Olanzapine With or Without Fosaprepitant Dimeglumine in Preventing Chemotherapy Induced Nausea and Vomiting in Cancer Patients Receiving Highly Emetogenic Chemotherapy

PRIMARY OBJECTIVES:

I. To compare between the two study arms the proportion of patients with no nausea for the
overall (0-120 hours post-chemotherapy), acute (0-24 hours post-chemotherapy), and delayed
periods (24-120 hours post-chemotherapy) for patients receiving highly emetogenic
chemotherapy (HEC).

SECONDARY OBJECTIVES:

I. To compare between the two study arms the complete response (CR) rates (no emetic episodes
and no use of rescue medication) in the acute, delayed, and overall periods.

II. To compare between the two study arms, the incidences of potential toxicities that have
been ascribed to olanzapine.

III. To perform an economic evaluation of olanzapine and fosaprepitant dimeglumine
(fosaprepitant) versus (vs.) olanzapine in patients receiving HEC (noting that all patients
will also receive dexamethasone and a 5HT3 receptor antagonist).

IV. To explore the efficacy of olanzapine in chemotherapy cycles two to four, for patients
who elect to continue on the same antiemetic regimen received in cycle one, in chemotherapy
cycles two to four (continuation phase), by documenting nausea and complete response.

V. To explore the safety of olanzapine in chemotherapy cycles two to four, for patients who
elect to continue on the same antiemetic regimen received in cycle one, in chemotherapy
cycles two to four (continuation phase), by recording any adverse events or drug related
toxicities.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive palonosetron hydrochloride intravenously (IV) over 30 seconds or
ondansetron hydrochloride IV over 2-5 minutes or orally (PO) on day 1, dexamethasone PO on
days 1-4, fosaprepitant dimeglumine IV over 20-30 minutes on day 1, and olanzapine PO on days
1-4. Treatment may repeat every 4 days for up to 3 courses in the absence of disease
progression or unacceptable toxicity.

ARM II: Patients receive palonosetron hydrochloride IV over 30 seconds or ondansetron
hydrochloride IV over 2-5 minutes or PO on day 1, dexamethasone PO on days 1-4, placebo IV
over 20-30 minutes on day 1, and olanzapine PO on days 1-4. Treatment (with no placebo) may
repeat every 4 days for up to 3 courses in the absence of disease progression or unacceptable
toxicity.

After completion of study, patients are followed up periodically.

Inclusion Criteria:

- Diagnosis of malignant disease of any stage; (stage I through stage IV)

- No prior history of chemotherapy for any malignancy

- Scheduled to receive HEC (highly emetogenic chemotherapy) (either cisplatin-containing
regimen or doxorubicin and cyclophosphamide [AC]); cisplatin, given on a single day,
at a dose of >= 70 mg/m^2, with or without other chemotherapy agent(s) OR doxorubicin
(60 mg/m^2) plus cyclophosphamide (600 mg/m^2)

- No nausea or vomiting =< 24 hours prior to registration

- Negative pregnancy test (serum or urine) done =< 7 days prior to registration, for
women of childbearing potential only

* A female of childbearing potential is a sexually mature female who: 1) has not
undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally
postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in
the preceding 12 consecutive months)

- No known diagnosis of dementia; patients with stable treated brain metastases are
eligible to participate

- No known history of central nervous system (CNS) disease (e.g. seizure disorder)

- No treatment with another antipsychotic agent such as risperidone, quetiapine,
clozapine, phenothiazine or butyrophenone =< 30 days prior to registration

- No chronic phenothiazine administration as an antipsychotic agent (patients may
receive prochlorperazine and other phenothiazines as rescue anti-emetic therapy)

- No use of amifostine within 7 days prior to registration

- No radiotherapy within 7 days prior to registration or planned for one week after the
current dose of chemotherapy

- No use of quinolone antibiotic therapy within 7 days prior to registration

- No chronic alcoholism (as determined by the investigator)

- No known hypersensitivity to olanzapine

- No known cardiac arrhythmia, uncontrolled congestive heart failure or acute myocardial
infarction within the previous six months

- No history of uncontrolled diabetes mellitus, i.e., no diabetic ketoacidosis; within 6
months prior to registration; patients are eligible if they have controlled diabetes
on diet, oral agents, and/or insulin

- Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2

- Patients must be able to read and comprehend English

- Serum creatinine =< 2.0 mg/dL =< 120 days prior to registration

- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 3 x upper limit
of normal (ULN) =< 120 days prior to registration