Armodafinil in Reducing Cancer-Related Fatigue in Patients With High Grade Glioma

Study Overview
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Brief Summary
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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
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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. To evaluate the tolerability at 8 weeks of 150 mg and 250 mg armodafinil in this patient population. To assess the effect of armodafinil at 8 weeks on cognitive function in patients with high grade glioma. To assess the impact of armodafinil on global quality of life and other fatigue endpoints in this patient population with high grade glioma. 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.

Official Title
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A Phase III Randomized, Double-Blind Placebo Controlled Study of Armodafinil (Nuvigil®) To Reduce Cancer-Related Fatigue in Patients With High Grade Glioma

Conditions
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Fatigue

Intervention / Treatment
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* Drug: armodafinil 150 mg
* Other: Placebo
* Drug: armodafinil 250 mg


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients receive 150 mg armodafinil orally every day in the morning for 8 weeks. | Drug: armodafinil 150 mg<br>* given orally<br>|
| Placebo Comparator: Arm II<br>Patients receive placebo orally every day in the morning for 8 weeks. | Other: Placebo<br>* given orally<br>|
| Experimental: Arm III<br>Patients receive 250 mg armodafinil orally every day in the morning for 8 weeks. | Drug: armodafinil 250 mg<br>* given orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | At 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Up to 4 weeks | 
| 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. | Up to 8 weeks | 
| 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. | Up to 8 weeks | 
| 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 | Up to 8 weeks |