Ph3 Safety/Efficacy Study of Rolapitant for the Prevention of CINV in Subjects Receiving Highly Emetogenic Chemotherapy

Phase 3

Completed

Conditions: Chemotherapy-induced Nausea and Vomiting

Interventions: Drug: Rolapitant
Drug: Granisetron
Drug: Dexamethasone
Drug: Placebo

Registration Number: NCT01500213

Lead Sponsor: Tesaro, Inc.

Brief 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 1-2 hours 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.

Detailed Description: This is a Phase 3, multicenter, randomized, parallel-group, double-blind, active-controlled study of rolapitant in subjects receiving HEC (≥60 mg/m2 of cisplatin-based chemotherapy). Study drug will be administered 1 - 2 hours prior to initiation of chemotherapy on Day 1. Granisetron and dexamethasone will be administered approximately 30 minutes before initiation of chemotherapy on Day 1,except in patients receiving taxanes as part of cisplatin-based chemotherapy. 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 NV Subject Diary prior to HEC administration through Day 6 in Cycle 1. Dexamethasone 8 mg twice daily (part of study regimen) on Days 2 through 4 is NOT considered rescue therapy. 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 AEs, physical examinations including complete neurological assessment, vital signs,electrocardiograms (ECGs), and safety laboratory values including BUN andcreatinine. All subjects are expected to complete Cycle 1 and will have the option of participating in up to five additional cycles. The study will investigate the efficacy of rolapitant for the treatment of CINV during an initial chemotherapy cycle (Cycle 1).

Safety analyses will include data from Cycle 1 and from subsequent cycles. At the Screening Visit, blood samples may be collected and stored in this study and maybe analyzed for future biomarker research related to safety and efficacy. Analysis of these samples may include DNA, RNA, or protein markers. The biomarker blood samples will be stored for up to 2 years post study completion. In addition, PK samples will be collected from subjects enrolled in selected sites.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 555

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
No Emetic Episodes and No Rescue Medication	>24 to 120 hours post chemotherapy	The primary objective of this study is to determine whether administration of rolapitant with granisetron and dexamethasone improves CINV in the delayed phase (\>24 to 120 hours) of CINV compared with administration of placebo with granisetron and dexamethasone in subjects receiving HEC. The primary outcome will be based on complete response (defined as no emesis and no rescue medication) in the delayed phase (\>24 to 120 hours).

Secondary Outcome Measures

Name	Time	Method
Overall Response Rate	0 to 120 hours	To determine the effect of rolapitant on complete response rate in the overall (0 to 120 hours) phase of CINV.
Acute Phase Response	0 to 24 hours	To determine the effect of rolapitant on complete response rates in the acute (0 to 24 hours) phase of CINV.