Antiemetic Therapy With or Without Olanzapine in Preventing Chemotherapy-Induced Nausea and Vomiting in Patients With Cancer Receiving Highly Emetogenic Chemotherapy

Patients with cancer may receive chemotherapy that may cause nausea and vomiting. The
purpose of this study is to determine if the use of olanzapine in combination with
antiemetic therapy can significantly reduce nausea and vomiting in a large number of
patients receiving chemotherapy. Patients are randomized to one of two treatment arms.
Please see the "Arms and Intervention" sections for more detailed information. The primary
objective is to compare the number of patients with no nausea for the acute (0-24 hours
post-chemotherapy), delayed (24-120 hours post-chemotherapy) and overall periods (0-120
hours post-chemotherapy) for patients receiving HEC. The secondary objectives are:

1. To compare the complete response (CR) (no emetic episodes and no use of rescue
medication) in the acute, delayed and overall periods

2. To compare the incidences of potential toxicities ascribed to olanzapine

Protocol treatment is to begin ≤ 14 days of registration. Patients will receive treatment on
Days 1-4. Patients will be permitted to take rescue therapy of the treating investigator's
choice for nausea and/or emesis/retching, based on clinical circumstances. After completing
treatment, patients will be monitored for side effects.

- Diagnosis of malignant disease

- No prior chemotherapy and scheduled to receive HEC (either cisplatin-containing
regimen or anthracycline + cyclophosphamide [AC])

- Cisplatin at a dose of ≥70mg/m^2, with or without other chemotherapy agent(s) OR

- Anthracycline (60 mg/m^2) plus cyclophosphamide(600 mg/m^2)

- Age ≥18 years

- Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1 or 2

- Required Initial Laboratory Values ≤ 120 days prior to registration

- Serum Creatinine ≤2.0 mg/dL

- Serum glutamic oxaloacetic transaminase (SGOT) or Serum glutamic oxaloacetic
transaminase (SGPT) ≤3 x Upper
Limit of Normal (ULN)

- Absolute neutrophil count (ANC) ≥1500/mm^3

- 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 (per clinician discretion)

- No severe cognitive compromise

- No known history of CNS disease (e.g. brain metastases, seizure disorder)

- No treatment with another antipsychotic agent such as risperidone, quetiapine,
clozapine, phenothiazine or butyrophenone ≤30 days prior to registration or planned
during protocol therapy

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

- No concurrent use of amifostine

- No concurrent abdominal radiotherapy

- No concurrent use of quinolone antibiotic therapy

- 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 (e.g. on insulin or an oral hypoglycemic
agent)