A Phase III Randomized, Double-Blind Placebo Controlled Study of Armodafinil (Nuvigil) To Reduce Cancer-Related Fatigue in Patients With Glioblastoma Multiforme

Inclusion Criteria:

- Glioblastoma multiforme who are clinically stable and have completed radiation
therapy > 28 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)

- 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; Note: radiation must be completed, but chemotherapy is allowed

- Negative serum pregnancy test done ≤ 7 days prior to registration, for women of
childbearing potential only, per physician discretion

- 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)
* Note: during the Active Monitoring Phase of a study
(i.e., active treatment and observation), participants must be willing to return to
the consenting institution for follow-up

- Stable dose of corticosteroid ≤ 28 days prior to registration

Exclusion Criteria:

- Any of the following because this study involves an agent whose genotoxic, mutagenic
and teratogenic effects on the developing fetus and newborn are unknown in pregnant
women, nursing women, men or women of childbearing potential who are unwilling to
employ adequate contraception

- History of hypersensitivity to other psychostimulants

- History of steroid psychosis

- History of or currently taking medications for attention deficit hyperactivity
disorder, severe anxiety disorder, schizophrenia, or substance abuse by patient
record and/or self report

- Currently using any other pharmacologic agents or nonpharmacologic interventions to
specifically treat fatigue including psychostimulants, antidepressants, acupuncture,
etc. will be excluded; Note: antidepressants used to treat items other than fatigue
(such as hot flashes or depression) are allowed if the patient has been on a stable
dose for ≥ 30 days and plans to continue for the duration of the trial;

erythropoietin agents to treat anemia are allowed; exercise is allowed

- Anticipating surgery, those with hypothyroidism, profound anemia (hemoglobin level of
< 10 g/dL ≤ 28 days prior to registration), and clinical depression per physician
discretion

- Active or a history of Tourette's syndrome or tic disorder

- History of or active glaucoma

- History of intractable epilepsy, or uncontrolled seizure disorder

- Co-morbid systemic illnesses or other severe concurrent disease which, in the
judgment of the investigator, would make the patient inappropriate for entry into
this study or interfere significantly with the proper assessment of safety and
toxicity of the prescribed regimens

- Receiving any medications or substances that are strong or moderate inhibitors of
cytochrome P450 3A4 (CYP3A4); use of the following strong or moderate inhibitors are
prohibited ≤ 7 days prior to registration:

- Strong Inhibitors of CYP3A4:
 > 5-fold increase in the plasma area under the curve
(AUC) values or more than 80% decrease in clearance
: Indinavir (Crixivan®)

Nelfinavir (Viracept®)
 Atazanavir (Reyataz®)
 Ritonavir (Norvir®)
 Clarithromycin
(Biaxin®, Biaxin XL®)
 Itraconazole (Sporanox®)
 Ketoconazole (Nizoral®)
 Nefazodone
(Serzone®)
 Saquinavir (Fortovase®, Invirase®)
 Telithromycin (Ketek®)


- Moderate Inhibitors of CYP3A4
: > 2-fold increase in the plasma AUC values or 50-80%
decrease in clearance
: Aprepitant (Emend®) Erythromycin (Erythrocin®, E.E.S. ®,
Ery-Tab®, Eryc®, EryPed®, PCE®
 Fluconazole (Diflucan®)
 Grapefruit juice
 Verapamil
(Calan®, Calan SR®, Covera-HS®, Isoptin SR®, Verelan®, Verelan PM®) Diltiazem
(Cardizem®, Cardizem CD®, Cardizem LA®, Cardizem SR®, Cartia XT™) Dilacor XR®, Diltia
XT®, Taztia XT™, Tiazac®)

- Receiving any medications or substances that are inducers of CYP3A4; use of the
following inducers are prohibited ≤ 7 days prior to registration:


- Inducers of CYP3A4: Efavirenz (Sustiva®)
 Nevirapine (Viramune®)
 Carbamazepine
(Carbatrol®, Epitol®, Equetro™, Tegretol®, Tegretol-XR®)
 Modafinil (Provigil®)

Phenobarbital (Luminal®)
 Phenytoin (Dilantin®, Phenytek®)
 Pioglitazone (Actos®)

Rifabutin (Mycobutin®)
 Rifampin (Rifadin®) St. John's Wort