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

NCT01500213 | Completed Phase 3 Results

• 1 other identifier: TS-P04833
• Study Type: interventional
• Target: 555
• Locations: 1 country
• Sites: 1

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.

Conditions

Chemotherapy-induced Nausea and Vomiting

Keywords

Rolapitant; Nausea; Vomiting; CINV; Chemotherapy

Outcome Measures

Primary Outcomes (1)

• 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 emesis and no rescue medication) in the delayed phase (\>24 to 120 hours).

  >24 to 120 hours post chemotherapy

Secondary Outcomes (2)

• Acute Phase Response

  0 to 24 hours

• Overall Response Rate

  0 to 120 hours

Study Arms (2)

Placebo + Granisetron + Dexamethasone

PLACEBO COMPARATOR

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; Drug: Dexamethasone; Drug: Placebo

Rolapitant

EXPERIMENTAL

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; Drug: Granisetron; Drug: Dexamethasone

Interventions

Rolapitant DRUG

200 mg PO

Also known as: Varubi

Rolapitant

Granisetron DRUG

10 mcg/kg IV

Also known as: Kytril, Granisol

Placebo + Granisetron + Dexamethasone; Rolapitant

Dexamethasone DRUG

20 mg PO and 8 mg PO

Also known as: Decadron

Placebo + Granisetron + Dexamethasone; Rolapitant

Placebo DRUG

(4 X 0 mg capsules) o mg PO

Also known as: Placebo to match Rolapitant

Placebo + Granisetron + Dexamethasone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Tesaro, Inc.: lead

Study Sites (1)

TESARO Inc

Waltham, Massachusetts, 02451, United States

Location

Related Publications (1)

• 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.

  PMID: 26272769 DERIVED

MeSH Terms

Conditions

Vomiting; Nausea

Interventions

rolapitant; Granisetron; Dexamethasone; Calcium Dobesilate

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Results Point of Contact

• Title: Martin Huber, M.D., Senior Vice President and Chief Medical Officer
• Organization: Tesaro

mhuber@tesarobio.com

862.228.2483

Study Officials

• Dennis Vargo, MD

  Tesaro, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2011
• First Posted: December 28, 2011
• Study Start: February 1, 2012
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: March 2, 2016
• Results First Posted: November 4, 2015

Record last verified: 2015-03

Locations

US (1)