An Efficacy and Safety Study of Oral Netupitant and Palonosetron for the Prevention of Nausea and Vomiting

Inclusion Criteria:

- Naïve to cytotoxic chemotherapy. Previous biological or hormonal therapy will be
permitted.

- Scheduled to receive first course of an anthracycline and cyclophosphamide containing
moderately emetogenic chemotherapy (MEC) regimen for the treatment of a solid
malignant tumor: cyclophosphamide I.V. (500 to 1500 mg/m2) and I.V. doxorubicin (more
or equal to 40 mg/m2) or cyclophosphamide I.V. (500 to 1500 mg/m2) and I.V.
epirubicin (more or equal to 60 mg/m2).

- If scheduled to receive chemotherapy agents of minimal to low emetogenic potential
they could be given on any day.

- ECOG Performance Status of 0, 1, or 2.

- Female patients of either non-childbearing potential or child-bearing potential with
a commitment to use contraceptive methods throughout the clinical trial

- Hematologic and metabolic status adequate for receiving a moderately emetogenic
regimen based on laboratory criteria (Total Neutrophils,Platelets, Bilirubin, Liver
enzymes, Serum Creatinine or Creatinine Clearance)

The following inclusion criteria must be checked prior inclusion at each cycle of the
Multiple-Cycle Extension:

- Participation in the study during the next cycle of chemotherapy is considered
appropriate by the investigator Satisfactory study compliance in the preceding cycle
of chemotherapy and related study procedures.

- Scheduled to receive the same chemotherapy regimen as cycle 1

- Adequate hematologic and metabolic status as defined for cycle 1

Exclusion Criteria:

- If female, pregnant or lactating.

- Current use of illicit drugs or current evidence of alcohol abuse.

- Scheduled to receive any highly emetogenic chemotherapy (HEC) from Day 1 to Day 5 or
moderately emetogenic chemotherapy (MEC) from Day 2 to Day 5 following the allowed
MEC regimen.

- Received or is scheduled to receive radiation therapy to the abdomen or the pelvis
within 1 week prior to Day 1 or between Days 1 to 5 in cycle 1.

- Any vomiting, retching, or mild nausea within 24 hours prior to Day 1.

- Symptomatic primary or metastatic CNS malignancy.

- Active peptic ulcer disease, gastrointestinal obstruction, increased intracranial
pressure, hypercalcemia, an active infection or any uncontrolled medical condition
(other than malignancy) that, in the opinion of the investigator, may confound the
results of the study, represent another potential etiology for emesis and nausea
(other than chemotherapy-induced nausea and vomiting, CINV) or pose unwarranted risks
in administering the study drugs to the patient.

- Known hypersensitivity or contraindication to 5-HT3 receptor antagonists or
dexamethasone.

- Previously received an NK1 receptor antagonist

- Participation in a clinical trial involving oral netupitant administered in
combination with palonosetron.

- Any investigational drugs taken within 4 weeks prior to Day 1 of cycle 1, and/or is
scheduled to receive any investigational drug during the study.

- Systemic corticosteroid therapy at any dose within 72 hours prior to Day 1 of cycle
1.

- Scheduled to receive bone marrow transplantation and/or stem cell rescue therapy.

- Any medication with known or potential antiemetic activity within 24 hours prior to
Day 1 of cycle 1

- Scheduled to receive any strong or moderate inhibitor of CYP3A4 or its intake within
1 week prior to Day 1.

- Scheduled to receive any of the following CYP3A4 substrates: terfenadine, cisapride,
astemizole, pimozide.

- Scheduled to receive any CYP3A4 inducer or its intake within 4 weeks prior to Day 1.

- History or predisposition to cardiac conduction abnormalities, except for incomplete
right bundle branch block.

- History of risk factors for Torsade de Point (heart failure, hypokalemia, family
history of Long QT Syndrome).

- Severe cardiovascular diseases, including myocardial infarction within 3 months prior
to Day 1, unstable angina pectoris, significant valvular or pericardial disease,
history of ventricular tachycardia, symptomatic Congestive Heart Failure (CHF) NYHA
class III-IV, and severe uncontrolled arterial hypertension.

- Any illness or condition that, in the opinion of the investigator, may confound the
results of the study or pose unwarranted risks in administering the investigational
product to the patient.

- Concurrent medical condition that would preclude administration of dexamethasone such
as systemic fungal infection or uncontrolled diabetes.

The following exclusion criteria must be checked prior inclusion at each cycle of the
Multiple-Cycle Extension:

- If female, pregnant or lactating

- Active infection or uncontrolled disease except for malignancy.

- Started any of the restricted medications.

- Any vomiting, retching, or mild nausea within 24 hours prior to Day 1.