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

• ClinicalTrials.gov Identifier: NCT01499849
• Recruitment Status: Completed
• First Posted: December 26, 2011
• Results First Posted: November 4, 2015
• Last Update Posted: May 19, 2016
• Sponsor: Tesaro, Inc.
• Information provided by (Responsible Party): Tesaro, Inc.

Study Description

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 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.

Condition or disease	Intervention/treatment	Phase
Chemotherapy-induced Nausea and Vomiting	Drug: Rolapitant; Drug: Granisetron; Drug: dexamethasone; Drug: Placebo	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 532 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: Phase 3, Multicenter, Randomized, Double Blind, Active-Controlled Study of the Safety & Efficacy of Rolapitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting (CINV) in Subjects Receiving Highly Emetogenic Chemotherapy (HEC)
• Study Start Date: February 2012
• Actual Primary Completion Date: May 2014
• Actual Study Completion Date: May 2014

Arms and Interventions

Arm	Intervention/treatment
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.	Drug: Rolapitant; (4 X 50 mg capsules) 200 mg PO; Other Name: Varubi; Drug: Granisetron; 10 mcg/kg IV; Other Names: Kytril; Granisol; Drug: dexamethasone; 20 mg PO and 8 mg PO; Other Name: Decadron
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.	Drug: Granisetron; 10 mcg/kg IV; Other Names: Kytril; Granisol; Drug: dexamethasone; 20 mg PO and 8 mg PO; Other Name: Decadron; Drug: Placebo; (4 X 0 mg capsules) 0 mg PO; Other Name: Placebo to match Rolapitant

Outcome Measures

Primary Outcome Measures :

1. No Emetic Episodes and No Rescue Medication [ Time Frame: >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 emetic episodes and no rescue medication) in the delayed phase (>24 to 120 hours).

Secondary Outcome Measures :

1. Acute Phase Response [ Time Frame: 0 to 24 hours ]
   To determine the effect of rolapitant on complete response rates in the acute (0 to 24 hours)phase of CINV
2. Overall Response Rate [ Time Frame: 0 to 120 hours ]
   To determine the effect of rolapitant on complete response rates in the overall (0 to 120 hours) phase of CINV.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Massachusetts

TESARO Inc

Waltham, Massachusetts, United States, 02451

Sponsors and Collaborators

Tesaro, Inc.

Investigators

• Study Director: Dennis Vargo, MD; Tesaro, Inc.

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Rapoport BL, Chasen MR, Gridelli C, Urban L, Modiano MR, Schnadig ID, Poma A, Arora S, Kansra V, Schwartzberg LS, Navari RM. Safety and efficacy of rolapitant for prevention of chemotherapy-induced nausea and vomiting after administration of cisplatin-based highly emetogenic chemotherapy in patients with cancer: two randomised, active-controlled, double-blind, phase 3 trials. Lancet Oncol. 2015 Sep;16(9):1079-1089. doi: 10.1016/S1470-2045(15)00035-2. Epub 2015 Aug 10.

• Responsible Party: Tesaro, Inc.
• ClinicalTrials.gov Identifier: NCT01499849
• Other Study ID Numbers: TS-P04832
• First Posted: December 26, 2011
• Results First Posted: November 4, 2015
• Last Update Posted: May 19, 2016
• Last Verified: October 2012

Keywords provided by Tesaro, Inc.:

Rolapitant; Nausea; Vomiting; CINV; Chemotherapy

Additional relevant MeSH terms:

Nausea; Vomiting; Signs and Symptoms, Digestive; Dexamethasone; Granisetron; 8-((1-(3,5-bis(trifluoromethyl)phenyl)ethoxy)methyl)-8-phenyl-1,7-diazaspiro(4,5)decan-2-one; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Serotonin Antagonists; Serotonin Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurokinin-1 Receptor Antagonists