Netupitant/Palonosetron Hydrochloride and Dexamethasone With or Without Prochlorperazine or Olanzapine in Improving Chemotherapy-Induced Nausea and Vomiting in Patients With Breast Cancer

PRIMARY OBJECTIVES:

I. To determine if control of nausea at cycle 2 in participants who experienced
chemotherapy-induced nausea and vomiting (CINV) at cycle 1 is improved by the addition of
either prochlorperazine or olanzapine to the control arm of netupitant, palonosetron and
dexamethasone.

SECONDARY OBJECTIVES:

I. To determine if olanzapine is more effective than prochlorperazine in controlling nausea
at cycle 2 in participants who experienced CINV at cycle 1 when used in combination with
netupitant, palonosetron and dexamethasone.

II. To determine if control of vomiting at cycle 2 in patients who experienced CINV at cycle
1 is improved by the addition of either prochlorperazine or olanzapine to the control arm of
netupitant, palonosetron and dexamethasone.

III. To determine if olanzapine is more effective than prochlorperazine in controlling
vomiting at cycle 2 in participants who experienced CINV at cycle 1 when used in combination
with netupitant, palonosetron and dexamethasone.

TERTIARY OBJECTIVES:

I. To create an empirically-based algorithm predicting nausea from breast cancer chemotherapy
regimens that takes into account not only state-of-the-art anti-emetic regimens but also
participant factors such as age, race, education, ethnicity, quality of life (QOL), alcohol
consumption, susceptibility to nausea, expectancy, anxiety, level of nausea on the day prior
to treatment, and prior history of nausea.

II. To compare the effects of the interventions on QOL, as assessed by the Functional
Assessment of Cancer Therapy- General (FACT-G), by following the same procedures described
under the primary aim and the first secondary aim, using change in the FACT-G scores as the
response.

III. To provide preliminary data on the frequency and severity of sleep disturbance, fatigue,
anxiety, and dizziness, across treatment conditions.

IV. To provide preliminary data on biological factors (e.g. glutathione [GSH] recycling,
genetic markers) that may help identify a subgroup of patients at high risk for development
of cancer-related or treatment-related side effects, or response to treatment.

OUTLINE:

PART I: Patients receive 1 cycle of standard of care chemotherapy.

PART II: Patients with a nausea score >= 3 at least once on the diary at cycle 1 chemotherapy
are randomized into 1 of 3 groups at cycle 2.

GROUP I: Within 1 hour prior to chemotherapy, patients receive netupitant/palonosetron
hydrochloride orally (PO) on day 1. Within 30 minutes prior to chemotherapy, patients also
receive dexamethasone PO on days 1-4. Patients also receive placebo PO with chemotherapy
every 8 hours (Q8H) on days 1-4.

GROUP II: Patients receive netupitant/palonosetron hydrochloride and dexamethasone as in
Group I. Patients also receive prochlorperazine PO Q8H and placebo PO with chemotherapy on
days 1-4.

GROUP III: Patients receive netupitant/palonosetron hydrochloride and dexamethasone as in
Group I. Patients also receive olanzapine PO and placebo PO Q8H with chemotherapy on days
1-4.

After completion of study treatment, patients are followed up for 30 days.

Inclusion Criteria:

- Have a diagnosis of breast cancer and be chemotherapy naive; NOTE: prior methotrexate
for non-cancerous conditions is allowed

- Be scheduled to receive a single-day chemotherapy regimen that contains doxorubicin
and/or cyclophosphamide and/or carboplatin; Herceptin (trastuzumab) and other
chemotherapy agents will be allowed with any of these regimens

- Be scheduled to receive an antiemetic regimen that does not contain Akynzeo; in
addition, the antiemetic regimen must conform with American Society of Clinical
Oncology (ASCO) Clinical Practice Guidelines at cycle 1

- Be able to read English

- Have the ability to give written informed consent

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

- NOTE: patients 80 years of age or older must have approval from an oncologist or their
designee to participate in this study

- NOTE: patients currently receiving warfarin must have approval from an oncologist or
their designee to participate in this study

- Women of child-bearing potential must agree to use adequate contraception (hormonal or
barrier method of birth control, or abstinence) for the duration of the study and have
a negative pregnancy test within 10 days prior to the initiation of chemotherapy;
should a woman become pregnant or suspect she is pregnant while participating in this
study, she should inform her study physician immediately

- CYCLE II PORTION ONLY: Only participants with a nausea score >= 3 at least once on the
diary assessment from cycle 1 can be randomized for cycle 2

- CYCLE II PORTION ONLY: Participants must be scheduled to receive the same chemotherapy
regimen as received at cycle 1

Exclusion Criteria:

- Have clinical evidence of current or impending bowel obstruction

- Have a known history of central nervous system disease (e.g., brain metastases or a
seizure disorder)

- Have dementia

- Have uncontrolled diabetes mellitus or uncontrolled hyperglycemia

- Have severe hepatic impairment, severe renal impairment, or end-stage renal disease as
determined by the treating physician

- Have had treatment with an antipsychotic agent such as risperidone, quetiapine,
clozapine, a phenothiazine, or a butyrophenone within 30 days before enrollment or
plans for such treatment during the study period; NOTE: participants could have
received prochlorperazine and other phenothiazines as antiemetic therapy on a short
term basis (i.e., =< 5 days)

- Have a known cardiac arrhythmia, uncontrolled congestive heart failure, or acute
myocardial infarction within the previous 6 months

- Be taking benzodiazepines

- Be taking anticholinergic medications

- Be receiving quinolone antibiotic therapy

- Be taking amifostine (Ethiofos)

- Have a known hypersensitivity to olanzapine or to phenothiazines

- CYCLE II PORTION ONLY: Must not have received Akynzeo at cycle 1

- CYCLE II PORTION ONLY: Must still meet all the exclusion criteria for cycle 1