Brain and Central Nervous System Tumors
Conditions
Keywords
childhood central nervous system germ cell tumor, childhood high-grade cerebral astrocytoma, untreated childhood brain stem glioma, recurrent childhood brain stem glioma, recurrent childhood cerebral astrocytoma
Brief summary
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.
Detailed description
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 * Stratum I (newly diagnosed brainstem glioma): Patients undergo radiotherapy once daily five days a week for 6 weeks. Beginning 1-3 weeks after completion of radiotherapy, patients without evidence of intratumoral bleed receive oral imatinib mesylate twice daily. Imatinib mesylate treatment repeats every 4 weeks for up to 13 courses in the absence of disease progression or unacceptable toxicity. (Closed to accrual as of 5/28/04.) * Stratum II A (recurrent or refractory high-grade intracranial gliomas/no concurrent EIACDs): Patients receive imatinib mesylate as in stratum I. (Closed to accrual as of 8/15/03.) * Stratum II B (recurrent or refractory high-grade intracranial gliomas and concurrent EIACDs): Patients receive imatinib mesylate as in stratum I. (Closed to accrual as of 8/15/04.) 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.) * Stratum I only: Patients undergo radiotherapy as in phase I. Patients receive imatinib mesylate at the MTD established in phase I. 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.
Interventions
DRUGimatinib mesylate
* Phase 1 Stratum I: Starting dose level of 350 mg/m2/day every 28 days X 13 courses (dose escalation) * Phase I Stratum IIA: Starting dose level of 465 mg/m2/day every 28 days X 13 courses (dose escalation) * Phase I Stratum IIB: Starting dose level of 465 mg/m2/day every 28 days X 13 courses (dose escalation) * Phase II: Phase I Stratum I determined dose (Maximum tolerated dose) every 28 days X 13 courses.
RADIATIONlocal irradiation therapy
* Phase I Stratum I: Total dose of 5580 cGy using conventional or conformal volume-based delivery techniques once daily, 5 days/week for six weeks prior to receiving imatinib. * Phase II: Total dose of 5580 cGy using conventional or conformal volume-based delivery techniques once daily, 5 days/week for six weeks prior to receiving imatinib.
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 21 Years
Healthy volunteers
No
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 * Newly diagnosed diffuse intrinsic brainstem malignant glioma * No disseminated disease * No radiographic evidence of intratumoral hemorrhage before or during radiotherapy * No prior chemotherapy (beyond routine corticosteroids) * No prior irradiation * Must not be receiving enzyme-inducing anticonvulsant drugs * Stratum II * Histologically confirmed recurrent or refractory anaplastic astrocytoma, glioblastoma multiforme, or other high-grade glioma (including recurrent brain stem glioma * No intratumoral hemorrhage unrelated to prior surgical procedure * No myelosuppressive chemotherapy within 3 weeks (6 weeks if a nitrosourea agent) of study entry * No prior imatinib mesylate * At least 3 months since prior craniospinal radiotherapy (18 Gy or more) * At least 8 weeks since prior local radiotherapy to primary tumor * At least 2 weeks since prior focal radiotherapy for symptomatic * At least 3 months since prior bone marrow transplantation * Neurological deficits allowed if stable for at least 1 week prior to study
Exclusion criteria
* Receiving other anticancer or experimental drug therapy. * Ongoing uncontrolled infection. * Significant cardiac, hepatic, gastrointestinal, renal, pulmonary, or psychiatric disease. * Deep venous or arterial thrombosis within 6 weeks of registration. * Taking warfarin. * Newly diagnosed diffuse intrinsic brainstem malignant glioma with disseminated disease (stratum I) * Intratumoral hemorrhage
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Day 1 of Imatinib Mesylate Therapy to Week 8 | 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. |
| 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 | Day 1 of Imatinib Mesylate Therapy to Week 8 | 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. |
| Median Progression-free Survival (PFS) | Assessed pre-radiation, before the first dose of imatinib, and then every 8 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pre-treatment Basic Fibroblast Growth Factor Values From Urine | Pre-treatment | 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 Basic Fibroblast Growth Factor Values From Plasma | Pre-treatment | 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. |
| Change From Baseline in Volume FLAIR at Two Weeks After Completion of Radiation | Baseline and two weeks post 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. |
| Pre-treatment Vascular Endothelial Growth Factor Values From Plasma | Pre-treatment | 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 Vascular Endothelial Growth Factor From Urine | Pre-treatment | 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. |
| Peak Concentration (Cmax) | Day 1 of Course 1 | 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. |
| Median Overall Survival | Assessed before radiation therapy, before the first dose of imatinib, then every 8 weeks. | Overall Survival (OS) is defined as the interval from initiation of treatment to death or date of last contact for surviving patients. |
Countries
United States
Participant flow
Recruitment details
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.
Pre-assignment details
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 by arm
| Arm | Count |
|---|---|
| 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. | 36 |
| 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. | 33 |
| 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. | 16 |
| Total | 85 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 10 | 5 | 2 |
| Overall Study | Death | 0 | 1 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 1 |
| Overall Study | Progressive Disease | 15 | 19 | 12 |
| Overall Study | Protocol Violation | 1 | 1 | 0 |
| Overall Study | Punctate hemmorrhage post RT | 2 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 7 | 7 | 1 |
Baseline characteristics
| Characteristic | Stratum IIA: Imatinib Mesylate | Stratum IIB: Imatinib Mesylate | Stratum I: Radiation + Imatinib Mesylate | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 30 Participants | 15 Participants | 36 Participants | 81 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 1 Participants | 0 Participants | 4 Participants |
| Age, Continuous | 10.9 years STANDARD_DEVIATION 5.4 | 14.1 years STANDARD_DEVIATION 4.7 | 8.05 years STANDARD_DEVIATION 4.3 | 10.3 years STANDARD_DEVIATION 5.3 |
| Region of Enrollment United States | 33 participants | 16 participants | 36 participants | 85 participants |
| Sex: Female, Male Female | 20 Participants | 9 Participants | 18 Participants | 47 Participants |
| Sex: Female, Male Male | 13 Participants | 7 Participants | 18 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 33 / 36 | 31 / 33 | 14 / 16 |
| serious Total, serious adverse events | 13 / 36 | 13 / 33 | 5 / 16 |
Outcome results
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.
Time frame: Assessed pre-radiation, before the first dose of imatinib, and then every 8 weeks
Population: 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.
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.
Time frame: Day 1 of Imatinib Mesylate Therapy to Week 8
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stratum I: Radiation + Imatinib Mesylate | 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 | 2 Participants |
| Stratum IIB: Imatinib Mesylate | 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 | 0 Participants |
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.
Time frame: Day 1 of Imatinib Mesylate Therapy to Week 8
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stratum I: Radiation + Imatinib Mesylate | 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 | 5 Participants |
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.
Time frame: Baseline and two weeks post completion of radiation
Population: 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.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Stratum I: Radiation + Imatinib Mesylate | Change From Baseline in Volume FLAIR at Two Weeks After Completion of Radiation | 7.62 cubic centimeters |
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.
Time frame: Assessed before radiation therapy, before the first dose of imatinib, then every 8 weeks.
Population: 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.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Stratum I: Radiation + Imatinib Mesylate | Median Overall Survival | 324.5 Days | 95% Confidence Interval 8.7 |
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.
Time frame: Day 1 of Course 1
Population: 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.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Stratum I: Radiation + Imatinib Mesylate | Peak Concentration (Cmax) | 1.3 µg/ml |
| Stratum IIB: Imatinib Mesylate | Peak Concentration (Cmax) | 2.6 µg/ml |
| Stratum IIB: Imatinib Mesylate | Peak Concentration (Cmax) | 1.3 µg/ml |
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.
Time frame: Pre-treatment
Population: Per protocol, the analysis population consists of participants treated on the phase I component who submitted pre-treatment blood samples for the biomarker study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Stratum I: Radiation + Imatinib Mesylate | Pre-treatment Basic Fibroblast Growth Factor Values From Plasma | 8.69 pg/ml | Standard Deviation 7.16 |
| Stratum IIB: Imatinib Mesylate | Pre-treatment Basic Fibroblast Growth Factor Values From Plasma | 32.3 pg/ml | Standard Deviation 64.5 |
| Stratum IIB: Imatinib Mesylate | Pre-treatment Basic Fibroblast Growth Factor Values From Plasma | 11.3 pg/ml | Standard Deviation 12.2 |
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.
Time frame: Pre-treatment
Population: Per protocol, the analysis population consists of participants treated on the phase I component who submitted pre-treatment urine samples for the biomarker study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Stratum I: Radiation + Imatinib Mesylate | Pre-treatment Basic Fibroblast Growth Factor Values From Urine | 5665 pg/ml | Standard Deviation 4006 |
| Stratum IIB: Imatinib Mesylate | Pre-treatment Basic Fibroblast Growth Factor Values From Urine | 10322 pg/ml | Standard Deviation 14443 |
| Stratum IIB: Imatinib Mesylate | Pre-treatment Basic Fibroblast Growth Factor Values From Urine | 5312 pg/ml | Standard Deviation 6262 |
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.
Time frame: Pre-treatment
Population: Per protocol, the analysis population consists of participants treated on the phase I component who submitted pre-treatment urine samples for the biomarker study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Stratum I: Radiation + Imatinib Mesylate | Pre-treatment Vascular Endothelial Growth Factor From Urine | 79 pg/ml | Standard Deviation 69.9 |
| Stratum IIB: Imatinib Mesylate | Pre-treatment Vascular Endothelial Growth Factor From Urine | 86.1 pg/ml | Standard Deviation 93.9 |
| Stratum IIB: Imatinib Mesylate | Pre-treatment Vascular Endothelial Growth Factor From Urine | 45.3 pg/ml | Standard Deviation 38 |
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.
Time frame: Pre-treatment
Population: Per protocol, the analysis population consists of participants treated on the phase I component who submitted pre-treatment blood samples for the biomarker study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Stratum I: Radiation + Imatinib Mesylate | Pre-treatment Vascular Endothelial Growth Factor Values From Plasma | 119.9 pg/ml | Standard Error 168.5 |
| Stratum IIB: Imatinib Mesylate | Pre-treatment Vascular Endothelial Growth Factor Values From Plasma | 155.2 pg/ml | Standard Error 229.7 |
| Stratum IIB: Imatinib Mesylate | Pre-treatment Vascular Endothelial Growth Factor Values From Plasma | 78.2 pg/ml | Standard Error 59.4 |