Cancer
Conditions
Keywords
methylphenidate, fatigue
Brief 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.
Detailed description
I. To assess the N-1-T as a study design to evaluate a symptom-directed intervention in children with cancer Primary objective -To evaluate the feasibility of conducting an N-1-T to evaluate MPH for cancer-related fatigue in children as a group Secondary objectives * To evaluate the ability of the N-1-T to assess efficacy of MPH for an individual subject statistically and clinically definite answer (regarding the ability of MPH to reduce fatigue) * To explore subject/family and oncologist perspectives on N1T participation * To examine in a preliminary fashion whether there are patient, family, disease or study-related factors that are associated with attrition to help guide future large-scale N1Ts II. To evaluate MPH for treatment of cancer-related fatigue and related symptoms in children Primary objective -To evaluate the effect of MPH on cancer-related fatigue in children based on various assessments including pedsFACIT-F and a unidimensional single-item Likert scale for measuring fatigue Secondary objective -To assess the side effect profile of MPH for fatigue in children with cancer III. To evaluate fatigue assessment tools Primary objective -To evaluate correlation between fatigue scores
Interventions
DRUGmethylphenidate
OTHERPlacebo
Sponsors
Boston Children's Hospital
Dana-Farber Cancer Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
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.
Eligibility
Sex/Gender
ALL
Age
7 Years to 21 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Completion Rate of Two Treatment Pairs Using the N-1-T Design | 18 days | The feasibility of conducting an N-1-T to evaluate MPH for cancer-related fatigue will be determined by the completion rate of two MPH-placebo pairs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Receiving Clinically Definite Answer Regarding the Ability of Experimental Treatment to Reduce Fatigue Using the N-1-T Design | 18 days | Efficacy of the N-1-T design is defined as patient providing a clinically definite answer regarding the ability of MPH to reduce fatigue.Based on the definition of the outcome being evaluated, aggregation of data for all participants is appropriate. |
| Change Over Treatment Pairs in pedsFACIT-F Score | The pedsFACIT-Fwas administered at baseline and at the end of each treatment pair (TP) and related change in score was calculated for each period: baseline to end of TP 1 (day 6); end of TP 1 to end of TP 2 (day 12); end of TP 2 to end of TP 3 (day 18). | The pediatric Functional Assessment of Chronic Illness Therapy-Fatigue (pedsFACIT-F) is an 11-item instrument derived from a comprehensive pediatric item bank that assesses fatigue. (Lai et al. Pediatr Hematol Oncol 2007) Measuring fatigue over the past 7 days in a population of pediatric cancer patients, the pedsFACIT-F instrument has a score ranging from 0-44, with a higher score meaning more fatigue. A minimally important difference (MID) was established as 4.7 points. |
Countries
United States
Participant flow
Recruitment details
3 participants were enrolled between July 2011 and January 2012. Only the arms of these participants are presented.
Participants by arm
| Arm | Count |
|---|---|
| All Participants Participants were randomized to receive 3 treatment pairs of placebo (P) then methylphenidate (M) or M then P. Each M or P was given daily for 3 days and therefore treatment duration was 18 days over 3 treatment pairs. M or P was administered orally at a starting dose of 0.3 mg/kg/dose. For participants \> 40 kg, the maximum of dose in the first treatment pair was 12.5 mg per dose. Dose escalation to maximum 0.5 mg/kg/dose was permitted. | 3 |
| Total | 3 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Side Effects | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Categorical <=18 years | 2 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Age, Continuous | 16 years |
| Region of Enrollment United States | 3 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 3 |
| other Total, other adverse events | 3 / 3 |
| serious Total, serious adverse events | 0 / 3 |
Outcome results
Primary
Completion Rate of Two Treatment Pairs Using the N-1-T Design
The feasibility of conducting an N-1-T to evaluate MPH for cancer-related fatigue will be determined by the completion rate of two MPH-placebo pairs.
Time frame: 18 days
Population: The analysis dataset is comprised of all enrolled patients. Based on the definition of the outcome being evaluated, aggregation of data for all participants is appropriate.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Completion Rate of Two Treatment Pairs Using the N-1-T Design | 1 participants |
Secondary
Change Over Treatment Pairs in pedsFACIT-F Score
The pediatric Functional Assessment of Chronic Illness Therapy-Fatigue (pedsFACIT-F) is an 11-item instrument derived from a comprehensive pediatric item bank that assesses fatigue. (Lai et al. Pediatr Hematol Oncol 2007) Measuring fatigue over the past 7 days in a population of pediatric cancer patients, the pedsFACIT-F instrument has a score ranging from 0-44, with a higher score meaning more fatigue. A minimally important difference (MID) was established as 4.7 points.
Time frame: The pedsFACIT-Fwas administered at baseline and at the end of each treatment pair (TP) and related change in score was calculated for each period: baseline to end of TP 1 (day 6); end of TP 1 to end of TP 2 (day 12); end of TP 2 to end of TP 3 (day 18).
Population: The analysis dataset is comprised of all enrolled patients with data at baseline and end of all treatment pairs.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Participants | Change Over Treatment Pairs in pedsFACIT-F Score | Change from Baseline to end of Treatment Pair 1 | 4 units on a scale |
| All Participants | Change Over Treatment Pairs in pedsFACIT-F Score | Change from end of Treatment Pair 1 to Pair 2 | 2 units on a scale |
| All Participants | Change Over Treatment Pairs in pedsFACIT-F Score | Change from end of Treatment Pair 2 to Pair 3 | 0 units on a scale |
Secondary
Rate of Receiving Clinically Definite Answer Regarding the Ability of Experimental Treatment to Reduce Fatigue Using the N-1-T Design
Efficacy of the N-1-T design is defined as patient providing a clinically definite answer regarding the ability of MPH to reduce fatigue.Based on the definition of the outcome being evaluated, aggregation of data for all participants is appropriate.
Time frame: 18 days
Population: The analysis dataset is comprised of all enrolled patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Rate of Receiving Clinically Definite Answer Regarding the Ability of Experimental Treatment to Reduce Fatigue Using the N-1-T Design | 0 participants |
| P-M, P-M, M-P | Rate of Receiving Clinically Definite Answer Regarding the Ability of Experimental Treatment to Reduce Fatigue Using the N-1-T Design | 1 participants |
| P-M, M-P, M-P | Rate of Receiving Clinically Definite Answer Regarding the Ability of Experimental Treatment to Reduce Fatigue Using the N-1-T Design | 0 participants |