A Safety Study of Intravenous Pro-Netupitant and Palonosetron Combination for the Prevention of Nausea and Vomiting
Condition: Chemotherapy-Induced Nausea and Vomiting
MeSH terms: Nausea; Vomiting
Intervention: Pro-netupitant/Palonosetron; Netupitant/Palonosetron; Dexamethasone
Intervention MeSH terms: Dexamethasone; 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: 405.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      NEPA-15-18 is a clinical study assessing safety of pro-netupitant and palonosetron, two
      antiemetic drugs, given with oral dexamethasone. The objective of the study is to evaluate if
      pro-netupitant and palonosetron are safe when administered to prevent nausea and vomiting
      after administration of repeated cycles of chemotherapy.
    

Eligibility criteria:

        Inclusion Criteria:

        Cycle 1

          -  Signed written informed consent

          -  Histologically or cytologically confirmed solid tumor malignancy.

          -  Naïve to cytotoxic chemotherapy. Previous biological or hormonal therapy will be
             permitted.

          -  Scheduled to receive at least 4 repeated consecutive cycles of the following highly
             emetogenic reference chemotherapies (HEC), alone or in combination with other
             chemotherapeutic agents on Day 1: cisplatin administered as a single IV dose of ≥ 70
             mg/m2; cyclophosphamide ≥1500 mg/m2; carmustine (BCNU) >250mg/m2; dacarbazine (DTIC);
             mechloretamine (nitrogen mustard)

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2 .

          -  If a patient is female, she shall be of non-childbearing potential or of childbearing
             potential using reliable contraceptive measures and having a negative urine pregnancy
             test.

          -  Hematologic and metabolic status adequate for receiving an highly emetogenic regimen
             based on laboratory criteria (Total Neutrophils,Platelets, Bilirubin, Liver enzymes,
             Serum Creatinine or Creatinine Clearance)

          -  Able to read, understand, follow the study procedure and complete patient diary.

        Cycles 2 to 4:

        The following inclusion criteria must be checked prior to inclusion at each repeated cycle:

          -  Participation in the study during the next cycle of chemotherapy is considered
             appropriate by the Investigator and does not pose unwarranted risk to the patient.

          -  Scheduled to receive the same chemotherapy regimen as Cycle 1 or one of the reference
             chemotherapies as defined in Inclusion criterion 5 for Cycle 1.

          -  If a patient is female, she shall be of non--childbearing potential or of childbearing
             potential using reliable contraceptive measures and having a negative urine pregnancy
             test.

          -  Adequate hematologic and metabolic status according to the Investigator's opinion.

        Exclusion Criteria:

        Cycle 1

          -  Lactating woman.

          -  Active infection or uncontrolled disease except for malignancy that may pose
             unwarranted risks in administering the study drugs to the patient.

          -  Current use of illicit drugs or current evidence of alcohol abuse.

          -  Scheduled to receive moderately or highly emetogenic chemotherapies from Day 2 to Day
             5.

          -  Received or is scheduled to receive radiation therapy to the abdomen or the pelvis
             within 1 week prior to the start of the reference chemotherapy administration on Day 1
             or between Days 1 to 5.

          -  Any vomiting, retching, or nausea (grade ≥ 1 as defined by National Cancer Institute)
             within 24 hours prior to the start of the reference chemotherapy administration on Day
             1.

          -  Symptomatic primary or metastatic CNS malignancy.

          -  Known hypersensitivity or contraindication to 5-HT3 receptor antagonists, to
             dexamethasone or to NK-1 receptor antagonists.

          -  Known contraindication to the IV administration of 50 mL 5% glucose solution.

          -  Previously received an NK-1 receptor antagonist.

          -  Participation in a previous clinical trial involving IV pro-netupitant or oral
             netupitant administered alone or in combination with palonosetron.

          -  Any investigational drugs (other than those given in this study) taken within 4 weeks
             prior to Day 1, and/or is scheduled to receive any investigational drug during the
             present study.

          -  Systemic corticosteroid therapy at any dose within 72 hours prior to the start of
             reference chemotherapy administration on Day 1. Topical and inhaled corticosteroids
             are permitted.

          -  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 within 1 week prior to Day
             1: terfenadine, cisapride, astemizole, pimozide.

          -  Received within 4 weeks prior to Day 1 or scheduled to receive any CYP3A4 inducer.

          -  Any medication with known or potential antiemetic activity within 24 hours prior to
             the start of reference chemotherapy administration on Day 1 of Cycle 1, including but
             not limited to 5-HT3 receptor antagonists and NK-1 receptor antagonists

          -  History or predisposition to cardiac conduction abnormalities, except for incomplete
             right bundle branch block

          -  History of Torsade de Point or known history of risk factors for Torsade de Point
             (heart failure, hypokalemia, family history of Long QT Syndrome).

          -  Severe cardiovascular diseases diagnosed within 3 months prior to Day 1 of first
             cycle, including myocardial infarction, unstable angina pectoris, significant valvular
             or pericardial disease, history of ventricular tachycardia, symptomatic Congestive
             Heart Failure (CHF) New York Heart Association (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.

        Cycles 2 to 4:

        The following exclusion criteria must be checked prior to inclusion in each repeated cycle:

          -  Lactating woman.

          -  Active infection or uncontrolled disease except for malignancy that may pose
             unwarranted risks in administering the study drugs to the patient.

          -  Started any of the restricted medications.

          -  Any vomiting, retching, or nausea (grade ≥ 1 as defined by National Cancer Institute)
             within 24 hours prior to the start of reference chemotherapy administration on Day 1.

          -  Received or is scheduled to receive radiation therapy to the abdomen or the pelvis
             within 1 week prior to the start of the reference chemotherapy administration on Day 1
             or between Days 1 to 5.

          -  Symptomatic primary or metastatic CNS malignancy.