Methylphenidate for Cancer-Related Fatigue
Condition: Cancer
MeSH terms: Fatigue
Intervention: methylphenidate; Placebo
Intervention MeSH terms: Methylphenidate
Phase: Phase 1
Study type: Interventional
Primary purpose: Supportive Care
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: The N-of-1 design randomized participants to 3 potential treatment pairs; Each pair incorporated the 2 drugs under investigation but with different sequence: Methylphenidate then Placebo or Placebo then Methylphenidate. With this design, there are 8 potential permutations/arms.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 3.0
Sex: All
Minimum age: 7 Years
Maximum age: 21 Years
Healthy volunteers: No
Keywords: methylphenidate; fatigue

Summary:

      The overall aim of this pilot study is to conduct a combined N-of-1 trial (N-1-T) of MPH
      (methylphenidate) for amelioration of fatigue in children with cancer, and to evaluate the
      N-1-T design both for individual clinical decision making and for clinical trials in symptom
      management in pediatric oncology patients. Because no one knows which of the study options
      are best, participants will receive liquid MPH on some days and a placebo on other days. We
      will compare how the participant feels on MPH days with how they feel on placebo days to
      determine whether MPH makes a difference.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participants must be receiving cancer-directed treatment at Dana-Farber Cancer
             Institute/Children's Hospital Boston or have advanced cancer

          -  7-21 years old

          -  Laboratory values as outlined in the protocol

          -  Negative pregnancy test (for females of childbearing potential only)

          -  Child and at least one parent/legal guardian has spoken and written knowledge of
             English

          -  Participant has approximately age-appropriate knowledge of English and is able to
             understand and complete the single-item Likert scale for rating fatigue

          -  Baseline pedsFACIT-F score of 20 or greater

          -  Able to reliably take a liquid enterally

          -  Physical examination including measurement of pulse and blood pressure conducted
             within the past 14 days

          -  If the child is on an opioid analgesic, the primary oncologist does not anticipate a
             need to increase opioid during the study

          -  Opioid dose stable for at least 5 days immediately prior to enrollment

          -  No initiation of or change in the dose of benzodiazepine or other sedative/hypnotic
             drug in the week prior to enrollment and no forseeable initiation or change during the
             study

          -  If currently on an SSRI, SNRI, or tricyclic antidepressant, on a stable dose of the
             past week

          -  Participant has telephone access for communication with the study team regarding
             potential dose adjustments and can provide telephone number and alterative phone
             number

        Exclusion Criteria:

          -  Participant is regarded by primary oncologist to be at a high likelihood of death
             within 30 days

          -  Diagnosis of brain tumor, metastatic disease to the brain, or current active CNS
             leukemia

          -  Known history of glaucoma

          -  Receiving palliative sedation

          -  Receipt of MPH or any other psychostimulant, alpha-adrenergic medications,
             neuroleptics, lithium, monoamine oxidase inhibitors, procarbazine or coumadin in the
             14 days prior to enrollment

          -  Significant GI disturbance that would impair absorption of the drug

          -  History of alcohol or substance abuse in the subject. Subjects living with a household
             member with a history of alcohol or substance abuse may be excluded if the
             investigator feels there is a risk of the study medication being abused or diverted

          -  Documented history of psychotic or bipolar disorder, delirium, major depression,
             suicidal ideation, aggressive behavior necessitating psychiatric care, or any other
             psychiatric condition requiring urgent psychiatric evaluation or immediate initiation
             of pharmacotherapy

          -  History of tics or Tourette's syndrome

          -  Prior history of adverse reaction to MPH

          -  Uncontrolled hypertension

          -  Cardiomyopathy, serious structural cardiac abnormalities, or history of any of the
             following: ventricular arrhythmia, myocardial infarction, rheumatic fever, spontaneous
             or unexplained syncope, exercise-induced syncope, or exercise-induced chest pain.

          -  Family history of ventricular arrhythmia, a sudden or unexplained event requiring
             resuscitation or sudden death under age 30 years, known cardiac arrhythmia,
             hypertrophic cardiomyopathy, or dilated cardiomyopathy.

          -  Concurrent participation in a study that prohibits enrollment on any other trials
             involving cancer-directed or symptom-directed therapies, without approval from the
             study PI

          -  Prior or current medical condition that, in the opinion of the PI, could be
             exacerbated by MPH

          -  Pregnant or breastfeeding women

          -  HIV-positive individuals on combination antiretroviral therapy

          -  Treatment of fatigue medications or herbal supplements for fatigue during the 14 days
             prior to enrollment