Clinical trial NCT01500226: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chemotherapy-induced Nausea and Vomiting
Keywords: Rolapitant
Nausea
Vomiting
CINV
Chemotherapy
Lead sponsor: Tesaro, Inc.
Sponsor class: INDUSTRY
First posted: 2011-12-28
Enrollment: 1369
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: No Emetic Episodes and No Rescue Medication
timeFrame: >24 to 120 hours post chemotherapy
Secondary outcomes:
measure: Acute Phase Response
timeFrame: 0 to 24 hours
measure: Overall Response Rate
timeFrame: 0 to 120 hours
Other outcomes:
Locations:
city: Waltham
country: United States
facility: TESARO Inc
state: Massachusetts
Study officials:
affiliation: Tesaro, Inc.
name: Dennis Vargo, MD
role: STUDY_DIRECTOR
References:
citation: 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.