Methylphenidate for Cancer-Related Fatigue

NCT01164956 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: 10-146
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 2

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.

Conditions

Cancer

Keywords

methylphenidate; fatigue

Outcome Measures

Primary Outcomes (1)

• 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.

  18 days

Secondary Outcomes (2)

• Rate of Receiving Clinically Definite Answer Regarding the Ability of Experimental Treatment to Reduce Fatigue Using the N-1-T Design

  18 days

• 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).

Study Arms (8)

M-P, P-M, M-P

EXPERIMENTAL

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.

Drug: methylphenidate; Other: Placebo

P-M, P-M, M-P

EXPERIMENTAL

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.

Drug: methylphenidate; Other: Placebo

P-M, M-P, M-P

EXPERIMENTAL

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.

Drug: methylphenidate; Other: Placebo

M-P, M-P, M-P

EXPERIMENTAL

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.

Drug: methylphenidate; Other: Placebo

M-P, P-M, P-M

EXPERIMENTAL

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.

Drug: methylphenidate; Other: Placebo

M-P, M-P, P-M

EXPERIMENTAL

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.

Drug: methylphenidate; Other: Placebo

P-M, P-M, P-M

EXPERIMENTAL

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.

Drug: methylphenidate; Other: Placebo

P-M, M-P, P-M

EXPERIMENTAL

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.

Drug: methylphenidate; Other: Placebo

Interventions

methylphenidate DRUG

Also known as: MPH, Ritalin, Methylin, Concerta

M-P, M-P, M-P; M-P, M-P, P-M; M-P, P-M, M-P; M-P, P-M, P-M; P-M, M-P, M-P; P-M, M-P, P-M; P-M, P-M, M-P; P-M, P-M, P-M

Placebo OTHER

M-P, M-P, M-P; M-P, M-P, P-M; M-P, P-M, M-P; M-P, P-M, P-M; P-M, M-P, M-P; P-M, M-P, P-M; P-M, P-M, M-P; P-M, P-M, P-M

Eligibility Criteria

• Age: 7 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Participants must be receiving cancer-directed treatment at Dana-Farber Cancer Institute/Children's Hospital Boston or have advanced cancer
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Boston Children's Hospital: collaborator

Study Sites (2)

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Neoplasms; Fatigue

Interventions

Methylphenidate; 5,10-dihydro-5-methylphenazine

Condition Hierarchy (Ancestors)

Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

The study was terminated early due to insufficient resources.

Results Point of Contact

• Title: Christina K. Ullrich, MD, MPH
• Organization: Dana-Farber Cancer Institute

Christina_Ullrich@dfci.harvard.edu

617.632.4997

Study Officials

• Christina Ullrich, MD, MPH

  Dana-Farber Cancer Institute/Children's Hospital Boston

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Christina Ullrich, MD, MPH

Model Details: 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.

Study Record Dates

• First Submitted: July 6, 2010
• First Posted: July 19, 2010
• Study Start: July 1, 2011
• Primary Completion: March 1, 2013
• Study Completion: March 1, 2013
• Last Updated: April 26, 2019
• Results First Posted: April 26, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)