives Related to BMS-247550 and Anticonvulsants

Time frame: 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. Mean (Standard Deviation). Unit: h

Measure	Group A [Anticonvulsants] n = 13	Group B [No Anticonvulsants] n = 16
Value	13 (11)	12 (3.7)

Population analysed: 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

Primary outcome: Measure Pharmacokinetic Parameters Using Clearance as Related to BMS-247550 and Anticonvulsant Measurements

Time frame: 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. Mean (Standard Deviation). Unit: l/h/m2

Measure	Group A [Anticonvulsants] n = 13	Group B [No Anticonvulsants] n = 16
Value	36 (11)	24 (9.2)

Population analysed: 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

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: 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 reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Group A [Anticonvulsants] - Phase 1	1 of 21 (4.8%)	21 of 21 (100%)	0 of 21
Group B [No Anticonvulsants] - Phase 1	4 of 17 (23.5%)	17 of 17 (100%)	0 of 17
Phase 2	1 of 19 (5.3%)	19 of 19 (100%)	0 of 19

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Oct 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

David Peereboom, MD principal investigator

National Cancer Institute (NCI)

5 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Dose Limiting Toxicity to Determine Maximum Tolerated Dose (MTD) of BMS-247550 in Patients With Recurrent or Progressive Malignant Glioma (time frame: 21 days (1 cycle)). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00045708.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Oct 2017.