Fatigue
Conditions
Brief summary
This randomized phase III trial studies armodafinil to see how well it works in reducing cancer-related fatigue in patients with high grade glioma. Armodafinil may help relieve fatigue in patients with high grade glioma.
Detailed description
Patients experiencing fatigue related to cancer will be asked to take part in this study. Cancer-related fatigue is a very common symptom in patients with cancer. Patients will receive armodafinil or placebo. Please see the Arms section for more details regarding the treatment assignments. The primary objective of this study is to determine preliminary efficacy measured by patient reported fatigue Brief Fatigue Inventory (BFI) at 8 weeks of two doses (150 mg and 250 mg) of armodafinil in treating moderate fatigue compared to placebo in patients with high grade glioma. The secondary objectives of the study are listed below. 1. To evaluate the tolerability at 8 weeks of 150 mg and 250 mg armodafinil in this patient population. 2. To assess the effect of armodafinil at 8 weeks on cognitive function in patients with high grade glioma. 3. To assess the impact of armodafinil on global quality of life and other fatigue endpoints in this patient population with high grade glioma. 4. Explore the correlation between the BFI, Patient-Reported Outcomes Measurement Information System (PROMIS), and Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) measures, as well as, the relationship of fatigue and cognitive difficulties. Patients will receive armodafinil or placebo for a total of 8 weeks.
Interventions
Sponsors
National Cancer Institute (NCI)
Alliance for Clinical Trials in Oncology
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
* Diagnosed with glioblastoma, gliosarcoma, small cell or large cell glioblastoma, glioblastoma with oligo features, glioblastoma with primitive neuroectodermal tumor-like components (GBM-PNET) features, anaplastic astrocytoma, anaplastic oligodendroglioma, or anaplastic oligoastrocytoma who are clinically stable and have completed radiation therapy (excluding stereotactic radiosurgery) \> 21 days and =\< 24 months prior to enrollment; NOTE: clinical stability will be defined as a stable or improved Karnofsky performance status (KPS) compared to the prior month * \>= 6 score on the worst fatigue question of the BFI (Brief Fatigue Inventory, question 3); it is not required for the patient to complete the entire BFI to meet this criterion * Undergone surgery (gross total or subtotal resection) or biopsy and will have been treated with concurrent radiation therapy and chemotherapy as standard of care for glioblastoma, gliosarcoma, small cell or large cell glioblastoma, glioblastoma with oligo features, glioblastoma with primitive neuroectodermal tumor-like components (GBM-PNET) features, anaplastic astrocytoma, anaplastic oligodendroglioma, or anaplastic oligoastrocytoma patients; Note: radiation must be completed, but chemotherapy is allowed; patients who are currently using Optune device will be eligible to participate in this trial * Negative serum pregnancy test done =\< 7 days prior to registration only for women determined to be of childbearing potential by their treating physician * Ability to complete questionnaire(s) by themselves or with assistance * Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, 2 or 3 * Provide informed written consent * Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study) * Stable dose of corticosteroid \>= 14 days prior to registration
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Participants With a Response in Terms of a Clinically Meaningful Improvement in Patient-reported Fatigue at 8 Weeks. | At 8 weeks | A response is defined as an improvement of 2 points on the 0-10 scale of the usual fatigue on the Brief Fatigue Inventory (BFI). The number of participants with a response in terms of a clinically meaningful improvement in patient-reported fatigue at 8 weeks. Scale: 0 (No fatigue) - 10 (As bad as you can imagine) Interpretation: higher scores mean a worse outcome |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fatigue: Brief Fatigue Inventory (BFI): The Number of Participants With a Response in Terms of a Clinically Meaningful Improvement in Patient-reported Fatigue at 4 Weeks. | Up to 4 weeks | A response is defined as an improvement of 2 points on the 0-10 scale of the usual fatigue on the Brief Fatigue Inventory (BFI). The number of participants with a response in terms of a clinically meaningful improvement in patient-reported fatigue at 4 weeks Scale: 0 (No fatigue) - 10 (As bad as you can imagine) Interpretation: higher scores mean a worse outcome |
| Cognitive Function: Assessed by the Change in Z Score for Symbol Digit Modalities Test (SDMT) From Baseline to End of Week 8 | Up to 8 weeks | The participant is presented with a page headed by a key that pairs the single digits 1-9 with nine symbols. Rows below contain only symbols, the subject's task is to orally report the correct number in the spaces below. After completing the first 10 items with guidance, the subject is timed to determine how many responses can be made in 90 seconds. Range score: not applicable. Higher scores mean a better outcome. Explored domain: Sustained attention and information processing speed. Each neuropsychological measure was converted to an age-normative z score using published normative data. Impaired SDMT performance was defined as falling one standard deviation or more below the normative mean. |
| Change in Quality of Life as Measured by Linear Analogue Self Assessment (LASA) From Baseline to End of Weeks 4 and 8 | Up to 8 weeks | Quality of life: Linear Analogue Self Assessment (LASA) will be analyzed comparing the total score for each treatment testing for change from baseline to four and eight weeks. Linear Analogue Self Assessment (LASA) is a 12 global QOL tool to which measures 10 subscales: overall QOL, physical well-being, fatigue, frequency and severity of pain, as well as social functioning and spiritual, emotional and mental well-being. All subscales were converted to a scale of 0-100, with higher scores indicating better QOL. Total score is the average of all 10 subscales. |
| Number of Participants Who Experienced at Least One Grade 3 or Higher Adverse Events Deemed at Least Possibly Related to Treatment Via the CTCAE Version 4.0 | Up to 8 weeks | The number of participants who experienced at least one grade 3 or higher adverse events deemed at least possibly related to treatment via the CTCAE version 4.0 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm I (150 mg Armodafinil) Patients receive 150 mg armodafinil orally every day in the morning for 8 weeks. | 109 |
| Arm II (250 mg Armodafinil) Patients receive 250 mg armodafinil orally every day in the morning for 8 weeks. | 110 |
| Arm III (Placebo) Patients receive placebo orally every day in the morning for 8 weeks. | 109 |
| Total | 328 |
Baseline characteristics
| Characteristic | Arm I (150 mg Armodafinil) | Arm II (250 mg Armodafinil) | Arm III (Placebo) | Total |
|---|---|---|---|---|
| Age, Continuous | 58.3 years STANDARD_DEVIATION 11.92 | 56.9 years STANDARD_DEVIATION 12.21 | 56.6 years STANDARD_DEVIATION 12.8 | 57.3 years STANDARD_DEVIATION 12.3 |
| ECOG Performance Status 0 | 18 Participants | 28 Participants | 23 Participants | 69 Participants |
| ECOG Performance Status 1 | 60 Participants | 58 Participants | 62 Participants | 180 Participants |
| ECOG Performance Status 2 | 23 Participants | 22 Participants | 16 Participants | 61 Participants |
| ECOG Performance Status 3 | 8 Participants | 2 Participants | 8 Participants | 18 Participants |
| Race/Ethnicity, Customized Race Non-White | 8 Participants | 5 Participants | 5 Participants | 18 Participants |
| Race/Ethnicity, Customized Race White | 101 Participants | 105 Participants | 104 Participants | 310 Participants |
| Sex: Female, Male Female | 46 Participants | 46 Participants | 43 Participants | 135 Participants |
| Sex: Female, Male Male | 63 Participants | 64 Participants | 66 Participants | 193 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 109 | 2 / 110 | 1 / 109 |
| other Total, other adverse events | 55 / 109 | 60 / 110 | 42 / 109 |
| serious Total, serious adverse events | 12 / 109 | 9 / 110 | 8 / 109 |
Outcome results
Primary
The Number of Participants With a Response in Terms of a Clinically Meaningful Improvement in Patient-reported Fatigue at 8 Weeks.
A response is defined as an improvement of 2 points on the 0-10 scale of the usual fatigue on the Brief Fatigue Inventory (BFI). The number of participants with a response in terms of a clinically meaningful improvement in patient-reported fatigue at 8 weeks. Scale: 0 (No fatigue) - 10 (As bad as you can imagine) Interpretation: higher scores mean a worse outcome
Time frame: At 8 weeks
Population: Participants who completed the study are included in this analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I (150 mg Armodafinil) | The Number of Participants With a Response in Terms of a Clinically Meaningful Improvement in Patient-reported Fatigue at 8 Weeks. | 29 Participants |
| Arm II (250 mg Armodafinil) | The Number of Participants With a Response in Terms of a Clinically Meaningful Improvement in Patient-reported Fatigue at 8 Weeks. | 27 Participants |
| Arm III (Placebo) | The Number of Participants With a Response in Terms of a Clinically Meaningful Improvement in Patient-reported Fatigue at 8 Weeks. | 29 Participants |
p-value: 0.9601Fisher Exact
Secondary
Change in Quality of Life as Measured by Linear Analogue Self Assessment (LASA) From Baseline to End of Weeks 4 and 8
Quality of life: Linear Analogue Self Assessment (LASA) will be analyzed comparing the total score for each treatment testing for change from baseline to four and eight weeks. Linear Analogue Self Assessment (LASA) is a 12 global QOL tool to which measures 10 subscales: overall QOL, physical well-being, fatigue, frequency and severity of pain, as well as social functioning and spiritual, emotional and mental well-being. All subscales were converted to a scale of 0-100, with higher scores indicating better QOL. Total score is the average of all 10 subscales.
Time frame: Up to 8 weeks
Population: Participants with LASA data available at all specified time points are included in this analysis. The number analyzed in row differ from the Overall number of participants who completed the study due to missing data (i.e. participants did not complete the LASA at either week 4 and/or week 8 time point(s)).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Arm I (150 mg Armodafinil) | Change in Quality of Life as Measured by Linear Analogue Self Assessment (LASA) From Baseline to End of Weeks 4 and 8 | Baseline to Week 4 | 2.0 units on a scale |
| Arm I (150 mg Armodafinil) | Change in Quality of Life as Measured by Linear Analogue Self Assessment (LASA) From Baseline to End of Weeks 4 and 8 | Baseline to Week 8 | 4.0 units on a scale |
| Arm II (250 mg Armodafinil) | Change in Quality of Life as Measured by Linear Analogue Self Assessment (LASA) From Baseline to End of Weeks 4 and 8 | Baseline to Week 4 | 0.5 units on a scale |
| Arm II (250 mg Armodafinil) | Change in Quality of Life as Measured by Linear Analogue Self Assessment (LASA) From Baseline to End of Weeks 4 and 8 | Baseline to Week 8 | 3.0 units on a scale |
| Arm III (Placebo) | Change in Quality of Life as Measured by Linear Analogue Self Assessment (LASA) From Baseline to End of Weeks 4 and 8 | Baseline to Week 4 | 2.0 units on a scale |
| Arm III (Placebo) | Change in Quality of Life as Measured by Linear Analogue Self Assessment (LASA) From Baseline to End of Weeks 4 and 8 | Baseline to Week 8 | 2.0 units on a scale |
Comparison: Baseline to Week 4p-value: 0.9122Kruskal-Wallis
Comparison: Baseline to Week 8p-value: 0.8559Kruskal-Wallis
Secondary
Cognitive Function: Assessed by the Change in Z Score for Symbol Digit Modalities Test (SDMT) From Baseline to End of Week 8
The participant is presented with a page headed by a key that pairs the single digits 1-9 with nine symbols. Rows below contain only symbols, the subject's task is to orally report the correct number in the spaces below. After completing the first 10 items with guidance, the subject is timed to determine how many responses can be made in 90 seconds. Range score: not applicable. Higher scores mean a better outcome. Explored domain: Sustained attention and information processing speed. Each neuropsychological measure was converted to an age-normative z score using published normative data. Impaired SDMT performance was defined as falling one standard deviation or more below the normative mean.
Time frame: Up to 8 weeks
Population: Participants who completed the Symbol Digit Modalities Test at baseline and end of week 8 are included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I (150 mg Armodafinil) | Cognitive Function: Assessed by the Change in Z Score for Symbol Digit Modalities Test (SDMT) From Baseline to End of Week 8 | 0.0 units on a scale |
| Arm II (250 mg Armodafinil) | Cognitive Function: Assessed by the Change in Z Score for Symbol Digit Modalities Test (SDMT) From Baseline to End of Week 8 | 0.3 units on a scale |
| Arm III (Placebo) | Cognitive Function: Assessed by the Change in Z Score for Symbol Digit Modalities Test (SDMT) From Baseline to End of Week 8 | 0.0 units on a scale |
p-value: 0.3272Kruskal-Wallis
Secondary
Fatigue: Brief Fatigue Inventory (BFI): The Number of Participants With a Response in Terms of a Clinically Meaningful Improvement in Patient-reported Fatigue at 4 Weeks.
A response is defined as an improvement of 2 points on the 0-10 scale of the usual fatigue on the Brief Fatigue Inventory (BFI). The number of participants with a response in terms of a clinically meaningful improvement in patient-reported fatigue at 4 weeks Scale: 0 (No fatigue) - 10 (As bad as you can imagine) Interpretation: higher scores mean a worse outcome
Time frame: Up to 4 weeks
Population: Participants who completed the study are included in this analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I (150 mg Armodafinil) | Fatigue: Brief Fatigue Inventory (BFI): The Number of Participants With a Response in Terms of a Clinically Meaningful Improvement in Patient-reported Fatigue at 4 Weeks. | 37 Participants |
| Arm II (250 mg Armodafinil) | Fatigue: Brief Fatigue Inventory (BFI): The Number of Participants With a Response in Terms of a Clinically Meaningful Improvement in Patient-reported Fatigue at 4 Weeks. | 31 Participants |
| Arm III (Placebo) | Fatigue: Brief Fatigue Inventory (BFI): The Number of Participants With a Response in Terms of a Clinically Meaningful Improvement in Patient-reported Fatigue at 4 Weeks. | 30 Participants |
p-value: 0.7877Fisher Exact
Secondary
Number of Participants Who Experienced at Least One Grade 3 or Higher Adverse Events Deemed at Least Possibly Related to Treatment Via the CTCAE Version 4.0
The number of participants who experienced at least one grade 3 or higher adverse events deemed at least possibly related to treatment via the CTCAE version 4.0
Time frame: Up to 8 weeks
Population: Participants who started the study are included in this analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I (150 mg Armodafinil) | Number of Participants Who Experienced at Least One Grade 3 or Higher Adverse Events Deemed at Least Possibly Related to Treatment Via the CTCAE Version 4.0 | 6 Participants |
| Arm II (250 mg Armodafinil) | Number of Participants Who Experienced at Least One Grade 3 or Higher Adverse Events Deemed at Least Possibly Related to Treatment Via the CTCAE Version 4.0 | 8 Participants |
| Arm III (Placebo) | Number of Participants Who Experienced at Least One Grade 3 or Higher Adverse Events Deemed at Least Possibly Related to Treatment Via the CTCAE Version 4.0 | 3 Participants |