Nuvigil or Placebo in Newly Diagnosed Malignant Glioma
Condition: Malignant Glioma
MeSH terms: Glioma
Intervention: Nuvigil®; Placebo
Intervention description: Nuvigil® 150 mg/day x 42 days THEN, No More Drug; Placebo x 42 days; THEN, No More Placebo
Intervention MeSH terms: Modafinil
Phase: Phase 2
Study type: Interventional
Primary purpose: Supportive Care
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 6.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: fatigue; external beam radiation; EBRT; radiation therapy; placebo; cognitive function; TMZ; Temozolomide

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.
    

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