A Safety and Efficacy Study of Rolapitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting (CINV) in Subjects Receiving Moderately Emetogenic Chemotherapy (MEC)

• Acute Phase Response [ Time Frame: 0 to 24 hours ] [ Designated as safety issue: No ]
  To determine the effect of rolapitant on complete response rates in the acute (0 to 24 hours) phase of CINV.
• Overall Response Rate [ Time Frame: 0 to 120 hours ] [ Designated as safety issue: No ]
  To determine the effect of rolapitant on complete response rate in the overall (0 to 120 hours) phase of CINV.
• Safety and Tolerability [ Time Frame: 30 days post study drug ] [ Designated as safety issue: No ]
  To evaluate the safety and tolerability of rolapitant in subjects receiving HEC as assessed by the incidence and severity of AEs.

This is a Phase 3, multicenter, randomized, parallel-group, double-blind, active-controlled study of rolapitant in subjects receiving MEC. Rolapitant or placebo will be administered prior to the initiation of chemotherapy on Day 1 with granisetron and dexamethasone. Subjects will record all events of emesis and the 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 the MEC administration through Day 6 in 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 examination, 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.

• Drug: Rolapitant
  200 mg PO
• Drug: Granisetron
  2 mg PO
• Drug: Dexamethasone
  20 mg PO

• Placebo Comparator: Placebo + Granisetron + Dexamethasone
  Day 1: Placebo + Granisetron (2 mg PO)+ Dexamethasone (20 mg PO) Days 2-3: Granisetron (2 mg PO) will be administered orally.
  Interventions:

  • Drug: Granisetron
  • Drug: Dexamethasone
• Experimental: Rolapitant
  Day 1: Rolapitant (200 mg PO) + Granisetron (2 mg PO)+ Dexamethasone (20 mg PO) Days 2-3: Granisetron (2 mg PO) will be administered orally.
  Interventions:

  • Drug: Rolapitant
  • Drug: Granisetron
  • Drug: Dexamethasone

Inclusion Criteria:

• 18 years of age or older, of either gender, and of any race
• Naïve to moderately or highly emetogenic chemotherapy, and is to receive a first course of MEC including one or more of the following agents: cyclophosphamide IV (<1500 mg/m2), doxorubicin, epirubicin, carboplatin, idarubicin, ifosfamide, irinotecan, daunorubicin, cytarabine IV (>1 g/m2).
• Karnofsky performance score of ≥60
• Predicted life expectancy of ≥4 months
• Adequate bone marrow, kidney, and liver function

Exclusion Criteria:

• Contraindication to the administration of prescribed MEC agent,granisetron, or dexamethasone
• Is pregnant or breast feeding
• 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 3 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)
• 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 MECon Day 1 in Cycle 1.