Ph 3 Safety/Efficacy Study of Rolapitant for Prevention of CINV in Subjects Receiving Moderately Emetogenic Chemotherapy

Study Description

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Brief Summary:

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.

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 MEC. Rolapitant or placebo will be administered orally 1-2 hours prior to the initiation of chemotherapy on Day 1. Granisetron (2 mg PO) and dexamethasone (20 mg PO) will be administered approximately 30 minutes before initiation of chemotherapy. Subjects will continue to receive granisetron (2 mg daily) on Days 2 and 3. 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 and neurological examinations, vital signs, electrocardiograms (ECGs), and safety laboratory values including BUN and creatinine. All subjects are expected to complete Cycle 1 and will have the option of participating in up to five additional cycles. Blood samples may be collected and stored in this study and may be analyzed for future biomarker research related to safety and efficacy.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	1369 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 and Efficacy of Rolapitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting (CINV) in Subjects Receiving Moderately Emetogenic Chemotherapy
Study Start Date :	February 2012
Actual Primary Completion Date :	February 2014
Actual Study Completion Date :	February 2014

Arms and Interventions

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Arm	Intervention/treatment
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.	Drug: Granisetron; 2 mg PO; Other Names: Kytril; Granisol Drug: Dexamethasone; 20 mg PO; Other Name: Decadron Drug: Placebo; (4 X 0 mg capsules) 0 mg PO; Other Name: Placebo to match Rolapitant
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.	Drug: Rolapitant; (4 X 50 mg capsule) 200 mg PO; Other Name: Varubi Drug: Granisetron; 2 mg PO; Other Names: Kytril; Granisol Drug: Dexamethasone; 20 mg PO; Other Name: Decadron

Outcome Measures

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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 MEC. 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 :

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 rate in the overall (0 to 120 hours) phase of CINV.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
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
• 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.

Contacts and Locations

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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

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

Schwartzberg LS, Modiano MR, Rapoport BL, Chasen MR, Gridelli C, Urban L, Poma A, Arora S, Navari RM, Schnadig ID. Safety and efficacy of rolapitant for prevention of chemotherapy-induced nausea and vomiting after administration of moderately emetogenic chemotherapy or anthracycline and cyclophosphamide regimens in patients with cancer: a randomised, active-controlled, double-blind, phase 3 trial. Lancet Oncol. 2015 Sep;16(9):1071-1078. doi: 10.1016/S1470-2045(15)00034-0. Epub 2015 Aug 10.

Responsible Party:	Tesaro, Inc.
ClinicalTrials.gov Identifier:	NCT01500226 History of Changes
Other Study ID Numbers:	TS-P04834
First Posted:	December 28, 2011
Results First Posted:	November 4, 2015
Last Update Posted:	March 2, 2016
Last Verified:	July 2014

Keywords provided by Tesaro, Inc.:

Rolapitant; Nausea; Vomiting; CINV; Chemotherapy

Additional relevant MeSH terms:

Nausea; Vomiting; Signs and Symptoms, Digestive; Signs and Symptoms; Dexamethasone acetate; Dexamethasone; Granisetron; BB 1101; 8-((1-(3,5-bis(trifluoromethyl)phenyl)ethoxy)methyl)-8-phenyl-1,7-diazaspiro(4,5)decan-2-one; Emetics; 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; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Serotonin Antagonists; Serotonin Agents; Neurotransmitter Agents; Neurokinin-1 Receptor Antagonists