Brief Summary
RATIONALE: Modafinil may help improve memory, attention, and fatigue caused by cancer treatment.
PURPOSE: This phase II randomized trial studies how well modafinil works in treating children with memory and attention problems caused by cancer treatment for a brain tumor.
PURPOSE: This phase II randomized trial studies how well modafinil works in treating children with memory and attention problems caused by cancer treatment for a brain tumor.
Brief Title
Modafinil in Treating Children With Memory and Attention Problems Caused by Cancer Treatment for a Brain Tumor
Detailed Description
OBJECTIVES:
Primary
* Determine whether a 6-week drug trial of modafinil, compared to placebo, is associated with improvement in neurocognitive function as defined by direct assessment of attention in children with cognitive impairment after treatment for a primary brain tumor.
Secondary
* Determine whether modafinil, compared to placebo, is associated with improved executive function, as assessed using the BRIEF executive function and hippocampal learning and executive function tasks from the CogState battery. Determine whether modafinil, compared to placebo, is associated with improved attention, as assessed by the Conners' (3rd Edition) 3 Parent Rating Scale (CPRS-3) - Short Form.
* Determine whether modafinil, compared to placebo, is associated with reduced fatigue as assessed using the PedsQL Multidimensional Fatigue Scale.
* Evaluate the safety of modafinil in this population.
OUTLINE: This is a multicenter study. Participants are randomized to 1 of 2 treatment arms.
* Arm I: Participants receive modafinil orally (PO) once daily (QD) on days 1-42.
* Arm II: Participants receive placebo PO QD on days 1-42. Participants complete a semi-automated, computerized cognitive-testing system (CogState) designed to assess psychomotor, attention/vigilance, memory, and other components of executive function by presenting different tasks, each with its own set of rules, at baseline and after completion of study therapy. Participants also complete the PedsQL Multidimensional Fatigue Scale (Peds QL-MFS).
Parents or legal guardians complete the PedsQL-MFS, the Conners Parent Reported Scale (CPR-3), and the Behavior Rating Inventory of Executive Function (BRIEF) at baseline and after completion of study therapy.
Clinical and/or research staff administer the Systematic Assessment for Treatment Emergency Events (SAFTEE), a semi-structured interview designed to elicit adverse events, at baseline and periodically during study.
After completion of study therapy, participants are followed up for 30 days.
Primary
* Determine whether a 6-week drug trial of modafinil, compared to placebo, is associated with improvement in neurocognitive function as defined by direct assessment of attention in children with cognitive impairment after treatment for a primary brain tumor.
Secondary
* Determine whether modafinil, compared to placebo, is associated with improved executive function, as assessed using the BRIEF executive function and hippocampal learning and executive function tasks from the CogState battery. Determine whether modafinil, compared to placebo, is associated with improved attention, as assessed by the Conners' (3rd Edition) 3 Parent Rating Scale (CPRS-3) - Short Form.
* Determine whether modafinil, compared to placebo, is associated with reduced fatigue as assessed using the PedsQL Multidimensional Fatigue Scale.
* Evaluate the safety of modafinil in this population.
OUTLINE: This is a multicenter study. Participants are randomized to 1 of 2 treatment arms.
* Arm I: Participants receive modafinil orally (PO) once daily (QD) on days 1-42.
* Arm II: Participants receive placebo PO QD on days 1-42. Participants complete a semi-automated, computerized cognitive-testing system (CogState) designed to assess psychomotor, attention/vigilance, memory, and other components of executive function by presenting different tasks, each with its own set of rules, at baseline and after completion of study therapy. Participants also complete the PedsQL Multidimensional Fatigue Scale (Peds QL-MFS).
Parents or legal guardians complete the PedsQL-MFS, the Conners Parent Reported Scale (CPR-3), and the Behavior Rating Inventory of Executive Function (BRIEF) at baseline and after completion of study therapy.
Clinical and/or research staff administer the Systematic Assessment for Treatment Emergency Events (SAFTEE), a semi-structured interview designed to elicit adverse events, at baseline and periodically during study.
After completion of study therapy, participants are followed up for 30 days.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Brain and Central Nervous System Tumors
Cognitive/Functional Effects
Fatigue
Neurotoxicity
Psychosocial Effects of Cancer and Its Treatment
Eligibility Criteria
INCLUSION CRITERIA:
* Age ≥ 6 years and ≤ 18 years 10 months at the time of study entry (so that participants will be \< 19 at the 6 week evaluation, which is the upper age limit for which the included instruments are valid).
* Diagnosis of a primary brain tumor treated with at least one of the following:
1. neurosurgical resection of the brain tumor;
2. cranial irradiation; or
3. any chemotherapy to treat the brain tumor.
* Off-treatment and progression-free for at least 12 months and ≤ 14 years. Treatment cessation is defined as the final dose of chemotherapy, the last dose (fraction) of radiation or date of surgery, whichever occurred last.
* Parent/Legal Guardian and child able to read English or Spanish.
* Vision and hearing (eyeglasses and/or hearing aid permissible) sufficient for valid test administration and cooperation with examinations.
* Availability of a reliable parent or legal guardian who is willing and able to complete all of the outcome measures and fulfill the requirements of the study, including administration of medications and accompanying the participant to all study visits.
* Females of childbearing potential must have a negative pregnancy test result and must agree to use a medically acceptable method of contraception throughout the entire study period and for 30 days after the last dose of study drug.
* Childbearing potential is defined as girls who are \>Tanner stage 2, except for those who have documented pan pituitary insufficiency or other hormonal state incompatible with pregnancy.
* Urine pregnancy tests are acceptable.
EXCLUSION CRITERIA:
* Off treatment \> 14 years
* Inability to perform the testing procedure (for example, because of aphasia, motor deficits affecting the dominant hand, or IQ \< 70)
* Known cardiac disorders including arrhythmias, hypertension requiring treatment or structural heart disease
* Diagnosis of narcolepsy, sick sinus syndrome, arrhythmia or prolonged QTc
* History of stroke or head injury associated with loss of consciousness within 12 months of registration
* History of grade 2 depression or anxiety or treatment with antidepressants, antipsychotics or MAO inhibitors within 30 days of registration
* Concurrent treatment with any medications or substances that are potent inhibitors or inducers of CYP3A4, hepatic enzyme inducing antiepileptic drugs (EIAEDs),or other drugs known to affect the metabolism of modafinil. Examples include but are not limited to itraconazole, ketoconazole, doxycycline, rifampin, St. John's wort, phenytoin, phenobarbital, diazepam, tricyclic antidepressants.
* If patients were previously taking, EIAEDs, they must be off for \> 2 weeks prior to study enrollment.
* Treatment with other stimulant medications within 14 days of registration; however, a diagnosis of ADHD does NOT exclude a child from participation
* Participants with known hypersensitivity to modafinil, armodafinil or any of its components
* Age ≥ 6 years and ≤ 18 years 10 months at the time of study entry (so that participants will be \< 19 at the 6 week evaluation, which is the upper age limit for which the included instruments are valid).
* Diagnosis of a primary brain tumor treated with at least one of the following:
1. neurosurgical resection of the brain tumor;
2. cranial irradiation; or
3. any chemotherapy to treat the brain tumor.
* Off-treatment and progression-free for at least 12 months and ≤ 14 years. Treatment cessation is defined as the final dose of chemotherapy, the last dose (fraction) of radiation or date of surgery, whichever occurred last.
* Parent/Legal Guardian and child able to read English or Spanish.
* Vision and hearing (eyeglasses and/or hearing aid permissible) sufficient for valid test administration and cooperation with examinations.
* Availability of a reliable parent or legal guardian who is willing and able to complete all of the outcome measures and fulfill the requirements of the study, including administration of medications and accompanying the participant to all study visits.
* Females of childbearing potential must have a negative pregnancy test result and must agree to use a medically acceptable method of contraception throughout the entire study period and for 30 days after the last dose of study drug.
* Childbearing potential is defined as girls who are \>Tanner stage 2, except for those who have documented pan pituitary insufficiency or other hormonal state incompatible with pregnancy.
* Urine pregnancy tests are acceptable.
EXCLUSION CRITERIA:
* Off treatment \> 14 years
* Inability to perform the testing procedure (for example, because of aphasia, motor deficits affecting the dominant hand, or IQ \< 70)
* Known cardiac disorders including arrhythmias, hypertension requiring treatment or structural heart disease
* Diagnosis of narcolepsy, sick sinus syndrome, arrhythmia or prolonged QTc
* History of stroke or head injury associated with loss of consciousness within 12 months of registration
* History of grade 2 depression or anxiety or treatment with antidepressants, antipsychotics or MAO inhibitors within 30 days of registration
* Concurrent treatment with any medications or substances that are potent inhibitors or inducers of CYP3A4, hepatic enzyme inducing antiepileptic drugs (EIAEDs),or other drugs known to affect the metabolism of modafinil. Examples include but are not limited to itraconazole, ketoconazole, doxycycline, rifampin, St. John's wort, phenytoin, phenobarbital, diazepam, tricyclic antidepressants.
* If patients were previously taking, EIAEDs, they must be off for \> 2 weeks prior to study enrollment.
* Treatment with other stimulant medications within 14 days of registration; however, a diagnosis of ADHD does NOT exclude a child from participation
* Participants with known hypersensitivity to modafinil, armodafinil or any of its components
Inclusion Criteria
INCLUSION CRITERIA:
* Age ≥ 6 years and ≤ 18 years 10 months at the time of study entry (so that participants will be \< 19 at the 6 week evaluation, which is the upper age limit for which the included instruments are valid).
* Diagnosis of a primary brain tumor treated with at least one of the following:
1. neurosurgical resection of the brain tumor;
2. cranial irradiation; or
3. any chemotherapy to treat the brain tumor.
* Off-treatment and progression-free for at least 12 months and ≤ 14 years. Treatment cessation is defined as the final dose of chemotherapy, the last dose (fraction) of radiation or date of surgery, whichever occurred last.
* Parent/Legal Guardian and child able to read English or Spanish.
* Vision and hearing (eyeglasses and/or hearing aid permissible) sufficient for valid test administration and cooperation with examinations.
* Availability of a reliable parent or legal guardian who is willing and able to complete all of the outcome measures and fulfill the requirements of the study, including administration of medications and accompanying the participant to all study visits.
* Females of childbearing potential must have a negative pregnancy test result and must agree to use a medically acceptable method of contraception throughout the entire study period and for 30 days after the last dose of study drug.
* Childbearing potential is defined as girls who are \>Tanner stage 2, except for those who have documented pan pituitary insufficiency or other hormonal state incompatible with pregnancy.
* Urine pregnancy tests are acceptable.
* Age ≥ 6 years and ≤ 18 years 10 months at the time of study entry (so that participants will be \< 19 at the 6 week evaluation, which is the upper age limit for which the included instruments are valid).
* Diagnosis of a primary brain tumor treated with at least one of the following:
1. neurosurgical resection of the brain tumor;
2. cranial irradiation; or
3. any chemotherapy to treat the brain tumor.
* Off-treatment and progression-free for at least 12 months and ≤ 14 years. Treatment cessation is defined as the final dose of chemotherapy, the last dose (fraction) of radiation or date of surgery, whichever occurred last.
* Parent/Legal Guardian and child able to read English or Spanish.
* Vision and hearing (eyeglasses and/or hearing aid permissible) sufficient for valid test administration and cooperation with examinations.
* Availability of a reliable parent or legal guardian who is willing and able to complete all of the outcome measures and fulfill the requirements of the study, including administration of medications and accompanying the participant to all study visits.
* Females of childbearing potential must have a negative pregnancy test result and must agree to use a medically acceptable method of contraception throughout the entire study period and for 30 days after the last dose of study drug.
* Childbearing potential is defined as girls who are \>Tanner stage 2, except for those who have documented pan pituitary insufficiency or other hormonal state incompatible with pregnancy.
* Urine pregnancy tests are acceptable.
Gender
All
Gender Based
false
Keywords
childhood brain tumor
neurotoxicity
fatigue
cognitive/functional effects
psychosocial effects of cancer and its treatment
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
19 Years
Minimum Age
6 Years
NCT Id
NCT01381718
Org Class
Other
Org Full Name
University of South Florida
Org Study Id
SCUSF 0901
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase II Placebo-Controlled Trial of Modafinil to Improve Neurocognitive Deficits in Children Treated for a Primary Brain Tumor
Primary Outcomes
Outcome Description
CogState Battery. CogState is a semi-automated, computerized cognitive testing system that was developed as a rapid and accurate test of cognitive function specifically for repeated assessment that is sensitive to the effects of medication in children over the age of 5 years and in adults from different language, cultural and socio-economic backgrounds. The CogState tasks to assess processing speed, visual attention, working memory and executive function were used. The CogState battery was administered in the following order: Detection Task, Identification Task, One Card Learning Task, One Back Task, and lastly, the Modified Groton Maze Learning Task. It was administered at baseline and 6 weeks. A positive change from baseline is an improvement. There is not a minimum or maximum since the value is reported as a z-score, but with the mean = 0 and the SD = 1, the range should be between -3 and 3.
Outcome Measure
Change in Age-Adjusted Scores at Week Six From Baseline in the Attention Task of the CogState Battery
Outcome Time Frame
Baseline and 6 weeks
Secondary Ids
Secondary Id
SCUSF-0901
Secondary Id
ACCL0922
Secondary Id
5U10CA081920-11
Secondary Outcomes
Outcome Description
AEs gathered using SAFTEE (Systematic Assessment for Treatment Emergent Effects) and participant report on daily log.
Outcome Time Frame
30 days post intervention
Outcome Measure
Number of Reported Adverse Events (AEs)
Outcome Description
Behavior Rating Inventory of Executive Function (BRIEF). The BRIEF is a behavior rating scale designed to assess executive functions in the home and school environments. The measure was selected to provide parent-reported outcomes of problems related to attention, memory and executive function that occur in everyday life. The instrument was utilized to measure the change in working memory, according to the parent's perspective only, from baseline to 6 weeks. Scores are linear transformations of raw scores into T scores (mean = 50, SD = 10); higher scores indicate greater difficulties. The baseline score was subtracted from the 6 week score. Positive change from baseline is an improvement. The total scale ranges from 0 to 172. A T score \>60 on the BRIEF working memory subscale indicates cognitive impairment.
Outcome Time Frame
Baseline and 6 weeks
Outcome Measure
Change in Working Memory Score at 6 Weeks From Baseline as Assessed on BRIEF
Outcome Description
PedsQL is Pediatric Quality of Life Inventory Multi-dimensional Fatigue Scale. This scale is designed as a generic symptom-specific instrument to measure fatigue. Higher scores indicate fewer symptoms of fatigue. It was administered at baseline and 6 weeks. The score is the sum of the answers. The baseline score was subtracted from the 6 week score. A positive change indicates worsening. The scale total score range is from 0-72 for both the parent and patient reported instruments.
Outcome Time Frame
Baseline and 6 weeks
Outcome Measure
Change in PedsQL Score at 6 Weeks From Baseline
Start Date
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Child
Adult
Maximum Age Number (converted to Years and rounded down)
19
Minimum Age Number (converted to Years and rounded down)
6
Investigators
Investigator Type
Principal Investigator
Investigator Name
Peter Cole
Investigator Email
pcole@montefiore.org
Investigator Phone
718-839-7462