Phase 3 Safety and Efficacy Study of Rolapitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting (CINV) in Subjects Receiving Highly Emetogenic Chemotherapy (HEC)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Tesaro, Inc.
ClinicalTrials.gov Identifier:
NCT01499849
First received: December 20, 2011
Last updated: July 11, 2014
Last verified: October 2012
  Purpose

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 Intervention Phase
Chemotherapy-induced Nausea and Vomiting
Drug: Rolapitant
Drug: Granisetron
Drug: dexamethasone
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: A 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 Highly Emetogenic Chemotherapy (HEC)

Resource links provided by NLM:


Further study details as provided by Tesaro, Inc.:

Primary Outcome Measures:
  • No Emetic Episodes and No Rescue Medication [ Time Frame: >24 to 120 hours post chemotherapy ] [ Designated as safety issue: No ]
    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 [ Time Frame: 0 to 24 hours ] [ Designated as safety issue: No ]
    To determine the effect of rolapitant on complete response rates in the acute (0 to 24 hours)phase of CINV

  • Overall Response Rate [ Time Frame: 0 to 120 hours ] [ Designated as safety issue: No ]
    To determine the effect of rolapitant on complete response rates in the overall (0 to 120 hours) phase of CINV.

  • Safety and Tolerability [ Time Frame: 30 days post study drug ] [ Designated as safety issue: No ]
    To evaluate the safety and tolerability of rolapitant in subjects receiving HEC as assessed by the incidence and severity of AEs.


Enrollment: 532
Study Start Date: February 2012
Study Completion Date: May 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
200
Drug: Granisetron
10 mcg/kg IV
Drug: dexamethasone
20 mg PO and 8 mg PO
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
Drug: dexamethasone
20 mg PO and 8 mg PO

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01499849

Locations
United States, Massachusetts
TESARO Inc
Waltham, Massachusetts, United States, 02451
Sponsors and Collaborators
Tesaro, Inc.
Investigators
Study Director: Allen Poma, MD Tesaro, Inc.
  More Information

No publications provided

Responsible Party: Tesaro, Inc.
ClinicalTrials.gov Identifier: NCT01499849     History of Changes
Other Study ID Numbers: TS-P04832
Study First Received: December 20, 2011
Last Updated: July 11, 2014
Health Authority: United States: Food and Drug Administration

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
Dexamethasone 21-phosphate
BB 1101
Emetics
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
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

ClinicalTrials.gov processed this record on July 28, 2014