Nuvigil or Placebo in Newly Diagnosed Malignant Glioma

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine if Nuvigil® improves fatigue experienced by people receiving external beam radiation therapy for the treatment of malignant gliomas. It is also being done to determine if Nuvigil® improves cognitive function (perception, thinking, reasoning, and remembering) and overall quality of life in people receiving external beam radiation therapy for the treatment of malignant gliomas. Another purpose of this study is to see if people who receive Nuvigil® have more or less side effects than people who receive placebo. Placebo is a substance that looks like an active drug but has no active ingredient.

Detailed Description
-----------------
Study visit times will correspond with standard follow-up evaluations for the patient's malignant glioma. Study visits will occur at baseline (Week 0); Week 7, which is when patients stop their use of study drug and their first round of external beam radiation therapy and temozolomide; and at Weeks 10, 18, and 34. The Week 7 evaluation will include: neuropsychological exam, Psychosocial Questionnaires, and questions about the patient's medications and health. The Week 10 and 18 evaluations will include: vital sign measurements, Karnofsky Performance status rating, neurological and neuropsychological exams, psychosocial questionnaires, an Magnetic Resonance Imaging (MRI) of the patient's brain, and questions about their medications and health. The Week 34 evaluation will include: vital sign measurements, Karnofsky Performance status rating, neurological and neuropsychological exams, psychosocial questionnaires, and questions about the patient's medications and health.

Official Title
-----------------
A Randomized, Double Blind, Placebo-Controlled Study Evaluating the Effect of Nuvigil® (Armodafinil) in Newly Diagnosed Malignant Glioma Patients Experiencing Fatigue Secondary to External Beam Radiation Therapy and Concurrent Temozolomide

Conditions
-----------------
Malignant Glioma

Intervention / Treatment
-----------------
* Drug: Nuvigil®
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Ages 18 years or greater at study entry Histologic diagnosis of a supratentorial World Health Organization (WHO) grade 3 anaplastic glioma (including astrocytoma, oligodendroglioma, and mixed oligoastrocytoma) or WHO grade 4 glioblastoma which requires external beam radiation therapy (EBRT) and concurrent temozolomide (TMZ) Have adequate renal and liver function as evidenced by the following screening lab values: Creatinine ≤ 1.7mg/dl; Total Bilirubin ≤ 1.5mg/dl; Transaminases ≤ 4 times above the upper normal limit; Prothrombin time/international normalized ratio (PT/INR) < 1.4 for patients not on warfarin Adequate bone marrow functions as defined by the following lab values: Absolute neutrophil count (ANC) ≥ 1,500/mm³; Platelets ≥ 100,000 cells/mm³; Hemoglobin ≥ 10.0 gm/dL; White blood cell count (WBC) ≥ 3,000/mcL Karnofsky Performance Status ≥ 60% Recovered from the immediate neurosurgical post-operative period (e.g. for craniotomy, at least a 2 week period of time to allow for wound healing) Agrees to use acceptable birth control method(s). Females using steroidal contraception (oral, depot, or implantable) must agree to use an alternative or concomitant method of contraception throughout therapy as well as for one month after discontinuation of therapy. Agrees to avoid alcohol consumption while on therapy Exclusion Criteria: Pre-existing documented traumatic brain injury Pre-existing dementing illness due to degenerative, cerebrovascular, or other static or progressive neurologic process Neurological deficit such as hemineglect or homonymous hemianopsia on baseline neurologic examination that would preclude effective participation in cognitive testing Intracranial space occupying lesion other than malignant glioma or benign asymptomatic meningioma Prior treatment with EBRT or stereotactic radiosurgery (SRS) to the brain Prior treatment with Nuvigil® or Provigil® within 4 weeks prior to study entry Leptomeningeal disease suggested clinically or by radiographic criteria History of left ventricular cardiac hypertrophy Ischemic ECG changes, chest pain, arrhythmia, or other clinically significant manifestations of mitral valve prolapse in association with central nervous system (CNS) stimulant use within the past 6 months Unstable angina or myocardial infarction within the past 6 months Premorbid or ongoing psychosis Currently receiving Ritalin or Tricyclic Antidepressants. Nuvigil has been demonstrated to affect the serum levels of Triazolam and Cyclosporine. Patients taking these medications will be monitored for potential dose adjustments. Other medications that are metabolized by the cytochrome P450 pathway may be potentially affected, but have not been demonstrated to do so in clinical testing. Such medications will be monitored throughout the study for possible dose adjustments. Patients who are experiencing significant fatigue secondary to medical or physiologic causes other than primarily from their malignant gliomas Pregnant, breast-feeding, or lack of willingness to use recommended birth control methods Patients with known hypersensitivity to modafinil, armodafinil, or its inactive ingredients Patients unable to understand or comply with all conditions of the protocol

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A: Nuvigil®<br>Study evaluation times correspond to standard follow-up evaluations for newly diagnosed malignant glioma patients. After 6 weeks of concurrent External Beam Radiation Therapy (EBRT) and Temozolomide (TMZ), there is typically a 4 week treatment break prior to the start of the 6 monthly cycles of TMZ. No further placebo or Nuvigil® will be given after the 6 week treatment regimen. Thus, study evaluations will occur at baseline (Week 0), immediately after completion of EBRT, TMZ, and Nuvigil® or placebo (Week 7), at the end of the 4 week washout period (Week 10), after the first 2 cycles of TMZ (Week 18), and after the 6th cycle of TMZ (Week 34). | Drug: Nuvigil®<br>* Nuvigil® 150 mg/day x 42 days THEN, No More Drug<br>* Other names: Armodafinil;|
| Placebo Comparator: B: Placebo<br>Study evaluation times correspond to standard follow-up evaluations for newly diagnosed malignant glioma patients. After 6 weeks of concurrent EBRT and TMZ, there is typically a 4 week treatment break prior to the start of the 6 monthly cycles of TMZ. No further placebo or Nuvigil® will be given after the 6 week treatment regimen. Thus, study evaluations will occur at baseline (Week 0), immediately after completion of EBRT, TMZ, and Nuvigil® or placebo (Week 7), at the end of the 4 week washout period (Week 10), after the first 2 cycles of TMZ (Week 18), and after the 6th cycle of TMZ (Week 34). | Drug: Placebo<br>* Placebo x 42 days; THEN, No More Placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of Improved Fatigue Experience After Treatment | Determine if Nuvigil® improves fatigue experienced by patients receiving external beam radiation therapy for the treatment of malignant gliomas. Participants who maintained minimal, or experienced improved fatigue experience on a scale of 0 (No fatigue) - 10 (As bad as you can imagine). | 5 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of Improved Cognitive Performance | Determine if Nuvigil® improves cognitive function of patients receiving external beam radiation therapy for the treatment of malignant gliomas. Participants who maintained average (T=50) to slightly below average (T=40 or greater) cognitive function. | 5 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
EBRT, fatigue, external beam radiation, radiation therapy, placebo, cognitive function, TMZ, Temozolomide