Ph3 Safety/Efficacy Study of Rolapitant for the Prevention of CINV in Subjects Receiving Highly Emetogenic Chemotherapy
Condition: Chemotherapy-induced Nausea and Vomiting
MeSH terms: Nausea; Vomiting
Intervention: Rolapitant; Granisetron; dexamethasone; Placebo
Intervention description: (4 X 50 mg capsules) 200 mg PO; 10 mcg/kg IV; 20 mg PO and 8 mg PO; (4 X 0 mg capsules) 0 mg PO
Intervention MeSH terms: Dexamethasone; Granisetron; Rolapitant
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 532.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Rolapitant; Nausea; Vomiting; CINV; Chemotherapy

Summary:

      This is a Phase 3, multicenter, randomized, parallel-group, double-blind, active-controlled
      study of rolapitant in subjects receiving HEC. Rolapitant or placebo will be administered
      prior to initiation of chemotherapy on Day 1 with granisetron and dexamethasone. Subjects
      will record all events of emesis and use of rescue medication for established nausea and/or
      vomiting, and will indicate the severity of nausea they experienced in each of the previous
      24 hours in the Nausea and Vomiting (NV) Subject Diary prior to HEC administration through
      Day 6 of Cycle 1. Health-related quality of life will be measured by the FLIE Questionnaire
      on Day 6 of Cycle 1. Safety and tolerability will be assessed by clinical review of adverse
      events (AEs), physical examinations, electrocardiograms (ECGs), and safety laboratory values.

      All subjects are expected to complete Cycle 1 and will have the option of participating in up
      to five additional cycles.
    

Eligibility criteria:

        Inclusion Criteria:

          -  18 years of age or older, of either gender, and of any race

          -  has never been treated with cisplatin and is to receive the first course of
             cisplatin-based chemotherapy (≥60 mg/m2)

          -  Karnofsky performance score of ≥60

          -  Predicted life expectancy of ≥4 months

          -  Adequate bone marrow, kidney, and liver function

        Exclusion Criteria:

          -  Contraindication to cisplatin, granisetron, or dexamethasone

          -  Is pregnant or breast feeding

          -  Has previously received cisplatin or subject is planning to receive multiple days of
             cisplatin in a single cycle

          -  Has taken the following agents within the last 48 hours 5-HT3
             antagonists,Phenothiazines,Benzamides,Domperidone,Cannabinoids,NK1 antagonist,
             Benzodiazepines

          -  Scheduled to receive any other chemotherapeutic agent with an emetogenicity level of 4
             or above (Hesketh Scale) from Day 2 through Day 6, except on Day 1.

          -  Scheduled to receive any radiation therapy to the abdomen or pelvis from Day -5
             through Day 6

          -  Has received systemic corticosteroids or sedative antihistamines within 72 hours of
             Day 1 of the study except as premedication for chemotherapy (e.g., taxanes,
             pemetrexed)

          -  symptomatic primary or metastatic CNS disease.

          -  Has ongoing vomiting, retching, clinically significant nausea caused by any etiology,
             or has a history of anticipatory nausea and vomiting.

          -  Has vomited and/or has had dry heaves/retching within 24 hours prior to the start of
             cisplatin-based chemotherapy on Day 1 in Cycle 1.