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

Inclusion Criteria:

• Signed written informed consent.

• Naïve to cytotoxic chemotherapy. Previous biological or hormonal therapy is permitted.

• Diagnosed with a malignant tumor.

• If scheduled to receive repeated consecutive courses of chemotherapy, a single dose ofone or more of the following agents administered on Day 1 is allowed:

• Highly emetogenic chemotherapy: any I.V. dose of cisplatin, mechlorethamine,streptozocin, cyclophosphamide more or equal to 1500 mg/m2, carmustine,dacarbazine;

• Moderately emetogenic chemotherapy: any I.V. dose of oxaliplatin, carboplatin,epirubicin, idarubicin, ifosfamide, irinotecan, daunorubicin, doxorubicin,cyclophosphamide I.V. (less than 1500 mg/m2), cytarabine I.V. (more than 1 g/m2),azacidine, alemtuzumab, bendamustine, or clofarabine.

• If scheduled to receive combination regimens, the most emetogenic agent is to be givenas first on Day 1 and the infusion must be completed within 6 hours.

• If scheduled to receive chemotherapy agents of minimal to low emetogenic potential,they are to be given on Day 1 following the most emetogenic agent or on any subsequentstudy day.

• ECOG Performance Status of 0, 1, or 2

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

• Hematologic and metabolic status adequate for receiving a moderately emetogenicregimen based on laboratory criteria (Total Neutrophils,Platelets, Bilirubin, Liverenzymes, Serum Creatinine or Creatinine Clearance)

Exclusion Criteria:

• If female, lactating or pregnant

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

• Scheduled to receive either 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).

• Scheduled to receive moderately or highly emetogenic chemotherapy from Day 2 to Day 5following Day 1 chemotherapy administration.

• Active infection or uncontrolled disease except for malignancy that may poseunwarranted risks in administering the study drugs to the patient.

• Known hypersensitivity or contraindication to 5-HT3 receptor antagonists ordexamethasone.

• Previously received an NK1 receptor antagonist

• Participation in a clinical trial involving oral netupitant administered incombination with palonosetron.

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

• Systemic corticosteroid therapy at any dose within 72 hours prior to Day 1 of cycle 1.Topical and inhaled corticosteroids with a steroid dose of less or equal to 10 mg ofprednisone daily or its equivalent are permitted. Non-study drug dexamethasone aspre-medication in patients scheduled to receive taxanes is allowed.

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

• Scheduled to receive any strong or moderate inhibitor of CYP3A4 or its intake within 1week 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 incompleteright bundle branch block.

• History of risk factors for Torsade de Point (heart failure, hypokalemia, familyhistory of Long QT Syndrome).

• Severe cardiovascular diseases within 3 months prior to Day 1, including myocardialinfarction, unstable angina pectoris, significant valvular or pericardial disease,history of ventricular tachycardia, symptomatic Congestive Heart Failure and severeuncontrolled arterial hypertension.

• Any illness or condition that, in the opinion of the investigator, may confound theresults of the study or pose unwarranted risks in administering the investigationalproduct to the patient.

• Concurrent medical condition that would preclude administration of dexamethasone for 4days such as systemic fungal infection or uncontrolled diabetes.