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| ID | Type | Description | Link |
|---|---|---|---|
| PBTC-006 | Other Identifier | Pediatric Brain Tumor Consortium Protocol Identifier | |
| U01CA081457 | U.S. NIH Grant/Contract | View source | |
| CDR0000068761 | Registry Identifier | PDQ (Physician Data Query) |
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Poor accrual
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Phase I/II trial to estimate the maximum tolerated dose of imatinib mesylate in newly diagnosed brain stem gliomas and recurrent high grade gliomas and to assess the effectiveness of imatinib mesylate in treating young patients who have newly diagnosed intrinsic brain stem glioma. Imatinib mesylate may interfere with the growth of tumor cells by blocking the enzymes necessary for their growth. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining imatinib mesylate with radiation therapy may kill more tumor cells.
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose (MTD) of imatinib mesylate after completion of radiation in children with newly diagnosed poor prognosis brainstem gliomas. (Phase I, strata I closed to accrual as of 5/28/04.) II. Determine the maximum tolerated dose (MTD) of imatinib mesylate in children with recurrent high-grade intracranial glioma stratified according to the use of enzyme-inducing anticonvulsant drugs (EIACDs). (Phase I, strata IIA and IIB closed to accrual as of 8/15/03 and 8/15/04, respectively) III. Determine the safety and efficacy of this drug in patients with newly diagnosed diffuse intrinsic brainstem gliomas. (Phase II)
SECONDARY OBJECTIVES:
I. Explore neuroimaging and biological correlatives of therapeutic activity of this regimen in these patients. (Phase I, all strata closed to accrual as of 8/15/04) II. Determine the pharmacokinetics of these regimens in these patients overall and by enzyme-inducing anticonvulsant drugs (EIACDs) (Phase I, all strata closed to accrual as of 8/15/04.) III. Estimate the progression-free survival (PFS) and overall survival (OS) of newly diagnosed diffuse intrinsic brainstem gliomas treated with this drug. (Phase I and II)
OUTLINE: This is a phase I dose-escalation, multicenter study followed by a phase II. Patients are stratified according to tumor type (newly diagnosed intrinsic brainstem glioma vs recurrent/refractory intracranial high-grade glioma). Patients in stratum II (phase I only) are further stratified according to concurrent use of enzyme-inducing anticonvulsant drugs (EIACDs) (yes vs no). Patients are assigned to one of three strata in the phase I study.
Phase I
Cohorts of 2-3 patients receive escalating doses of imatinib mesylate until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which it is estimated that 20% of patients will experience dose-limiting toxicity. MTDs are independently estimated in each strata. For stratum I, newly diagnosed brain stem gliomas, the dose level which at least 5 of 6 patients experience no dose-limiting toxicity will be the dose used in the efficacy and safety phase (phase II).
Phase II: (Open to accrual as of 5/28/04.)
Patients enrolled in the phase I portion and not treated at the MTD are to be followed for the shortest of 1) three months after the last protocol based treatment or 2) the date other therapy is initiated. Stratum I patients treated at the MTD in the phase I portion and all patients in the phase II portion of the study are to be followed until death or withdrawal from the study
PROJECTED ACCRUAL: Approximately 140 patients will be accrued for this study within 2 years.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Imatinib mesylate | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| imatinib mesylate | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants in Phase I Stratum I With Dose Limiting Toxicities (DLT) Observed During First 8 Weeks (Courses 1 and 2) of Imatinib Therapy | The dose limiting toxicity (DLT) analysis population consists of phase I stratum I participants who developed DLT during the maximum tolerated dose (MTD) estimation period (course 1 and 2) or who completed the MTD estimation period (courses 1 and 2) without DLTs. DLTs observed during courses 1 and 2 were used to estimate the MTD. The estimated MTD based on the 23 participants who either had a DLT during course 1 or 2 or completed courses 1 and 2 without DLT is 265 mg/m2/day. | Day 1 of Imatinib Mesylate Therapy to Week 8 |
| Number of Participants in Phase I Stratum II With Dose Limiting Toxicities (DLT) Observed During First 8 Weeks (Courses 1 and 2) of Imatinib Therapy | The dose limiting toxicity (DLT) analysis population consisted of phase I stratum II participants who developed DLT during the maximum tolerated dose (MTD) estimation period (courses 1 and 2) or who completed the MTD estimation period (courses 1 and 2) without DLTs. DLTs observed during courses 1 and 2 were used to estimate the MTD. The estimated MTD based on the DLT analysis population of 20 in stratum IIA was 465 mg/m2/day. An MTD was not established in stratum IIB as no DLTs were observed at the higher dose levels of 620 and 800 mg/m2/day. | Day 1 of Imatinib Mesylate Therapy to Week 8 |
| Median Progression-free Survival (PFS) | Progression-free survival is defined as the interval from initiation of treatment to the earliest of disease progression (tumor increase of 25% over baseline tumor measurement; appearance of new lesion(s); or progressive/worsening neurological status) or death for patients who failed, or to the last date of follow up for patients without failure. | Assessed pre-radiation, before the first dose of imatinib, and then every 8 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Volume FLAIR at Two Weeks After Completion of Radiation | This study attempted to investigate in an exploratory manner the effect of radiation (RT) on changes in various neuroimaging variables in pediatric brainstem gliomas (stratum I). Neuroimaging changes may have some association with outcome (response, survival, etc.). Volume FLAIR is one parameter obtained from standard magnetic resonance imaging (MRI) studies of the brain. Volume FLAIR was obtained at baseline (pre-radiation) and within two (+/- one) weeks after completion of RT. |
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Inclusion Criteria
Age 3 to 21
Performance status of Karnofsky 50-100% OR Lansky 50-100%
Absolute neutrophil count greater than 1,000/mm3
Platelet count greater than 100,000/mm3 (transfusion independent)
Hemoglobin greater than 8 g/dL (transfusion allowed)
Bilirubin no greater than 1.5 times normal for age
SGPT less than 3 times normal for age
Albumin at least 2 g/dL
Creatinine less than 1.5 times normal for age OR Glomerular filtration rate greater than 70 mL/min
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective barrier contraception during and for 6 months after study participation
Stratum I
Stratum II
Exclusion Criteria
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| Name | Affiliation | Role |
|---|---|---|
| Ian F. Pollack, MD | University of Pittsburgh | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UCSF Comprehensive Cancer Center | San Francisco | California | 94143 | United States | ||
| Children's National Medical Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 18425516 | Result | Williams G, Fahey FH, Treves ST, Kocak M, Pollack IF, Boyett JM, Kun LE, Poussaint TY. Exploratory evaluation of two-dimensional and three-dimensional methods of FDG PET quantification in pediatric anaplastic astrocytoma: a report from the Pediatric Brain Tumor Consortium (PBTC). Eur J Nucl Med Mol Imaging. 2008 Sep;35(9):1651-8. doi: 10.1007/s00259-008-0780-7. Epub 2008 Apr 19. | |
| 17293590 | Result | Pollack IF, Jakacki RI, Blaney SM, Hancock ML, Kieran MW, Phillips P, Kun LE, Friedman H, Packer R, Banerjee A, Geyer JR, Goldman S, Poussaint TY, Krasin MJ, Wang Y, Hayes M, Murgo A, Weiner S, Boyett JM. Phase I trial of imatinib in children with newly diagnosed brainstem and recurrent malignant gliomas: a Pediatric Brain Tumor Consortium report. Neuro Oncol. 2007 Apr;9(2):145-60. doi: 10.1215/15228517-2006-031. Epub 2007 Feb 9. |
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The intent of the phase I part of the study was to estimate the maximum tolerated dose (MTD) independently in stratum I, in stratum IIA, and in stratum IIB. The estimated MTD from stratum I was the recommended dose for the phase II part. Phase I participants in stratum I who received study drug at the MTD contributed to the phase II objectives.
Participants from PBTC member institutions were enrolled on the phase I component between 09May2001 and 28MAY2004 (stratum I), 15AUG2003 (stratum IIA), and 15AUG2004 (stratum IIB). The phase II component of the study opened on 28MAY2004 and was terminated on 13APR2005 due to poor accrual.
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| ID | Title | Description |
|---|---|---|
| FG000 | Stratum I: Radiation + Imatinib Mesylate | Children with newly diagnosed brainstem gliomas received imatinib twice daily at a starting dose of 200 mg/m2/day. Treatment cycles were 4 weeks (maximum tolerated dose (MTD) estimation period - first 8 weeks) and imatinib was continued for up to 52 weeks in the absence of progression or serious toxicity. Local irradiation (RT) was administered concurrently with imatinib at the initiation of treatment with conventional fractionation at 180 cGy/day fractions, five days per week for six weeks, to a total dose of 5580 cGy. Because of concerns of intratumoral hemorrhage during RT, the protocol was amended (08JAN2003) to enroll patients without evidence of hemorrhage prior to RT and begin imatinib treatment 2 weeks (± 1 week) after completion of RT. Participants enrolled to the phase II part received imatinib at the MTD (from phase I) after RT. Six participants were enrolled on the phase I before the amendment, 29 after the amendment, and 1 on the phase II. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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|
| local irradiation therapy | Radiation |
|
|
| Baseline and two weeks post completion of radiation |
| Peak Concentration (Cmax) | Peak concentration (cmax) is a pharmacokinetic measure defined as the highest concentration of a drug measured after the drug is administered. The cmax of imatinib mesylate on day 1 of course 1 is reported. Two milliliter (0.5 ml for children under the age of 5) blood samples were collected immediately prior to imatinib mesylate administration on Day 1 of Course 1 and at the following timepoints following drug administration: 0.5, 1, 1.5, 2, 4, 10 and 12 hours after the morning dose. | Day 1 of Course 1 |
| Median Overall Survival | Overall Survival (OS) is defined as the interval from initiation of treatment to death or date of last contact for surviving patients. | Assessed before radiation therapy, before the first dose of imatinib, then every 8 weeks. |
| Pre-treatment Basic Fibroblast Growth Factor Values From Urine | This study attempted to investigate in an exploratory manner the effect of biological markers on tumor growth. Basic fibroblast growth factor (bFGF) may play a role in tumor development by helping tumor vessels establish and grow. Urine was collected from participants before treatment to measure the baseline urine bFGF values. | Pre-treatment |
| Pre-treatment Basic Fibroblast Growth Factor Values From Plasma | This study attempted to investigate in an exploratory manner the effect of biological markers on tumor growth. Basic fibroblast growth factor (bFGF) may play a role in tumor development by helping tumor vessels establish and grow. Blood (plasma) was drawn from participants before treatment to measure the baseline plasma bFGF values. | Pre-treatment |
| Pre-treatment Vascular Endothelial Growth Factor From Urine | This study attempted to investigate in an exploratory manner the effect of biological markers on tumor growth. Vascular endothelial growth factor (VEGF) may play a role in tumor development by helping tumor vessels establish and grow. Urine was collected from participants before treatment to measure the baseline urine VEGF values. | Pre-treatment |
| Pre-treatment Vascular Endothelial Growth Factor Values From Plasma | This study attempted to investigate in an exploratory manner the effect of biological markers on tumor growth. Vascular endothelial growth factor (VEGF) may play a role in tumor development by helping tumor vessels establish and grow. Blood (plasma) was drawn from participants before treatment to measure the baseline plasma VEGF values. | Pre-treatment |
| Washington D.C. |
| District of Columbia |
| 20010-2970 |
| United States |
| Children's Memorial Hospital - Chicago | Chicago | Illinois | 60614 | United States |
| Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute | Boston | Massachusetts | 02115 | United States |
| Duke Comprehensive Cancer Center | Durham | North Carolina | 27710 | United States |
| Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19104-4318 | United States |
| Children's Hospital of Pittsburgh | Pittsburgh | Pennsylvania | 15213 | United States |
| St. Jude Children's Research Hospital | Memphis | Tennessee | 38105-2794 | United States |
| Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital | Houston | Texas | 77030-2399 | United States |
| Children's Hospital and Regional Medical Center - Seattle | Seattle | Washington | 98105 | United States |
| FG001 | Stratum IIA: Imatinib Mesylate | Children with recurrent high-grade gliomas not on enzyme-inducing anticonvulsant drugs (EIACDs) received imatinib twice daily at a starting dose of 350 mg/m2/day. Treatment cycles were 4 weeks (maximum tolerated dose (MTD) estimation period - first 4 weeks) and imatinib was continued for up to 52 weeks in the absence of progression or serious toxicity. Study participants did not receive radiation therapy in this stratum. Because of concerns of intratumoral hemorrhage, the protocol was amended (08JAN2003) to extend the MTD estimation period to 8 weeks (courses 1 and 2). Ten participants were enrolled on the phase I before the amendment and 23 after the amendment. |
| FG002 | Stratum IIB: Imatinib Mesylate | Children with recurrent high-grade gliomas on enzyme-inducing anticonvulsant drugs (EIACDs) received imatinib twice daily at a starting dose of 350 mg/m2/day. Treatment cycles were 4 weeks (maximum tolerated dose (MTD) estimation period - first 4 weeks) and imatinib was continued for up to 52 weeks in the absence of progression or serious toxicity. Study participants did not receive radiation therapy in this stratum. Because of concerns of intratumoral hemorrhage, the protocol was amended (08JAN2003) to extend the MTD estimation period to 8 weeks (courses 1 and 2). Eight participants were enrolled on the phase I before the amendment and eight after the amendment. |
| Enrolled in Phase I |
|
| Maximum Tolerated Dose (MTD) Estimation |
|
| Enrolled in Phase II |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Stratum I: Radiation + Imatinib Mesylate | Children with newly diagnosed brainstem gliomas received imatinib twice daily at a starting dose of 200 mg/m2/day. Treatment cycles were 4 weeks (maximum tolerated dose (MTD) estimation period - first 8 weeks) and imatinib was continued for up to 52 weeks in the absence of progression or serious toxicity. Local irradiation (RT) was administered concurrently with imatinib at the initiation of treatment with conventional fractionation at 180 cGy/day fractions, five days per week for six weeks, to a total dose of 5580 cGy. Because of concerns of intratumoral hemorrhage during RT, the protocol was amended (08JAN2003) to enroll patients without evidence of hemorrhage prior to RT and begin imatinib treatment 2 weeks (± 1 week) after completion of RT. Participants enrolled to the phase II part received imatinib at the MTD (from phase I) after RT. Six participants were enrolled on the phase I before the amendment, 29 after the amendment, and 1 on the phase II. |
| BG001 | Stratum IIA: Imatinib Mesylate | Children with recurrent high-grade gliomas not on enzyme-inducing anticonvulsant drugs (EIACDs) received imatinib twice daily at a starting dose of 350 mg/m2/day. Treatment cycles were 4 weeks (maximum tolerated dose (MTD) estimation period - first 4 weeks) and imatinib was continued for up to 52 weeks in the absence of progression or serious toxicity. Study participants did not receive radiation therapy in this stratum. Because of concerns of intratumoral hemorrhage, the protocol was amended (08JAN2003) to extend the MTD estimation period to 8 weeks (courses 1 and 2). Ten participants were enrolled on the phase I before the amendment and 23 after the amendment. |
| BG002 | Stratum IIB: Imatinib Mesylate | Children with recurrent high-grade gliomas on enzyme-inducing anticonvulsant drugs (EIACDs) received imatinib twice daily at a starting dose of 350 mg/m2/day. Treatment cycles were 4 weeks (maximum tolerated dose (MTD) estimation period - first 4 weeks) and imatinib was continued for up to 52 weeks in the absence of progression or serious toxicity. Study participants did not receive radiation therapy in this stratum. Because of concerns of intratumoral hemorrhage, the protocol was amended (08JAN2003) to extend the MTD estimation period to 8 weeks (courses 1 and 2). Eight participants were enrolled on the phase I before the amendment and eight after the amendment. |
| 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, Categorical | Count of Participants | Participants |
| ||||||||||||||||
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | 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 Participants in Phase I Stratum I With Dose Limiting Toxicities (DLT) Observed During First 8 Weeks (Courses 1 and 2) of Imatinib Therapy | The dose limiting toxicity (DLT) analysis population consists of phase I stratum I participants who developed DLT during the maximum tolerated dose (MTD) estimation period (course 1 and 2) or who completed the MTD estimation period (courses 1 and 2) without DLTs. DLTs observed during courses 1 and 2 were used to estimate the MTD. The estimated MTD based on the 23 participants who either had a DLT during course 1 or 2 or completed courses 1 and 2 without DLT is 265 mg/m2/day. | Per protocol, participants included phase I stratum I participants who developed dose-limiting toxicities during the maximum tolerated dose (MTD) estimation period (courses 1 and 2) or who completed the MTD estimation period (courses 1 and 2) without dose-limiting toxicities. | Posted | Number | Participants | Day 1 of Imatinib Mesylate Therapy to Week 8 |
|
|
| ||||||||||||||||||||||||||
| Primary | Number of Participants in Phase I Stratum II With Dose Limiting Toxicities (DLT) Observed During First 8 Weeks (Courses 1 and 2) of Imatinib Therapy | The dose limiting toxicity (DLT) analysis population consisted of phase I stratum II participants who developed DLT during the maximum tolerated dose (MTD) estimation period (courses 1 and 2) or who completed the MTD estimation period (courses 1 and 2) without DLTs. DLTs observed during courses 1 and 2 were used to estimate the MTD. The estimated MTD based on the DLT analysis population of 20 in stratum IIA was 465 mg/m2/day. An MTD was not established in stratum IIB as no DLTs were observed at the higher dose levels of 620 and 800 mg/m2/day. | Per protocol, participants included phase I stratum II participants who developed dose-limiting toxicities (DLT) during the maximum tolerated dose (MTD) estimation period (courses 1 and 2) or who completed the MTD estimation period (courses 1 and 2) without DLTs. | Posted | Number | Participants | Day 1 of Imatinib Mesylate Therapy to Week 8 |
| ||||||||||||||||||||||||||||
| Primary | Median Progression-free Survival (PFS) | Progression-free survival is defined as the interval from initiation of treatment to the earliest of disease progression (tumor increase of 25% over baseline tumor measurement; appearance of new lesion(s); or progressive/worsening neurological status) or death for patients who failed, or to the last date of follow up for patients without failure. | Per protocol, 40 participants who received at least one dose of drug were needed for this objective. The analysis population consists of stratum I participants enrolled at the maximum tolerated dose (phase 1) and the participants enrolled to the phase II part. The study was terminated because of poor accrual and the objective was not met. | Posted | Assessed pre-radiation, before the first dose of imatinib, and then every 8 weeks |
| ||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Volume FLAIR at Two Weeks After Completion of Radiation | This study attempted to investigate in an exploratory manner the effect of radiation (RT) on changes in various neuroimaging variables in pediatric brainstem gliomas (stratum I). Neuroimaging changes may have some association with outcome (response, survival, etc.). Volume FLAIR is one parameter obtained from standard magnetic resonance imaging (MRI) studies of the brain. Volume FLAIR was obtained at baseline (pre-radiation) and within two (+/- one) weeks after completion of RT. | The analysis population consists of Stratum I patients enrolled who had both pre and post radiation (RT) volume FLAIR measures. Stratum II participants did not receive RT and thus were not included. | Posted | Mean | Full Range | cubic centimeters | Baseline and two weeks post completion of radiation |
| |||||||||||||||||||||||||||
| Secondary | Peak Concentration (Cmax) | Peak concentration (cmax) is a pharmacokinetic measure defined as the highest concentration of a drug measured after the drug is administered. The cmax of imatinib mesylate on day 1 of course 1 is reported. Two milliliter (0.5 ml for children under the age of 5) blood samples were collected immediately prior to imatinib mesylate administration on Day 1 of Course 1 and at the following timepoints following drug administration: 0.5, 1, 1.5, 2, 4, 10 and 12 hours after the morning dose. | The analysis population consists of participants who enrolled at the maximum tolerated dose (MTD) of the phase I component and who submitted day 1 course 1 samples for the PK studies. An MTD was not estimated in stratum IIB. For this stratum, reported are values at the stratum IIA MTD to allow comparison. | Posted | Mean | Full Range | µg/ml | Day 1 of Course 1 |
| |||||||||||||||||||||||||||
| Secondary | Median Overall Survival | Overall Survival (OS) is defined as the interval from initiation of treatment to death or date of last contact for surviving patients. | The analysis population consists of the stratum I participants who received imatinib mesylate at or above the maximum tolerated dose. The median survival reported is based on these 20 participants. | Posted | Median | 95% Confidence Interval | Days | Assessed before radiation therapy, before the first dose of imatinib, then every 8 weeks. |
| |||||||||||||||||||||||||||
| Secondary | Pre-treatment Basic Fibroblast Growth Factor Values From Urine | This study attempted to investigate in an exploratory manner the effect of biological markers on tumor growth. Basic fibroblast growth factor (bFGF) may play a role in tumor development by helping tumor vessels establish and grow. Urine was collected from participants before treatment to measure the baseline urine bFGF values. | Per protocol, the analysis population consists of participants treated on the phase I component who submitted pre-treatment urine samples for the biomarker study. | Posted | Mean | Standard Deviation | pg/ml | Pre-treatment |
| |||||||||||||||||||||||||||
| Secondary | Pre-treatment Basic Fibroblast Growth Factor Values From Plasma | This study attempted to investigate in an exploratory manner the effect of biological markers on tumor growth. Basic fibroblast growth factor (bFGF) may play a role in tumor development by helping tumor vessels establish and grow. Blood (plasma) was drawn from participants before treatment to measure the baseline plasma bFGF values. | Per protocol, the analysis population consists of participants treated on the phase I component who submitted pre-treatment blood samples for the biomarker study. | Posted | Mean | Standard Deviation | pg/ml | Pre-treatment |
| |||||||||||||||||||||||||||
| Secondary | Pre-treatment Vascular Endothelial Growth Factor From Urine | This study attempted to investigate in an exploratory manner the effect of biological markers on tumor growth. Vascular endothelial growth factor (VEGF) may play a role in tumor development by helping tumor vessels establish and grow. Urine was collected from participants before treatment to measure the baseline urine VEGF values. | Per protocol, the analysis population consists of participants treated on the phase I component who submitted pre-treatment urine samples for the biomarker study. | Posted | Mean | Standard Deviation | pg/ml | Pre-treatment |
| |||||||||||||||||||||||||||
| Secondary | Pre-treatment Vascular Endothelial Growth Factor Values From Plasma | This study attempted to investigate in an exploratory manner the effect of biological markers on tumor growth. Vascular endothelial growth factor (VEGF) may play a role in tumor development by helping tumor vessels establish and grow. Blood (plasma) was drawn from participants before treatment to measure the baseline plasma VEGF values. | Per protocol, the analysis population consists of participants treated on the phase I component who submitted pre-treatment blood samples for the biomarker study. | Posted | Mean | Standard Error | pg/ml | Pre-treatment |
|
Adverse events were assessed weekly during the first four weeks (course 1), every 2 weeks during the next 2 courses (8 weeks total), every 4 weeks for all subsequent courses (up to 13 courses), and through 30 days following the end of treatment.
Assessments were made routinely for all patients per the schedule of clinical and laboratory assessments outlined in the protocol.
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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 | Stratum I: Radiation + Imatinib Mesylate | Children with newly diagnosed brainstem gliomas received imatinib twice daily at a starting dose of 200 mg/m2/day. Treatment cycles were 4 weeks (maximum tolerated dose (MTD) estimation period - first 8 weeks) and imatinib was continued for up to 52 weeks in the absence of progression or serious toxicity. Local irradiation (RT) was administered concurrently with imatinib at the initiation of treatment with conventional fractionation at 180 cGy/day fractions, five days per week for six weeks, to a total dose of 5580 cGy. Because of concerns of intratumoral hemorrhage during RT, the protocol was amended (08JAN2003) to enroll patients without evidence of hemorrhage prior to RT and begin imatinib treatment 2 weeks (± 1 week) after completion of RT. Participants enrolled to the phase II part received imatinib at the MTD (from phase I) after RT. Six participants were enrolled on the phase I before the amendment, 29 after the amendment, and 1 on the phase II. | 13 | 36 | 33 | 36 | ||
| EG001 | Stratum IIA: Imatinib Mesylate | Children with recurrent high-grade gliomas not on enzyme-inducing anticonvulsant drugs (EIACDs) received imatinib twice daily at a starting dose of 350 mg/m2/day. Treatment cycles were 4 weeks (maximum tolerated dose (MTD) estimation period - first 4 weeks) and imatinib was continued for up to 52 weeks in the absence of progression or serious toxicity. Study participants did not receive radiation therapy in this stratum. Because of concerns of intratumoral hemorrhage, the protocol was amended (08JAN2003) to extend the MTD estimation period to 8 weeks (courses 1 and 2). Ten participants were enrolled on the phase I before the amendment and 23 after the amendment. | 13 | 33 | 31 | 33 | ||
| EG002 | Stratum IIB: Imatinib Mesylate | Children with recurrent high-grade gliomas on enzyme-inducing anticonvulsant drugs (EIACDs) received imatinib twice daily at a starting dose of 350 mg/m2/day. Treatment cycles were 4 weeks (maximum tolerated dose (MTD) estimation period - first 4 weeks) and imatinib was continued for up to 52 weeks in the absence of progression or serious toxicity. Study participants did not receive radiation therapy in this stratum. Because of concerns of intratumoral hemorrhage, the protocol was amended (08JAN2003) to extend the MTD estimation period to 8 weeks (courses 1 and 2). Eight participants were enrolled on the phase I before the amendment and eight after the amendment. | 5 | 16 | 14 | 16 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain or cramping | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Bicarbonate | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
| |
| CNS hemorrhage/bleeding | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Confusion | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Creatinine | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Dehydration | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Depressed level of consciousness | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Diarrhea without colostomy | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Edema | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Fatigue | General disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Fever (in the absence of neutropenia) | General disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Headache | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Hematemesis | Vascular disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Hematuria | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Hemoglobin (Hgb) | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Hyperglycemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Hypoalbuminemia | Hepatobiliary disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Hypocalcemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Hypokalemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Hyponatremia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Hypophosphatemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Incontinence | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Infection without neutropenia | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
| |
| Inpatient Hospital Days | General disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Leukocytes (total WBC) | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Melena/GI bleeding | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Memory loss | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Metabolic/Laboratory- Other | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Musculoskeletal - Other | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Neurology - Other | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Neuropathy - Motor | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Neuropathy - cranial | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Neuropathy - sensory | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Neutrophils/granulocytes (ANC/AGC) | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Pain - other | General disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Pigmentation changes | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Platelets | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Pleural effusion (non-malignant) | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Rash/desquamation | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Renal/Genitourinary - Other | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Seizures | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Speech impairment | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Thrombosis/embolism | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Tremor | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain or cramping | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Alkaline phosphatase | Investigations | CTCAE (3.0) | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Anorexia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Arthralgia (joint pain) | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Ataxia (incoordination) | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Bicarbonate | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Bilirubin | Hepatobiliary disorders | CTCAE (3.0) | Systematic Assessment |
| |
| CNS hemorrhage/bleeding | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Cognitive/disturbance/learning problems | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Conjunctivitis | Eye disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Constitutional symptoms - Other | General disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Creatinine | Investigations | CTCAE (3.0) | Systematic Assessment |
| |
| Cushingnoid appearance | Endocrine disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Depressed level of consciousness | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Dermatology/skin -Other | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Diarrhea without colostomy | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Dizziness/light-headedness | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Dyspepsia/heartburn | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Dysphagia, esophagitis, odynophagia (painful swallowing) | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Dysuria | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Earache (otalgia) | Ear and labyrinth disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Edema | Vascular disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
| |
| External auditory canal | Ear and labyrinth disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Fatigue | General disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Fever (in the absence of neutropenia) | General disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
| |
| GGT | Investigations | CTCAE (3.0) | Systematic Assessment |
| |
| Gastrointestinal-Other | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Headache | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Hemoglobin | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Hepatic-Other | Hepatobiliary disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Hypercholesterolemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Hyperglycemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Hyperkalemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Hypermagnesemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Hypernatremia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Hypertriglyceridemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Hyperuricemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Hypoalbuminemia | Hepatobiliary disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Hypocalcemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Hypoglycemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Hypokalemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Hypomagnesemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Hyponatremia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Hypophosphatemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Incontinence | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Infection without neutropenia | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
| |
| Infection/Febrile Neutropenia-Other | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
| |
| Inner ear/hearing | Ear and labyrinth disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Irritability (<3 years of age) | General disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Leukocytes | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Metabolic/Laboratory - Other | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Mood alteration - anxiety, agitation | Psychiatric disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Mood alteration - depression | Psychiatric disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Muscle weakness | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Musculoskeletal-Other | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Myalgia (muscle pain) | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Neurology - other | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Neuropathic pain | General disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Neuropathy - cranial | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Neuropathy - motor | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Neuropathy - sensory | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Neutrophils/granulocytes | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Nystagmus | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Ocular/Visual - Other | Eye disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Pain - other | General disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Personality/behavioral | Psychiatric disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Platelets | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Pulmonary-Other | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Rash/desquamation | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Renal/Genitourinary-Other | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment |
| |
| SGOT (AST) | Hepatobiliary disorders | CTCAE (3.0) | Systematic Assessment |
| |
| SGPT (ALT) | Hepatobiliary disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Seizure(s) | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Speech impairment | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Stomatitis/pharyngitis | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Transfusions: pRBCs | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Tremor | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Urinary frequency/urgency | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Urinary retention | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Vision - blurred vision | Eye disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Vision - double vision | Eye disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Weight gain | Investigations | CTCAE (3.0) | Systematic Assessment |
| |
| Weight loss | Investigations | CTCAE (3.0) | Systematic Assessment |
| |
| Rash/Dermatitis | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
The phase II component of the trial was terminated because of poor accrual. Only one patient enrolled to the phase II component and did not receive the investigational drug.
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pediatric Brain Tumor Consortium (James M. Boyett, Ph.D) | Pediatric Brain Tumor Consortium | 901-595-4986 | james.boyett@stjude.org |
| ID | Term |
|---|---|
| D016543 | Central Nervous System Neoplasms |
| D001254 | Astrocytoma |
| ID | Term |
|---|---|
| D009423 | Nervous System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D009422 | Nervous System Diseases |
| D005910 | Glioma |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
Not provided
Not provided
| ID | Term |
|---|---|
| D000068877 | Imatinib Mesylate |
| ID | Term |
|---|---|
| D001549 | Benzamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D001565 | Benzoates |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D010879 | Piperazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011743 | Pyrimidines |
Not provided
Not provided
| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|
| OG001 | Stratum IIB: Imatinib Mesylate | Children with recurrent high-grade gliomas on enzyme-inducing anticonvulsant drugs (EIACDs) received imatinib twice daily at a starting dose of 350 mg/m2/day. Treatment cycles were 4 weeks (maximum tolerated dose (MTD) estimation period - first 4 weeks) and imatinib was continued for up to 52 weeks in the absence of progression or serious toxicity. Study participants did not receive radiation therapy in this stratum. Because of concerns of intratumoral hemorrhage, the protocol was amended (08JAN2003) to extend the MTD estimation period to 8 weeks (courses 1 and 2). Eight participants were enrolled on the phase I before the amendment and eight after the amendment. |
|
|
|
|
|
| OG001 | Stratum IIA: Imatinib Mesylate | Children with recurrent high-grade gliomas not on enzyme-inducing anticonvulsant drugs (EIACDs) received imatinib twice daily at a starting dose of 350 mg/m2/day. Treatment cycles were 4 weeks (maximum tolerated dose (MTD) estimation period - first 4 weeks) and imatinib was continued for up to 52 weeks in the absence of progression or serious toxicity. Study participants did not receive radiation therapy in this stratum. Because of concerns of intratumoral hemorrhage, the protocol was amended (08JAN2003) to extend the MTD estimation period to 8 weeks (courses 1 and 2). Ten participants were enrolled on the phase I before the amendment and 23 after the amendment. |
| OG002 | Stratum IIB: Imatinib Mesylate | Children with recurrent high-grade gliomas on enzyme-inducing anticonvulsant drugs (EIACDs) received imatinib twice daily at a starting dose of 350 mg/m2/day. Treatment cycles were 4 weeks (maximum tolerated dose (MTD) estimation period - first 4 weeks) and imatinib was continued for up to 52 weeks in the absence of progression or serious toxicity. Study participants did not receive radiation therapy in this stratum. Because of concerns of intratumoral hemorrhage, the protocol was amended (08JAN2003) to extend the MTD estimation period to 8 weeks (courses 1 and 2). Eight participants were enrolled on the phase I before the amendment and eight after the amendment. |
|
|
| Units | Counts |
|---|
| Participants |
|
|
| OG001 |
| Stratum IIA: Imatinib Mesylate |
Children with recurrent high-grade gliomas not on enzyme-inducing anticonvulsant drugs (EIACDs) received imatinib twice daily at a starting dose of 350 mg/m2/day. Treatment cycles were 4 weeks (maximum tolerated dose (MTD) estimation period - first 4 weeks) and imatinib was continued for up to 52 weeks in the absence of progression or serious toxicity. Study participants did not receive radiation therapy in this stratum. Because of concerns of intratumoral hemorrhage, the protocol was amended (08JAN2003) to extend the MTD estimation period to 8 weeks (courses 1 and 2). Ten participants were enrolled on the phase I before the amendment and 23 after the amendment. |
| OG002 | Stratum IIB: Imatinib Mesylate | Children with recurrent high-grade gliomas on enzyme-inducing anticonvulsant drugs (EIACDs) received imatinib twice daily at a starting dose of 350 mg/m2/day. Treatment cycles were 4 weeks (maximum tolerated dose (MTD) estimation period - first 4 weeks) and imatinib was continued for up to 52 weeks in the absence of progression or serious toxicity. Study participants did not receive radiation therapy in this stratum. Because of concerns of intratumoral hemorrhage, the protocol was amended (08JAN2003) to extend the MTD estimation period to 8 weeks (courses 1 and 2). Eight participants were enrolled on the phase I before the amendment and eight after the amendment. |
|
|
| OG001 | Stratum IIA: Imatinib Mesylate | Children with recurrent high-grade gliomas not on enzyme-inducing anticonvulsant drugs (EIACDs) received imatinib twice daily at a starting dose of 350 mg/m2/day. Treatment cycles were 4 weeks (maximum tolerated dose (MTD) estimation period - first 4 weeks) and imatinib was continued for up to 52 weeks in the absence of progression or serious toxicity. Study participants did not receive radiation therapy in this stratum. Because of concerns of intratumoral hemorrhage, the protocol was amended (08JAN2003) to extend the MTD estimation period to 8 weeks (courses 1 and 2). Ten participants were enrolled on the phase I before the amendment and 23 after the amendment. |
| OG002 | Stratum IIB: Imatinib Mesylate | Children with recurrent high-grade gliomas on enzyme-inducing anticonvulsant drugs (EIACDs) received imatinib twice daily at a starting dose of 350 mg/m2/day. Treatment cycles were 4 weeks (maximum tolerated dose (MTD) estimation period - first 4 weeks) and imatinib was continued for up to 52 weeks in the absence of progression or serious toxicity. Study participants did not receive radiation therapy in this stratum. Because of concerns of intratumoral hemorrhage, the protocol was amended (08JAN2003) to extend the MTD estimation period to 8 weeks (courses 1 and 2). Eight participants were enrolled on the phase I before the amendment and eight after the amendment. |
|
|
| OG001 | Stratum IIA: Imatinib Mesylate | Children with recurrent high-grade gliomas not on enzyme-inducing anticonvulsant drugs (EIACDs) received imatinib twice daily at a starting dose of 350 mg/m2/day. Treatment cycles were 4 weeks (maximum tolerated dose (MTD) estimation period - first 4 weeks) and imatinib was continued for up to 52 weeks in the absence of progression or serious toxicity. Study participants did not receive radiation therapy in this stratum. Because of concerns of intratumoral hemorrhage, the protocol was amended (08JAN2003) to extend the MTD estimation period to 8 weeks (courses 1 and 2). Ten participants were enrolled on the phase I before the amendment and 23 after the amendment. |
| OG002 | Stratum IIB: Imatinib Mesylate | Children with recurrent high-grade gliomas on enzyme-inducing anticonvulsant drugs (EIACDs) received imatinib twice daily at a starting dose of 350 mg/m2/day. Treatment cycles were 4 weeks (maximum tolerated dose (MTD) estimation period - first 4 weeks) and imatinib was continued for up to 52 weeks in the absence of progression or serious toxicity. Study participants did not receive radiation therapy in this stratum. Because of concerns of intratumoral hemorrhage, the protocol was amended (08JAN2003) to extend the MTD estimation period to 8 weeks (courses 1 and 2). Eight participants were enrolled on the phase I before the amendment and eight after the amendment. |
|
|
| OG001 | Stratum IIA: Imatinib Mesylate | Children with recurrent high-grade gliomas not on enzyme-inducing anticonvulsant drugs (EIACDs) received imatinib twice daily at a starting dose of 350 mg/m2/day. Treatment cycles were 4 weeks (maximum tolerated dose (MTD) estimation period - first 4 weeks) and imatinib was continued for up to 52 weeks in the absence of progression or serious toxicity. Study participants did not receive radiation therapy in this stratum. Because of concerns of intratumoral hemorrhage, the protocol was amended (08JAN2003) to extend the MTD estimation period to 8 weeks (courses 1 and 2). Ten participants were enrolled on the phase I before the amendment and 23 after the amendment. |
| OG002 | Stratum IIB: Imatinib Mesylate | Children with recurrent high-grade gliomas on enzyme-inducing anticonvulsant drugs (EIACDs) received imatinib twice daily at a starting dose of 350 mg/m2/day. Treatment cycles were 4 weeks (maximum tolerated dose (MTD) estimation period - first 4 weeks) and imatinib was continued for up to 52 weeks in the absence of progression or serious toxicity. Study participants did not receive radiation therapy in this stratum. Because of concerns of intratumoral hemorrhage, the protocol was amended (08JAN2003) to extend the MTD estimation period to 8 weeks (courses 1 and 2). Eight participants were enrolled on the phase I before the amendment and eight after the amendment. |
|
|