Malignant Glioma
Conditions
Keywords
armodafinil, Nuvigil, fatigue
Brief summary
The purpose of this research study is to determine if armodafinil is safe and effective in treating fatigue in patients with malignant gliomas undergoing treatment with radiotherapy plus temodar. Armodafinil is a wakefulness-promoting agent that has been FDA approved for the treatment of excessive daytime sleepiness for a variety of disorders. Armodafinil may also help to reduce radiation-induced fatigue in brain tumor patients.
Detailed description
* Since no one knows for certain if armodafinil improves fatigue in brain tumor patients undergoing radiation therapy, participants will be randomized into one of two study groups. Half of the participants will receive armodafinil and the other half will receive pills with no medicine (placebo). Neither the participant or the study doctor will know what group they are in. * Participants will be given a study medication-dosing calendar and will take either the study drug or placebo orally once a day for 8 weeks. The dose will be adjusted on days 8,22 or 43, depending upon the level of fatigue. Treatment will begin within 10 days from the radiation start date. * Participants will be evaluated via documented clinician telephone call and self-administered questionnaires on days 1, 8, 22, 43 and 57.
Interventions
DRUGArmodafinil
Taken orally once a day in the morning. Dose will change depending upon level of fatigue
OTHERPlacebo
Placebo taken once a day in the morning
Sponsors
Dartmouth-Hitchcock Medical Center
University of California, San Diego
Beth Israel Deaconess Medical Center
Cephalon
Eudocia Quant Lee, MD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 18 years of age or older * Histologically confirmed malignant glioma including anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma (WHO grade III/IV), glioblastoma multiforme (WHO grade IV) or gliosarcoma. Patients with a grade II astrocytoma, mixed oligo-astrocytoma or oligodendroglioma who are being treated with irradiation are also eligible * Scheduled to receive irradiation to a total dose of 50-60 Gy. Patients receiving hyperfractionated radiotherapy are also eligible * KPS of 70% or greater * Electrolytes within normal institutional limits: BUN and Creatinine \< 2.5 x ULN: AST, ALT, Bilirubin \< 2.5 x ULN * Able to swallow medication
Exclusion criteria
* History of recent cardiac arrhythmia or unstable angina * Has taken a psychostimulant or a monoamine oxidase inhibitor on a regular basis within the past 30 days * Clinically significant untreated sleep apnea * A history of clinically significant cardiac disease, including a history of recent myocardial infarction, history of unstable angina, history of left ventricular hypertrophy, or a history of ischemic ECG changes, chest pain, arrhythmia, or other clinically significant manifestations of mitral valve prolapse in association with use of CNS stimulants (e.g. caffeine, amphetamines, methylphenidate) * Uncontrolled hypertension, alcohol or drug abuse, severe headaches, glaucoma, narcolepsy, clinically significant untreated sleep apnea, psychotic disorder or Tourette's syndrome * Patients taking warfarin for anticoagulation are eligible, but monitoring of prothrombin times is suggested as a precaution * Hemoglobin level of less then 11 g/dl * Laboratory evidence of hypothyroidism with an elevated TSH concentration in the blood greater than 5.0 mlU/L * Current treatment or history of psychotic disorder, bipolar disorder, or anxiety disorder * Patients with a score of \> 28 on the Beck depression inventory consistent with severe depression * Known hypersensitivity to armodafinil or related compounds * Patients who have been receiving MAO inhibitors during the past 14 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Fatigue at Day 43 | 43 days | The primary endpoint was the difference in the 42-day change (baseline vs. day 43) in Functional Assessment of Chronic Illness Therapy-Fatigue scale (FACIT-F scale) between the 2 treatment groups (those patients randomized to receive armodafinil and those randomized to the placebo arm). FACIT-F is a well-validated QOL instrument widely used for the assessment of cancer-related fatigue in clinical trials.5 It consists of the 27-item FACT-G (which assesses QOL based on physical, social/family, emotional, and functional well-being) and the 13-item FACIT-F fatigue subscale (which assesses the impact of fatigue on daily activities). Each item is assessed on a 5-point scale (0 = not at all to 4 = very much). By scoring convention, after appropriate reversal scoring of 11 items, the FACIT-F fatigue subscale (FACIT-fatigue) score ranges from 0 to 52 (lower score indicating more fatigue). A score \< 30 indicates severe fatigue. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Quality of Life at Days 22, 43 and 56 | baseline, day 22, day 43, and day 56 | The effects of treatment on overall health-related quality of life quantified with the general Functional Assessment of Cancer Therapy survey (FACT-G) were measured at baseline, at day 22, at the end of radiation (day 43) and 2 weeks after completion of radiation (day 56). The FACT-G assesses quality of life based on physical, social/family, emotional, and functional well-being. Each item is assessed on a 5-point scale (0 = not at all to 4 = very much). The total FACT-G score can range from 0-108, with higher scores indicating a better quality of life. |
| Number of Grade 3-4 Side Effects at Least Possibly Related to Study Treatment | 56 days | To assess the side effect profile of armodafinil in patients with malignant gliomas undergoing radiotherapy with or without standard chemotherapy treatment. |
Countries
United States
Participant flow
Recruitment details
Study activated at Dana-Farber Cancer Institute in August 2008 and was eventually activated at Beth Israel Medical Center , Dartmouth Hitchcock Medical Center, and University of California San Diego. The study closed to new accrual as of April 2014 as the accrual was met.
Pre-assignment details
Randomization was performed by the Quality Assurance for Clinical Trials office at the Dana Farber Cancer Institute. Patients were randomized in a 1:1 basis to each treatment arm with no stratification.
Participants by arm
| Arm | Count |
|---|---|
| Armodafinil Armodafinil: Taken orally once a day in the morning. | 42 |
| Placebo Placebo: Taken orally once a day in the morning. | 39 |
| Total | 81 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Protocol Violation | 2 | 4 |
| Overall Study | Tumor Progression on Study | 0 | 1 |
| Overall Study | Withdrawal by Subject | 7 | 2 |
Baseline characteristics
| Characteristic | Armodafinil | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 56 years | 54 years | 55 years |
| Glioma grade Grade 2 | 1 units on a scale | 4 units on a scale | 5 units on a scale |
| Glioma grade Grade 3 | 14 units on a scale | 12 units on a scale | 26 units on a scale |
| Glioma grade Grade 4 | 25 units on a scale | 22 units on a scale | 47 units on a scale |
| Glioma grade Grade not defined | 2 units on a scale | 1 units on a scale | 3 units on a scale |
| Karnofsky Performance Status (KPS) | 90 Units on a scale | 90 Units on a scale | 90 Units on a scale |
| Sex: Female, Male Female | 18 Participants | 18 Participants | 36 Participants |
| Sex: Female, Male Male | 24 Participants | 21 Participants | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 36 / 42 | 33 / 39 |
| serious Total, serious adverse events | 3 / 42 | 5 / 39 |
Outcome results
Primary
Change From Baseline in Fatigue at Day 43
The primary endpoint was the difference in the 42-day change (baseline vs. day 43) in Functional Assessment of Chronic Illness Therapy-Fatigue scale (FACIT-F scale) between the 2 treatment groups (those patients randomized to receive armodafinil and those randomized to the placebo arm). FACIT-F is a well-validated QOL instrument widely used for the assessment of cancer-related fatigue in clinical trials.5 It consists of the 27-item FACT-G (which assesses QOL based on physical, social/family, emotional, and functional well-being) and the 13-item FACIT-F fatigue subscale (which assesses the impact of fatigue on daily activities). Each item is assessed on a 5-point scale (0 = not at all to 4 = very much). By scoring convention, after appropriate reversal scoring of 11 items, the FACIT-F fatigue subscale (FACIT-fatigue) score ranges from 0 to 52 (lower score indicating more fatigue). A score \< 30 indicates severe fatigue.
Time frame: 43 days
Population: Primary analysis included participants with complete or near complete baseline and day 43 data irrespective of the amount of treatment received.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Armodafinil | Change From Baseline in Fatigue at Day 43 | -1 units on a scale |
| Placebo | Change From Baseline in Fatigue at Day 43 | -3 units on a scale |
p-value: 0.3Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in Quality of Life at Days 22, 43 and 56
The effects of treatment on overall health-related quality of life quantified with the general Functional Assessment of Cancer Therapy survey (FACT-G) were measured at baseline, at day 22, at the end of radiation (day 43) and 2 weeks after completion of radiation (day 56). The FACT-G assesses quality of life based on physical, social/family, emotional, and functional well-being. Each item is assessed on a 5-point scale (0 = not at all to 4 = very much). The total FACT-G score can range from 0-108, with higher scores indicating a better quality of life.
Time frame: baseline, day 22, day 43, and day 56
Population: Analysis included participants with complete or near complete baseline and day 43 data irrespective of the amount of treatment received.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Armodafinil | Change From Baseline in Quality of Life at Days 22, 43 and 56 | FACIT-G (baseline vs day 22) | -1.76 units on a scale |
| Armodafinil | Change From Baseline in Quality of Life at Days 22, 43 and 56 | FACIT-G (baseline vs day 43) | 2.50 units on a scale |
| Armodafinil | Change From Baseline in Quality of Life at Days 22, 43 and 56 | FACIT-G (baseline vs day 56) | 1.83 units on a scale |
| Placebo | Change From Baseline in Quality of Life at Days 22, 43 and 56 | FACIT-G (baseline vs day 22) | -4.94 units on a scale |
| Placebo | Change From Baseline in Quality of Life at Days 22, 43 and 56 | FACIT-G (baseline vs day 43) | -2.30 units on a scale |
| Placebo | Change From Baseline in Quality of Life at Days 22, 43 and 56 | FACIT-G (baseline vs day 56) | -0.84 units on a scale |
Secondary
Number of Grade 3-4 Side Effects at Least Possibly Related to Study Treatment
To assess the side effect profile of armodafinil in patients with malignant gliomas undergoing radiotherapy with or without standard chemotherapy treatment.
Time frame: 56 days
Population: Grade 3 - 4 events at least possibly related to study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Armodafinil | Number of Grade 3-4 Side Effects at Least Possibly Related to Study Treatment | Diarrhea | 1 number of incidents |
| Armodafinil | Number of Grade 3-4 Side Effects at Least Possibly Related to Study Treatment | Hypomagnesemia | 1 number of incidents |
| Armodafinil | Number of Grade 3-4 Side Effects at Least Possibly Related to Study Treatment | Abdominal pain | 1 number of incidents |
| Armodafinil | Number of Grade 3-4 Side Effects at Least Possibly Related to Study Treatment | Ileus | 1 number of incidents |
| Armodafinil | Number of Grade 3-4 Side Effects at Least Possibly Related to Study Treatment | Glaucoma | 0 number of incidents |
| Armodafinil | Number of Grade 3-4 Side Effects at Least Possibly Related to Study Treatment | Mood alteration (agitation) | 0 number of incidents |
| Armodafinil | Number of Grade 3-4 Side Effects at Least Possibly Related to Study Treatment | Dehydration | 1 number of incidents |
| Armodafinil | Number of Grade 3-4 Side Effects at Least Possibly Related to Study Treatment | Obstruction, cecum | 1 number of incidents |
| Armodafinil | Number of Grade 3-4 Side Effects at Least Possibly Related to Study Treatment | Hyperkalemia | 1 number of incidents |
| Armodafinil | Number of Grade 3-4 Side Effects at Least Possibly Related to Study Treatment | Rash | 0 number of incidents |
| Armodafinil | Number of Grade 3-4 Side Effects at Least Possibly Related to Study Treatment | Confusion | 0 number of incidents |
| Armodafinil | Number of Grade 3-4 Side Effects at Least Possibly Related to Study Treatment | Seizure | 1 number of incidents |
| Armodafinil | Number of Grade 3-4 Side Effects at Least Possibly Related to Study Treatment | Hypokalemia | 1 number of incidents |
| Armodafinil | Number of Grade 3-4 Side Effects at Least Possibly Related to Study Treatment | Speech impairment | 0 number of incidents |
| Armodafinil | Number of Grade 3-4 Side Effects at Least Possibly Related to Study Treatment | Insomnia | 1 number of incidents |
| Placebo | Number of Grade 3-4 Side Effects at Least Possibly Related to Study Treatment | Speech impairment | 1 number of incidents |
| Placebo | Number of Grade 3-4 Side Effects at Least Possibly Related to Study Treatment | Insomnia | 0 number of incidents |
| Placebo | Number of Grade 3-4 Side Effects at Least Possibly Related to Study Treatment | Abdominal pain | 0 number of incidents |
| Placebo | Number of Grade 3-4 Side Effects at Least Possibly Related to Study Treatment | Confusion | 1 number of incidents |
| Placebo | Number of Grade 3-4 Side Effects at Least Possibly Related to Study Treatment | Dehydration | 0 number of incidents |
| Placebo | Number of Grade 3-4 Side Effects at Least Possibly Related to Study Treatment | Diarrhea | 1 number of incidents |
| Placebo | Number of Grade 3-4 Side Effects at Least Possibly Related to Study Treatment | Glaucoma | 1 number of incidents |
| Placebo | Number of Grade 3-4 Side Effects at Least Possibly Related to Study Treatment | Hyperkalemia | 0 number of incidents |
| Placebo | Number of Grade 3-4 Side Effects at Least Possibly Related to Study Treatment | Hypokalemia | 0 number of incidents |
| Placebo | Number of Grade 3-4 Side Effects at Least Possibly Related to Study Treatment | Hypomagnesemia | 0 number of incidents |
| Placebo | Number of Grade 3-4 Side Effects at Least Possibly Related to Study Treatment | Ileus | 0 number of incidents |
| Placebo | Number of Grade 3-4 Side Effects at Least Possibly Related to Study Treatment | Mood alteration (agitation) | 1 number of incidents |
| Placebo | Number of Grade 3-4 Side Effects at Least Possibly Related to Study Treatment | Obstruction, cecum | 0 number of incidents |
| Placebo | Number of Grade 3-4 Side Effects at Least Possibly Related to Study Treatment | Rash | 1 number of incidents |
| Placebo | Number of Grade 3-4 Side Effects at Least Possibly Related to Study Treatment | Seizure | 0 number of incidents |