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

Wake Forest University (WFU)

Status and phase: Completed; Phase 2

Conditions: Cognition Disorders; Brain Tumors; Nervous System Tumors; Fatigue

Treatments: Drug: Armodafinil; Other: placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01032200

U10CA081851 (U.S. NIH Grant/Contract)

IRB00012856

REBACCCWFU97509 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 54 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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)

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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54 participants in 2 patient groups, including a placebo group

Arm I - Armodafinil

Experimental group

Description:

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.

Treatment:

Drug: Armodafinil

Arm II - Placebo

Placebo Comparator group

Description:

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.

Treatment:

Other: placebo