Armodafinil in Treating Fatigue Caused By Radiation Therapy in Patients With Primary Brain Tumors

A Feasibility Study of Armodafinil for Brain Radiation-Induced Fatigue

RATIONALE: Armodafinil may help relieve fatigue and improve quality of life in patients with cancer receiving radiation therapy to the brain.

PURPOSE: This clinical trial is studying how well armodafinil works in treating fatigue caused by radiation therapy in patients with primary brain tumors.

Study Overview

• Status: Completed
• Conditions: Fatigue; Cognition Disorders; Brain Tumors; Nervous System Tumors
• Intervention / Treatment: Other: placebo; Drug: Armodafinil

Detailed Description

OBJECTIVES:

Primary

• To estimate study accrual, adherence, retention, and participation of patients with primary brain tumors undergoing partial- or whole-brain radiotherapy who are randomized to receive armodafinil or placebo.
• To estimate the variability of fatigue, quality of life, and neurocognitive function in these patients.

Secondary

• To obtain a preliminary estimate of the effect of armodafinil on fatigue as measured by the fatigue subscale of the FACIT-F and the Brief Fatigue Inventory.
• To estimate the rates of toxicity and adverse events associated with armodafinil.
• To obtain preliminary estimates of the effect of armodafinil on sleepiness as measured by the Epworth Sleep Scale; overall quality of life and brain-specific quality of life as measured by the FACT-G with the brain subscale; and cognitive function as measured by a comprehensive Wake Forest Cognitive Function Battery.

OUTLINE: This is a multicenter study. Patients are stratified according to therapy (radiotherapy alone vs radiotherapy and chemotherapy) and Karnofsky performance status (60-80% vs 90-100%). Patients are randomized to 1 of 2 arms.

• Arm I: Patients receive oral armodafinil once daily beginning no later than the fifth fraction of brain radiotherapy and continuing for 9-11 weeks in the absence of unacceptable toxicity.
• Arm II: Patients receive oral placebo once daily beginning no later than the fifth fraction of brain radiotherapy and continuing for 9-11 weeks in the absence of unacceptable toxicity.

Patients complete questionnaires assessing fatigue, quality of life, and neurocognitive function at baseline and periodically during study.

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157-1096
      • Wake Forest University Comprehensive Cancer Center

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

• Histologically confirmed primary brain tumor, including any of the following:

  • Glioblastoma multiforme
  • Anaplastic astrocytoma
  • Anaplastic oligodendroglioma
  • Anaplastic mixed oligoastrocytoma
  • Low-grade glioma
  • Meningioma
  • Ependymoma
  • Other primary brain tumor histologies

• Planning to undergo external-beam cranial radiotherapy (partial- or whole-brain radiotherapy) meeting all of the following criteria:

  • Total dose ≥ 4,500 cGy
  • Total number of fractions ≥ 25 fractions
  • Dose per fraction ≥ 150 cGy

PATIENT CHARACTERISTICS:

• Karnofsky performance status 60-100%
• Hemoglobin ≥ 10.0 g/dL (erythropoietin or transfusion allowed for symptomatically anemic patients with a hemoglobin < 10 g/dL)
• Creatinine ≤ 2 mg/dL
• Total bilirubin ≤ 2 times upper limit of normal (ULN)
• SGOT and SGPT ≤ 3 times ULN
• Not pregnant or nursing
• Negative pregnancy test

• Sexually active women of childbearing potential must use a reliable method of birth control

  • It is recommended that patients use non-hormonal contraceptives, in addition to or in place of hormonal contraceptives, during and for one month following treatment with armodafinil
• Prior malignancies allowed

Exclusion Criteria:

• No baseline headaches (i.e., headaches occurring in the week before baseline assessment) of grade 4 severity (defined as severe and disabling headaches, requiring analgesics, and interfering with and preventing function or activities of daily living)

• No concurrent uncontrolled illness that may cause fatigue; interfere with drug absorption, distribution, metabolism, or excretion; or limit compliance with study requirements including, but not limited to, any of the following:

  • Ongoing or active infection
  • Chronic renal insufficiency
  • Psychiatric illness (psychosis, psychotic disorder, history of suicide attempt, or actively suicidal)
  • Extreme social situations (e.g., transportation issues that would preclude study compliance)
• Patients with a history of cardiac issues (symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia) should not use armodafinil as it may cause chest pain, palpitations, dyspnea, and transient ischemic T-wave changes on ECG
• No history of allergic reaction attributed to modafinil or armodafinil
• No anticipated or planned excessive consumption of coffee, tea, and/or caffeine-containing beverages averaging > 600 mg of caffeine/day (i.e., approximately 6 cups of coffee/day, 12 cups of hot tea/day, or 12 cans of cola/day)

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior fractionated external-beam cranial radiotherapy
• More than 30 days since prior monoamine oxidate inhibitors or investigational drugs
• More than 2 weeks since prior and no concurrent modafinil (Provigil), donepezil (Aricept), memantine hydrochloride (Namenda), methylphenidate (Ritalin), dextroamphetamine-amphetamine (Adderall), ginkgo biloba, or any other cognitive function-enhancing drugs
• At least 4 weeks since prior and no concurrent interstitial or intracavitary chemotherapy and/or radiotherapy or stereotactic radiosurgery (i.e., Gamma Knife, Linac, or Cyberknife)
• No concurrent erythropoietin, transfusion, or iron therapy (unless patient is symptomatically anemic with hemoglobin < 10 g/dL)
• Concurrent chemotherapy allowed

• Concurrent hormonal therapy for other malignancies allowed

  • No concurrent non-hormonal therapy (e.g., Herceptin and other targeted agents), or cytotoxic chemotherapy
• No concurrent clopidogrel bisulfate (Plavix)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Arm I - Armodafinil; Patients receive oral armodafinil once daily beginning no later than the fifth fraction of brain radiotherapy and continuing for 9-11 weeks in the absence of unacceptable toxicity.	Drug: Armodafinil; Given orally
PLACEBO_COMPARATOR: Arm II - Placebo; Patients receive oral placebo once daily beginning no later than the fifth fraction of brain radiotherapy and continuing for 9-11 weeks in the absence of unacceptable toxicity.	Other: placebo; Given orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Retention	Retention is defined as the percentage of participants who complete the 4 week post-RT questionnaires.	4 weeks post-RT (approximately 3 months post randomization)
Adherence	Adherence is the percentage of ideal number of pills taken while on study (based on returned diaries)	4 weeks post-RT (approximately 3 months post randomization)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fatigue	Fatigue is measured by the fatigue subscale of the Functional Assessment of Chronic Illness Therapy Questionnaire. It consists of 13 questions each answered on a 0 to 4 scale. The fatigue score is the sum of the responses with some questions reverse scored. The total Score ranges from 0 to 52, with higher scores indicating less fatigue.	4 weeks post-RT
Sleepiness	Sleepiness as measured by the Epworth Sleep Scale. It consists of 8 questions that measure daytime sleepiness in which the patient records their likelihood of dozing or sleeping during a number of routine daily activities. ESS scores range from 0 to 24. Higher scores denote greater sleepiness.	4 weeks post-RT
HVLT-IR	HVLT-IR is the Hopkins Verbal learning test - immediate recall. Participants are given 12 words to remember. They are then asked to recall those words. This is repeated 3 times. Minimum recalled words 0 maximum 36. The HVLT-IR score is the sum of correctly recalled words across the three trials. Higher scores indicate better recall.	4 weeks post-RT

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 1, 2010
• Primary Completion (ACTUAL): January 8, 2013
• Study Completion (ACTUAL): January 8, 2013

Study Registration Dates

• First Submitted: December 13, 2009
• First Submitted That Met QC Criteria: December 13, 2009
• First Posted (ESTIMATE): December 15, 2009

Study Record Updates

• Last Update Posted (ACTUAL): September 28, 2021
• Last Update Submitted That Met QC Criteria: September 7, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: fatigue; adult glioblastoma; adult giant cell glioblastoma; adult gliosarcoma; adult anaplastic astrocytoma; adult anaplastic ependymoma; adult anaplastic meningioma; adult anaplastic oligodendroglioma; adult brain stem glioma; adult diffuse astrocytoma; adult ependymoma; adult myxopapillary ependymoma; adult oligodendroglioma; adult papillary meningioma; adult subependymoma; adult grade I meningioma; adult grade II meningioma; adult grade III meningioma; adult mixed glioma; adult pilocytic astrocytoma; cognitive/functional effects; adult subependymal giant cell astrocytoma; adult pineal gland astrocytoma
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neurocognitive Disorders; Central Nervous System Neoplasms; Neoplasms; Fatigue; Brain Neoplasms; Nervous System Neoplasms; Cognition Disorders; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Central Nervous System Stimulants; Wakefulness-Promoting Agents; Modafinil
• Other Study ID Numbers: IRB00012856; U10CA081851 (U.S. NIH Grant/Contract); REBACCCWFU97509 (OTHER: NCI)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No