Rolapitant as an Antiemetic in Malignant Glioma Patients Receiving Radiotherapy and Temozolomide

All eligible subjects should receive a planned total dose of 54-60 gray (GY) of radiation and
75 mg/m2 of TMZ daily for a total of six weeks. Patients will be randomized to receive one of
two antiemetic treatment sequences: sequence A that involves administration of ondansetron
alone for 3 weeks followed by a single dose of rolapitant (day 22) plus daily ondansetron for
3 weeks or sequence B that involves a single dose of rolapitant (day 1) plus daily
ondansetron for 3 weeks followed by 3 weeks of daily ondansetron alone. The study has one
primary endpoint: complete response (CR) rate. Participation in this study may result in
reduced chemo-radiation induced nausea and vomiting, however, risks include the common side
effects of rolapitant including decreased appetite, neutropenia, dizziness, dyspepsia,
urinary tract infection, stomatitis, and anemia.

Inclusion Criteria:

- Patients must have histologically-confirmed, newly-diagnosed malignant glioma
(glioblastoma, gliosarcoma, anaplastic astrocytoma, anaplastic oligoastrocytoma,
anaplastic pleomorphic xanthoastrocytoma, or anaplastic oligodendroglioma) and are
scheduled to receive radiotherapy (for a total of 54-60 Gy) and concomitant daily
temozolomide therapy (at a dose of 75 mg/m^2 for one complete 6-week cycle).

- Age ≥ 18 years

- Karnofsky ≥ 60% or ECOG 0-2

- Hematocrit >29%, Absolute Neutrophil Count >1,000 cells/mm^3, platelets >100,000
cells/mm^3

- Serum creatinine <1.4 mg/dl, bilirubin <1.5 times upper limit of normal (ULN)

- Aspartate aminotransferase (AST) ≤ 2.5 x ULN. For subjects with known liver metastases
≤ 5 x ULN, and alanine aminotransferase (ALT) ≤ 2.5 x ULN. For subjects with known
liver metastases ≤ 5 x ULN

- For patients on higher than physiological level of corticosteroids, they must have
been on a stable dose for 1 week prior to initiating study drug, and the dose should
not be escalated over entry dose level, if clinically possible

- Ability and willingness to give informed consent

- Female patients of childbearing potential must have a negative pregnancy test at
Screening

- Female patients of childbearing potential must agree to use an acceptable method of
birth control from the signing of informed consent and to continue its use during the
study and for at least 90 days after the final dose

- Male patients must agree to use an acceptable form of birth control from study Day 1
through at least 90 days after the final dose

Exclusion Criteria:

- Co-medication that may interfere with study results; e.g., immune-suppressive agents
other than corticosteroids

- Co-medications that may interact with rolapitant (e.g. metoprolol/beta blocker,
codeine, pimozide thioridazine) as reviewed by Duke Preston Robert Tisch Brain Tumor
investigator pharmacist.

- Inability or unwillingness to cooperate with the study procedures

- Prophylactic medication for the prevention of nausea and vomiting 24 hours prior to
the start of radiation therapy through the full course of radiation therapy is
prohibited, with the exception of the study drug. Corticosteroids will be allowed for
treatment of cerebral swelling

- Previous participation in any clinical trial involving rolapitant

- Any vomiting, retching, or National Cancer Institute (NCI) Common Toxicity Criteria
version 4.0 grade 2-4 nausea in the 24 hrs. preceding radiation and chemotherapy

- Ongoing vomiting from any organic etiology

- Received rolapitant within 21 days prior to study enrollment

- Prior cancer chemotherapy or radiotherapy

- Any current treatment, medical history, or uncontrolled condition, other than
malignancy, (e.g., alcoholism or signs of alcohol abuse, seizure disorder, medical or
psychiatric condition) that, in the opinion of the investigator, would confound the
results of the study or pose any unwarranted risk in administering study drug to the
subject

- Patient has a known hypersensitivity to the administration of rolapitant or its
excipients

- Patient has a history of severe renal or hepatic impairment, severe bone marrow
suppression, or systemic infection

- Patient is a woman with a positive serum pregnancy test at Screening, is pregnant,
breast-feeding, or is planning to conceive children within the projected duration of
the study treatment

- Patient has taken the following agents within the last 48 hours prior to the start of
treatment with study drug:

- 5-HT3 antagonists (ondansetron, granisetron, dolasetron, tropisetron, etc.).
Palonosetron is not permitted within 7 days prior to administration of investigational
product

- Benzamides (metoclopramide, alizapride, etc.)

- Domperidone

- Cannabinoids

- Natural Killer (NK)-1 antagonist (aprepitant)

- Benzodiazepines (lorazepam, alprazolam, etc.)

- herbal medications or preparations in doses designed to ameliorate nausea or emesis

- Patient has taken phenothiazines (prochlorperazine, fluphenazine, perphenazine,
thiethylperazine, chlorpromazine, etc.) for any indication within the last 48 hours
prior to the start of treatment with study drug

- Patient has ongoing vomiting, retching, dry heaves, or clinically significant nausea
caused by any etiology, or has had such symptoms within 24 hours prior to the start of
Day 1 of the study intervention, or has a history of anticipatory nausea and vomiting

- Patient must not have been dosed with a test drug or blinded study drug in another
investigational study within 30 days or 5 half-lives of the biologic activity of the
test drug, whichever is longer, before the time of first study dose

- Patient who is receiving investigational agent(s) as part of another clinical study at
the time of screening or who anticipates receiving investigational agent(s) during
their scheduled radiotherapy and concomitant daily temozolomide therapy