Methylphenidate HCl or Modafinil in Treating Young Patients With Excessive Daytime Sleepiness After Cancer Therapy

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.

• methylphenidate hydrochloride (Drug), also known as methylphenidate HCl, Concerta: Given orally
• modafinil (Drug), also known as Provigil: Given orally
• placebo (Drug), also known as potato starch placebo, placebo capsule: Given orally

Primary outcomes

• 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 outcomes

• Adverse Events [29 days]: Adverse events assessed at all subject visits by interviews with the subject and the subject's parent/ primary caregiver.

Sex: All, ages: 8 Years to 18 Years

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).

Participant flow

Outcome results

• Average Daytime Napping Minutes in a Week (Primary), Mean, minutes: Arm I - Methylphenidate Hydrochloride 36.7; Arm II -Modafinil ; Arm III Placebo
• Adverse Events (Secondary), Number, events: Arm I - Methylphenidate Hydrochloride 1; Arm II -Modafinil ; Arm III Placebo

Adverse events

Time frame: 1 month

Other adverse events by term

Limitations and caveats: This study was closed prior to completion due to a lack of feasibility and low accrual by the Data Monitoring and Safety Board (DSMB).

• Gerald Rosen, MD, Study chair, Children's Hospitals and Clinics of Minnesota - St. Paul
• Tom Geller, MD, Study chair, St. Louis University

NIH grants: U10CA081920