A Phase III, Multicenter, Randomized, Double-blind, Unbalanced (3:1) Active Control Study to Assess the Safety and Describe the Efficacy of Netupitant and Palonosetron for the Prevention of Chemotherapy-induced Nausea and Vomiting in Repeated Chemotherapy Cycles.
- Signed written informed consent.
- Naïve to cytotoxic chemotherapy. Previous biological or hormonal therapy is
- 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,
- 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)
- 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
- 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,
- 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.