Brain Tumors, Cognition Disorders, Fatigue, Nervous System Tumors
Conditions
Keywords
fatigue, cognitive/functional effects, adult giant cell glioblastoma, adult glioblastoma, adult gliosarcoma, adult anaplastic astrocytoma, adult anaplastic oligodendroglioma, adult mixed glioma, adult diffuse astrocytoma, adult pilocytic astrocytoma, adult pineal gland astrocytoma, adult subependymal giant cell astrocytoma, adult oligodendroglioma, adult anaplastic ependymoma, adult ependymoma, adult myxopapillary ependymoma, adult subependymoma, adult anaplastic meningioma, adult grade I meningioma, adult grade II meningioma, adult grade III meningioma, adult papillary meningioma, adult brain stem glioma
Brief summary
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.
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.
Interventions
DRUGArmodafinil
Given orally
OTHERplacebo
Given orally
Sponsors
National Cancer Institute (NCI)
Wake Forest University Health Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Retention | 4 weeks post-RT (approximately 3 months post randomization) | Retention is defined as the percentage of participants who complete the 4 week post-RT questionnaires. |
| Adherence | 4 weeks post-RT (approximately 3 months post randomization) | Adherence is the percentage of ideal number of pills taken while on study (based on returned diaries) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fatigue | 4 weeks post-RT | 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. |
| Sleepiness | 4 weeks post-RT | 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. |
| HVLT-IR | 4 weeks post-RT | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
Armodafinil: Given orally | 26 |
| 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.
placebo: Given orally | 28 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 1 |
| Overall Study | Multiple | 1 | 1 |
| Overall Study | Progression | 1 | 0 |
| Overall Study | Toxicity | 0 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 3 |
Baseline characteristics
| Characteristic | Arm I - Armodafinil | Arm II - Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 7 Participants | 10 Participants | 17 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants | 18 Participants | 37 Participants |
| Age, Continuous | 59 years | 58 years | 59 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants | 28 Participants | 53 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 26 Participants | 25 Participants | 51 Participants |
| Region of Enrollment United States | 26 participants | 28 participants | 54 participants |
| Sex: Female, Male Female | 14 Participants | 15 Participants | 29 Participants |
| Sex: Female, Male Male | 12 Participants | 13 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 26 | 2 / 28 |
| other Total, other adverse events | 26 / 26 | 27 / 27 |
| serious Total, serious adverse events | 10 / 26 | 8 / 27 |
Outcome results
Primary
Adherence
Adherence is the percentage of ideal number of pills taken while on study (based on returned diaries)
Time frame: 4 weeks post-RT (approximately 3 months post randomization)
Population: Participants who returned pill diaries
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arm I - Armodafinil | Adherence | 92.6 percentage of ideal number of pills |
| Arm II - Placebo | Adherence | 95.7 percentage of ideal number of pills |
Primary
Retention
Retention is defined as the percentage of participants who complete the 4 week post-RT questionnaires.
Time frame: 4 weeks post-RT (approximately 3 months post randomization)
Population: All randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I - Armodafinil | Retention | 85 percentage of participants |
| Arm II - Placebo | Retention | 75 percentage of participants |
Secondary
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.
Time frame: 4 weeks post-RT
Population: Participants with any data
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Arm I - Armodafinil | Fatigue | 32.4 units on a scale | Standard Error 2.6 |
| Arm II - Placebo | Fatigue | 36.4 units on a scale | Standard Error 2.5 |
Secondary
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.
Time frame: 4 weeks post-RT
Population: Participants with any data
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Arm I - Armodafinil | HVLT-IR | 21.2 number of correctly recalled words | Standard Error 1.5 |
| Arm II - Placebo | HVLT-IR | 20.0 number of correctly recalled words | Standard Error 1.4 |
Secondary
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.
Time frame: 4 weeks post-RT
Population: Participants with any data
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Arm I - Armodafinil | Sleepiness | 7.2 units on a scale | Standard Error 1 |
| Arm II - Placebo | Sleepiness | 8.3 units on a scale | Standard Error 1 |