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

Official Title: “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.

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.

Intervention(s) in this Clinical Trial

• Drug: armodafinil
  • Given orally
• Other: placebo
  • Given orally

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 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.
• Placebo Comparator: 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.

Primary Measures

• Feasibility (accrual, retention, adherence, patient availability, and agreement to participate in study)
  • Safety Issue?: No

Secondary Measures

• Toxicity as measured by the CTEP active version of the CTCAE
  • Safety Issue?: Yes
• Fatigue as measured by the FACIT-F and Brief Fatigue Inventory
  • Safety Issue?: No
• Overall quality of life as measured by the FACT-Br
  • Safety Issue?: No
• Sleepiness as measured by the Epworth Sleep Scale
  • Safety Issue?: No
• Cognitive function as measured by the Wake Forest Cognitive Function Battery
  • Safety Issue?: No

DISEASE CHARACTERISTICS:

• 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
• Prior malignancies allowed
• 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
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Cardiac arrhythmia
• 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)
• No history of allergic reaction attributed to modafinil or armodafinil
• No anticipated or planned 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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Wake Forest University Other

Overall Clinical Trial Officials and Contacts

Edward G. Shaw, MD Principal Investigator Comprehensive Cancer Center of Wake Forest University  

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT01032200

Study ID Number: CDR0000661335

ClinicalTrials.gov Identifier: NCT01032200

Health Authority: Unspecified

Clinical trial summary from the National Cancer Institute's PDQ® database