A Safety Study of Oral Netupitant and Palonosetron for the Prevention of Nausea and Vomiting
Condition: Chemotherapy-Induced Nausea and Vomiting
MeSH terms: Nausea; Vomiting
Intervention: Netupitant and Palonosetron; Aprepitant; Palonosetron; Dexamethasone
Intervention MeSH terms: Dexamethasone; Aprepitant; Palonosetron
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 413.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      NETU-10-29 is a clinical study assessing safety of netupitant and palonosetron, two
      antiemetic drugs, both given with oral dexamethasone. The objective of the study is to
      evaluate if netupitant and palonosetron are safe when administered to prevent nausea and
      vomiting after administration of repeated cycles of chemotherapy.
    

Eligibility criteria:

        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.