Clinical Trial to Evaluate Short-term Efficacy of Palliative Methylphenidate in Asthenia in Advanced Cancer Patients

Double-blind, Placebo-controlled, Multicenter Randomized Clinical Trial to Evaluate Short-term Efficacy of Palliative Treatment With Methylphenidate in Asthenia in Advanced Cancer Patients

Fatigue is the most prevalent symptom in advanced cancer patients, interfering functional capacity, social relations, wellbeing, and quality of life. Methylphenidate is a central nervous system stimulant that has traditionally been used in cancer patients to manage depression, opioid-induced sedation, hypoactive delirium due to multiorgan failure, and cognitive disorder associated with brain tumors. Although there is evidence from prospective studies of the efficacy of this drug in cancer-related fatigue, the only one randomised clinical trials gave non-conclusive results. In order to define the real efficacy of methylphenidate in this setting, the investigators designed a new clinical trial comparing methylphenidate and placebo in cancer-related fatigue, assessed both by the verbal numeric scale (VNS) included in the Edmonton Symptom Assessment System (ESAS) and the subscale for fatigue of the Functional Assessment of Cancer Therapy (FACT-F). The investigators will include 122 advanced cancer patients with fatigue ≥ 5/10 (VNS, from 0 to 10) and hemoglobin ≥ 9 g/dl. Patients will be randomized to methylphenidate or placebo. Doses will be adapted to response within a range from 10 mg at morning time and 5 at noon, to 25 mg/day. Assessment of response will be performed on day 3 and day 6 with ESAS and FACT-F. Drug-induced adverse events will be checked. The VNS of fatigue on day 6 will be consider the primary endpoint.

Study Overview

• Status: Terminated
• Conditions: Asthenia
• Intervention / Treatment: Drug: methylphenidate; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Clinica Universidad de Navarra

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Advanced cancer; including metastatic, locally advanced or relapsed not amenable for curative treatment.
• Mini.mental status examination results within normal limits.
• Informed consent.
• Estimated life expectancy of at least one month.
• Hemoglobin >= 9 g/dl.
• Asthenia >= 5 (0-10; numeric verbal scale).

Exclusion Criteria:

• History of psychosis.
• Structured suicidal ideation.
• Severe anxiety.
• Severe renal, hepatic or cardiac (arrythmia, hypertension, ischemic heart disease) failure.
• Simultaneous treatment with drugs that may interact with methylphenidate as: coumarinics, anticonvulsivants (phenobarbital, phenitoin, primidone), phenylbutazone, inhibitors of mono-amine-oxidase, guanethidine.
• History of glaucoma.
• Hyperthyroidism.
• History of hypersensibility to methylphenidate.
• Clinical suspicion of: infection, hypercalcemia, hypothyroidism or renal failure.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: methylphenidate; methylphenidate (pill) p.o. 15 to 25 mg daily for six days	Drug: methylphenidate; methylphenidate (pill) p.o. 15 to 25 mg daily for six days
PLACEBO_COMPARATOR: placebo; the same number of pills (p.o.) than methylphenidate for six days	Drug: placebo; placebo (pill) p.o.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intensity of asthenia assessed with the verbal numeric scale (VNS) included on the Edmonton Symptom Assessment System (ESAS)	We are looking for a difference between goups (methylphenidate versus placebo) of 1.5 (numeric rating scale: o to 10)	After six days of therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intensity of asthenia assessed with the subscale for fatigue of the Functional Assessment of Cancer Therapy (FACT-F)		After six days of therapy
Intensity of asthenia assessed with the verbal numeric scale (VNS) included on the Edmonton Symptom Assessment System (ESAS) and the subscale for fatigue of the Functional Assessment of Cancer Therapy (FACT-F).		After three and six days of therapy
Intensity of other symptoms assessed with the Edmonton Symptom Assessment System (ESAS)		After three and six days of treatment
Number of participants with treatment-related adverse events and severity of these adverse events.	We will check for methylphenidate-related adverse events as: restlessness, hyperactivity, hyporexia, nausea and vomiting, dry mouth, palpitations, sleep insomnia, cephalea, muscle cramps, tics, and any other adverse event that could be treatment-related according to investigator. We will include the severity of the adverse event (mild, moderate, or severe), the presumed relationship with treatment, the measured required to treat it, and the final outcome.	After three and six days of treatment
Cognitive level.	We use a specific questionnaire. In order to facilitate its use in fatigued patients it is designed with a limited number of items selected from three validated tools as MMSE, 3MS, and RBANS	After three and six days of treatment

Collaborators and Investigators

• Sponsor: Clinica Universidad de Navarra, Universidad de Navarra
• Investigators: Study Chair: Carlos Centeno Cortes, MD, Phd, Clinica Universidad de Navarra

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (ANTICIPATED): February 1, 2018
• Study Completion (ANTICIPATED): February 1, 2018

Study Registration Dates

• First Submitted: October 8, 2012
• First Submitted That Met QC Criteria: January 18, 2013
• First Posted (ESTIMATE): January 23, 2013

Study Record Updates

• Last Update Posted (ACTUAL): May 9, 2017
• Last Update Submitted That Met QC Criteria: May 8, 2017
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Keywords: randomized controlled trial; advanced cancer; asthenia
• Additional Relevant MeSH Terms: Asthenia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Methylphenidate
• Other Study ID Numbers: METILAS; 2008-002171-27 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED