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

• ClinicalTrials.gov Identifier: NCT01500226
• Recruitment Status: Completed
• First Posted: December 28, 2011
• Results First Posted: November 4, 2015
• Last Update Posted: March 2, 2016
• Sponsor: Tesaro, Inc.
• Information provided by (Responsible Party): Tesaro, Inc.

Tracking Information

• First Submitted Date: December 22, 2011
• First Posted Date: December 28, 2011
• Results First Submitted Date: October 2, 2015
• Results First Posted Date: November 4, 2015
• Last Update Posted Date: March 2, 2016
• Study Start Date: February 2012
• Actual Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 2, 2015)

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).

Original Primary Outcome Measures (submitted: December 27, 2011)

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 emetic episodes and no rescue medication) in the delayed phase (>24 to 120 hours).

Current Secondary Outcome Measures (submitted: October 2, 2015)

• 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.
• 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.

Original Secondary Outcome Measures (submitted: December 27, 2011)

• 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.
• 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.
• Safety and Tolerability [ Time Frame: 30 days post study drug ]
  To evaluate the safety and tolerability of rolapitant in subjects receiving HEC as assessed by the incidence and severity of AEs.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Ph 3 Safety/Efficacy Study of Rolapitant for Prevention of CINV in Subjects Receiving Moderately Emetogenic Chemotherapy
• 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
• 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.
• 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 Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Prevention
• Condition: Chemotherapy-induced Nausea and Vomiting

Intervention

• 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
• Drug: Placebo
  (4 X 0 mg capsules) 0 mg PO
  Other Name: Placebo to match Rolapitant

Study Arms

• 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.
  Interventions:

  • Drug: Granisetron
  • Drug: Dexamethasone
  • Drug: Placebo
• 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.
  Interventions:

  • Drug: Rolapitant
  • Drug: Granisetron
  • Drug: Dexamethasone

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 27, 2013): 1369
• Original Estimated Enrollment (submitted: December 27, 2011): 1350
• Actual Study Completion Date: February 2014
• Actual Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01500226
• Other Study ID Numbers: TS-P04834
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Tesaro, Inc.
• Study Sponsor: Tesaro, Inc.
• Collaborators: Not Provided

Investigators

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

• PRS Account: Tesaro, Inc.
• Verification Date: July 2014