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

Primary Purpose

Chemotherapy-induced Nausea and Vomiting

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Rolapitant
Granisetron
dexamethasone
Placebo
Sponsored by
Tesaro, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Chemotherapy-induced Nausea and Vomiting focused on measuring Rolapitant, Nausea, Vomiting, CINV, Chemotherapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • TESARO Inc

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Rolapitant

Placebo + Granisetron + Dexamethasone

Arm Description

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.

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

Outcomes

Primary Outcome Measures

No Emetic Episodes and No Rescue Medication
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

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

Full Information

First Posted
December 20, 2011
Last Updated
April 19, 2016
Sponsor
Tesaro, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01499849
Brief Title
Ph3 Safety/Efficacy Study of Rolapitant for the Prevention of CINV in Subjects Receiving Highly Emetogenic Chemotherapy
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 Type
Interventional

2. Study Status

Record Verification Date
October 2012
Overall Recruitment Status
Completed
Study Start Date
February 2012 (undefined)
Primary Completion Date
May 2014 (Actual)
Study Completion Date
May 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tesaro, Inc.

4. Oversight

Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chemotherapy-induced Nausea and Vomiting
Keywords
Rolapitant, Nausea, Vomiting, CINV, Chemotherapy

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
532 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Rolapitant
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo + Granisetron + Dexamethasone
Arm Type
Placebo Comparator
Arm Description
Day 1: Placebo + Granisetron (10 mcg/kg IV)+ dexamethasone (20 mg PO) Days 2-4: Dexamethasone (8 mg PO) will be administered orally BID.
Intervention Type
Drug
Intervention Name(s)
Rolapitant
Other Intervention Name(s)
Varubi
Intervention Description
(4 X 50 mg capsules) 200 mg PO
Intervention Type
Drug
Intervention Name(s)
Granisetron
Other Intervention Name(s)
Kytril, Granisol
Intervention Description
10 mcg/kg IV
Intervention Type
Drug
Intervention Name(s)
dexamethasone
Other Intervention Name(s)
Decadron
Intervention Description
20 mg PO and 8 mg PO
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Placebo to match Rolapitant
Intervention Description
(4 X 0 mg capsules) 0 mg PO
Primary Outcome Measure Information:
Title
No Emetic Episodes and No Rescue Medication
Description
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).
Time Frame
>24 to 120 hours post chemotherapy
Secondary Outcome Measure Information:
Title
Acute Phase Response
Description
To determine the effect of rolapitant on complete response rates in the acute (0 to 24 hours)phase of CINV
Time Frame
0 to 24 hours
Title
Overall Response Rate
Description
To determine the effect of rolapitant on complete response rates in the overall (0 to 120 hours) phase of CINV.
Time Frame
0 to 120 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dennis Vargo, MD
Organizational Affiliation
Tesaro, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
TESARO Inc
City
Waltham
State/Province
Massachusetts
ZIP/Postal Code
02451
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
26272769
Citation
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.
Results Reference
derived

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

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