Emend and Ondansetron Compared to Ondansetron Alone to Prevent CINV in Glioma Patients Receiving Temozolomide

Sixty-eight (68) patients will be randomized to each arm of the study. Patient randomization
will be stratified by grade of tumor (1 or 2 versus 3 or 4) and the number of prior
progressions (0 or 1 versus 2). Within each of the 4 strata defined by these factors, a
permuted block randomization scheme will be used to assign patients to receive either
aprepitant in combination with ondansetron or ondansetron alone.

Though the study is comparative, the goal of the study is to determine whether aprepitant is
worthy of further investigation in this setting, and not to make definitive statements about
the comparative effectiveness of ondansetron treatment with or without aprepitant.

Inclusion Criteria:

- Patients must have histologically confirmed diagnosis of glioma (either low or high
grade) and be either chemotherapy naïve or non-naïve and scheduled to receive
temozolomide-based +/- Bevacizumab- based chemotherapy. Patients with recurrent
disease whose diagnostic pathology confirmed glioma (either low or high grade) will
not need re-biopsy.

- Age ≥ 18 years

- ≤ 2 prior chemotherapeutic regimens

- Patient is scheduled to receive temozolomide at either 150 mg/m2 or 200mg/m2 by mouth
for 5 days out of a 28 day cycle +/- bevacizumab.

- Study participation will occur during the first cycle of the 5 day temozolomide
course.

- An interval of at least 6 weeks between prior surgical resection and study enrollment

- Karnofsky ≥ 60%.

- Hematocrit > 29%, absolute neutrophil count (ANC) > 1,000 cells/µl, platelets >
100,000 cells/µl

- Serum creatinine < 1.5 mg/dl, serum glutamic oxaloacetic transaminase (SGOT) and
bilirubin < 1.5 times upper limit of normal

- For patients on oral corticosteroids, they must be stable clinically on
corticosteroids or tapered off prior to starting the study drug. For patients taking
dexamethasone, the dose should not exceed 8 mg qd (or 4 mg twice a day), if clinically
stable, and the dose should not be escalated over entry dose level, if clinically
possible. The patient's dose of dexamethasone will be evaluated by the PI, the
patient's study physician, and/or the study pharmacist on a case by case basis for
safety. All doses of oral corticosteroids will be reduced by 50% to avoid drug to drug
interactions with Aprepitant, unless oral corticosteroids are at physiologic dose
(e.g. dexamethasone 1 mg, prednisone 10 mg, or cortisone 30 mg). It is recommended
that oral corticosteroid doses be escalated back to full dose on Day 7 (2 days after
Aprepitant is discontinued) based on Aprepitant half-life pharmacokinetic data, and
expert clinical opinion.

- Signed informed consent approved by the Institutional Review Board prior to patient
entry

- If sexually active, patients will take contraceptive measures for the duration of
protocol treatment and continue until one month after treatment. The efficacy of
hormonal contraceptives during and for 28 days following the last dose of Aprepitant
may be reduced. Alternative or back-up methods of contraception must be used.

- Approved rescue medication for the treatment of nausea and vomiting is permitted at
the discretion of the investigator. The rescue antiemetics allowed will include:
ondansetron, granisetron and lorazepam.

Exclusion Criteria:

- Pregnant or breast-feeding (While both aprepitant and ondansetron are classified as
Category B drugs, an eligibility criteria for this study is that the patient be
scheduled to receive a temozolomide-based chemotherapy regimen +/- bevacizumab, which
are Category D and C drugs respectively. Therefore, while not considered necessary for
the administration of the current study drugs, a pregnancy test should be a part of
normal clinical care for the patients in this study, if the patient is determined to
be of child-bearing potential.)

- No prior nitrosourea (e.g. lomustine, carmustine)

- Inability or unwillingness to understand or cooperate with study procedures

- Concurrent administration of CYP3A4 enzyme-inducing anti-epileptic drugs (EIAEDs)
including phenytoin, phenobarbitol, carbamazepine, oxcarbazepine or primidone

- Prohibited medications: Patients taking CYP3A4 enzyme inducers and moderate or strong
inhibitors will be excluded from this trial.

- Received any drug with potential anti-emetic effect within 24 hours prior to the start
of study-designated chemotherapeutic agent: HT3 receptor or substance P/neurokinin
1(NK1) receptor antagonists; Dopamine receptor antagonists (metoclopramide);
Phenothiazine anti-emetics (prochlorperazine, thiethylperazine and perphenazine);
Diphenhydramine, scopolamine, chlorpheniramine maleate, trimethobenzamide;
Haloperidol, droperidol, tetrahydrocannabinol, or nabilone

- Any vomiting, retching or NCI Common Toxicity Criteria v.4.0 grade 2-4 nausea 24 hours
preceding chemotherapy

- Ongoing vomiting from any organic etiology

- Will receive radiotherapy of cranium within one week prior to or during the study