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 of one 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 given as 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 subsequent study 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)

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 5 following Day 1 chemotherapy administration.
• Active infection or uncontrolled disease except for malignancy that may 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. Topical and inhaled corticosteroids with a steroid dose of less or equal to 10 mg of prednisone daily or its equivalent are permitted. Non-study drug dexamethasone as pre-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 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 within 3 months prior to Day 1, including myocardial infarction, unstable angina pectoris, significant valvular or pericardial disease, history of ventricular tachycardia, symptomatic Congestive Heart Failure 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 for 4 days such as systemic fungal infection or uncontrolled diabetes.