Central Nervous System Tumor, Pediatric, Fatigue, Specific Disorders of Sleep
Conditions
Keywords
psychosocial effects of cancer and its treatment, sleep disorders, fatigue, childhood craniopharyngioma
Brief summary
RATIONALE: Methylphenidate hydrochloride or modafinil may help reduce daytime sleepiness and improve the quality of life of patients with excessive daytime sleepiness after cancer therapy. It is not yet known whether methylphenidate hydrochloride or modafinil are more effective than a placebo in reducing daytime sleepiness in these patients. PURPOSE: This randomized phase II trial is studying methylphenidate hydrochloride or modafinil to see how well they work compared with a placebo in treating young patients with excessive daytime sleepiness after cancer therapy.
Detailed description
OBJECTIVES: Primary * Compare the efficacy of methylphenidate hydrochloride and modafinil to placebo in pediatric patients with excessive daytime sleepiness following cancer therapy. Secondary * Compare the efficacy of half dose methylphenidate hydrochloride and modafinil to placebo in these patients. * Assess the effects of these regimens on daytime sleepiness as measured by the Pediatric Daytime Sleepiness Scale or the Cleveland Adolescent Sleepiness Questionnaire. * Assess the effects of somnolence symptoms on fatigue as measured by the PedsQL Multidimensional Fatigue Scale. * Assess the effects of somnolence symptoms on the quality of life as measured by the PedsQL Quality of Life Inventory 4.0. * Determine the incidence of side effects associated with these regimens. * Determine the prevalence of sleep complaints as measured by the Pediatric Sleep Questionnaire. (Exploratory) OUTLINE: This is a multicenter study. Patients are stratified according to age (8-10 years vs 11-12 years vs 13-17 years vs 18-25 years). Patients are randomized to 1 of 3 treatment arms. * Arm I: Patients receive oral methylphenidate hydrochloride extended-release once daily for 7-42 days in the absence of unacceptable toxicity. * Arm II: Patients receive oral modafinil once daily for 7-42 days in the absence of unacceptable toxicity. * Arm III: Patients receive oral placebo once daily for 7-42 days in the absence of unacceptable toxicity. Patients or their parents complete age-specific sleep and quality-of-life questionnaires at baseline and after completion of treatment. Patients or their parents complete daily sleep diaries during the study to collect information about the date, type of day (school, weekend, or vacation), hours of sleep, anytime the actigraph was removed during the day, time the child went to bed, and time the child got out of bed in the morning. Patients are also instructed to wear an actigraph on their non-dominant wrist for 1 week before starting treatment and during the first and last week of treatment (3 weeks total) to assess sleep-wake patterns.
Interventions
DRUGmethylphenidate hydrochloride
Given orally
DRUGmodafinil
Given orally
DRUGplacebo
Given orally
Sponsors
National Cancer Institute (NCI)
University of South Florida
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
8 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
* Patient and family must agree to return to the clinic up to 8 times within 2 months * Children ≥ 8 and \<18 years of age at the time of study entry who were previously treated for: * a hypothalamic tumor * mid-line brain tumor * a tumor involving one or both thalami * craniopharyngioma * diagnosis of hydrocephalus secondary to a brain tumor or treatment of a brain tumor that required placement of a permanent shunt. * Off cancer treatment for at least six months * Proficient in English * Able to swallow capsules * Experiencing symptoms of excessive daytime sleepiness (EDS) for at least three months prior to study entry that is not a result of inadequate sleep hygiene or other known medical disorder. * Negative pregnancy test
Exclusion criteria
* Patients treated with doxorubicin or high dose cyclophosphamide * History of a clinically significant drug sensitivity to methylphenidate, modafinil, armodafinil or any of their components * Known cardiac disorders including arrhythmias, hypertension requiring treatment or structural heart disease * Have taken methylphenidate or modafinil within the last 14 days * Current/concurrent use of antihistamines, benzodiazepine, anticonvulsants or alcohol * Clinical diagnosis of major depression, subclinical depression, or anxiety disorder * History of psychosis or mania * Patients with suicidal ideation * Diagnosis with anemia, untreated hypothyroidism, mononucleosis or narcolepsy * History of substance abuse * Pregnant or breast feeding * A total dietary intake of more than 500 mg of caffeine per day (e.g., approximately ten 330 mL cans of soft drinks, five cups of coffee or tea, or 750 g chocolate per day).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Daytime Napping Minutes in a Week | 29 days | Outcome measure was the total of daytime napping minutes in a week as assessed by participant sleep diaries |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events | 29 days | Adverse events assessed at all subject visits by interviews with the subject and the subject's parent/ primary caregiver. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm I - Methylphenidate Hydrochloride Patients receive oral methylphenidate extended-release once daily for 7-42 days in the absence of unacceptable toxicity. | 1 |
| Arm II -Modafinil Patients receive oral modafinil once daily for 7-42 days in the absence of unacceptable toxicity. | 0 |
| Arm III Placebo Patients receive oral placebo once daily for 7-42 days in the absence of unacceptable toxicity. | 0 |
| Total | 1 |
Baseline characteristics
| Characteristic | Total | Arm I - Methylphenidate Hydrochloride |
|---|---|---|
| Age, Categorical <=18 years | 1 participants | 1 participants |
| Age, Categorical >=65 years | 0 participants | 0 participants |
| Age, Categorical Between 18 and 65 years | 0 participants | 0 participants |
| Age, Continuous | 13.9 years | 13.9 years |
| Gender Female | 0 participants | 0 participants |
| Gender Male | 1 participants | 1 participants |
| Region of Enrollment United States | 1 participants | 1 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 | 1 / 1 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 1 | 0 / 0 | 0 / 0 |
Outcome results
Primary
Average Daytime Napping Minutes in a Week
Outcome measure was the total of daytime napping minutes in a week as assessed by participant sleep diaries
Time frame: 29 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arm I - Methylphenidate Hydrochloride | Average Daytime Napping Minutes in a Week | 36.7 minutes |
Secondary
Adverse Events
Adverse events assessed at all subject visits by interviews with the subject and the subject's parent/ primary caregiver.
Time frame: 29 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I - Methylphenidate Hydrochloride | Adverse Events | 1 events |