Phase 3 Safety and Efficacy Study of Rolapitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting (CINV) in Subjects Receiving Highly Emetogenic Chemotherapy (HEC)

• 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 rates 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 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.

• Drug: Rolapitant
  200
• Drug: Granisetron
  10 mcg/kg IV
• Drug: dexamethasone
  20 mg PO and 8 mg PO

• Experimental: Rolapitant
  Day 1: Rolapitant (200 mg PO) + Granisetron (10 mcg/kg IV) + dexamethasone (20 mg PO) Days 2-4: Dexamethasone (8 mg PO) will be administered orally BID.
  Interventions:

  • Drug: Rolapitant
  • Drug: Granisetron
  • Drug: dexamethasone
• Placebo Comparator: Placebo + Granisetron + Dexamethasone
  Day 1: Placebo + Granisetron (10 mcg/kg IV)+ dexamethasone (20 mg PO) Days 2-4: Dexamethasone (8 mg PO) will be administered orally BID.
  Interventions:

  • Drug: Granisetron
  • Drug: dexamethasone

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.