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

• ClinicalTrials.gov Identifier: NCT01499849
• Recruitment Status: Completed
• First Posted: December 26, 2011
• Results First Posted: November 4, 2015
• Last Update Posted: May 19, 2016
• Sponsor: Tesaro, Inc.
• Information provided by (Responsible Party): Tesaro, Inc.

Tracking Information

• First Submitted Date: December 20, 2011
• First Posted Date: December 26, 2011
• Results First Submitted Date: October 2, 2015
• Results First Posted Date: November 4, 2015
• Last Update Posted Date: May 19, 2016
• Study Start Date: February 2012
• Actual Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 22, 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 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).

• Original Primary Outcome Measures: Same as current

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

Original Secondary Outcome Measures (submitted: December 22, 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 rates 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: 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)

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.

• 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 capsules) 200 mg PO
  Other Name: Varubi
• Drug: Granisetron
  10 mcg/kg IV
  Other Names:

  • Kytril
  • Granisol
• Drug: dexamethasone
  20 mg PO and 8 mg PO
  Other Name: Decadron
• Drug: Placebo
  (4 X 0 mg capsules) 0 mg PO
  Other Name: Placebo to match Rolapitant

Study Arms

• 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.
  Interventions:

  • Drug: Rolapitant
  • Drug: Granisetron
  • Drug: dexamethasone
• 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.
  Interventions:

  • Drug: Granisetron
  • Drug: dexamethasone
  • Drug: Placebo

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 1, 2014): 532
• Original Estimated Enrollment (submitted: December 22, 2011): 530
• Actual Study Completion Date: May 2014
• Actual Primary Completion Date: May 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
• 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.

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: NCT01499849
• Other Study ID Numbers: TS-P04832
• 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: October 2012