Clinical trial NCT01594749: Efficacy and Safety of Fosaprepitant Dimeglumine in Preventing Chemotherapy-Induced Nausea and Vomiting (MK-0517-031)
Official title: A Phase III, Randomized, Double-Blind, Active Comparator-Controlled Parallel-Group Study, Conducted Under In-House Blinding Conditions, to Examine the Efficacy and Safety of a Single 150 mg Dose of Intravenous Fosaprepitant Dimeglumine for the Prevention of Chemotherapy-Induced Nausea and Vomiting (CINV) Associated With Moderately Emetogenic Chemotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chemotherapy-Induced Nausea and Vomiting (CINV)
Keywords: NK-1 Receptor Antagonist, CINV, Emesis, MEC
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2012-05-09
Enrollment: 1015
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 study aims to demonstrate that, when given concomitantly with a 5-hydroxytryptamine 3 (5-HT3) antagonist and a corticosteroid, a single 150 mg intravenous (IV) dose of fosaprepitant given on Day 1 is superior to the control regimen of 5-HT3 antagonist and corticosteroid only, in preventing chemotherapy-induced nausea and vomiting (CINV) associated with moderately emetogenic chemotherapy (MEC).


Eligibility criteria: Inclusion Criteria:

* Has a histologically or cytologically confirmed malignant disease
* Is naive to moderately and highly emetogenic chemotherapy
* Is scheduled to receive a single IV dose of one or more MEC agents on Day 1, except for the combination of anthracycline and cyclophosphamide
* Has a predicted life expectancy of at least 4 months, and a Karnofsky score of at least 60 indicating that the participant requires occasional assistance, but is able to care for most of his/her needs.
* Female of childbearing potential demonstrates a negative urine pregnancy test, and agrees to remain abstinent or use two acceptable forms of birth control for at least 14 days prior to study, throughout the study, and at least 1 month following last dose of study drug.

Exclusion Criteria:

* Has vomited in the 24 hours prior to treatment Day 1
* Has symptomatic primary or metastatic symptomatic central nervous system malignancy causing nausea and/or vomiting
* Is scheduled to receive chemotherapy agent classified as highly emetogenic
* Has received or will receive total body irradiation, or radiation therapy to the abdomen, pelvis, head and neck in the week prior to Treatment Days 1 through Day 6 of the Treatment Period
* Has illness or history of illness which might confound study results or pose unwarranted risk
* Known history of QT interval prolongation
* Uses illicit drugs or abuses alcohol
* Mentally incapacitated or has a significant emotional or psychiatric disorder
* History of hypersensitivity to aprepitant, ondansetron or dexamethasone
* Pregnant or breast-feeding
* Has participated in a study with aprepitant or taken a non-approved (investigational) drug within the last 4 weeks
* Has concurrent condition, such as systemic fungal infection or uncontrolled diabetes, that precludes administration of dexamethasone.

Primary outcomes:
measure: Percentage of Participants With Complete Response From 25 to 120 Hours After Initiation of Moderately Emetogenic Chemotherapy (MEC)
timeFrame: 25 to 120 hours after initiation of MEC
measure: Percentage of Participants With Infusion-site Thrombophlebitis
timeFrame: Day 1 through Day 17, inclusive
measure: Percentage of Participants With Severe Infusion-site Reactions
timeFrame: Day 1 through Day 17, inclusive
Secondary outcomes:
measure: Percentage of Participants With Complete Response From 0 to 120 Hours After Initiation of MEC
timeFrame: 0 to 120 hours after initiation of MEC
measure: Percentage of Participants With Complete Response From 0 to 24 Hours After Initiation of MEC
timeFrame: 0 to 24 hours after initiation of MEC
measure: Percentage of Participants With No Vomiting From 0 to 120 Hours After Initiation of MEC
timeFrame: 0 to 120 hours after initiation of MEC
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Weinstein C, Jordan K, Green SA, Camacho E, Khanani S, Beckford-Brathwaite E, Vallejos W, Liang LW, Noga SJ, Rapoport BL. Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with moderately emetogenic chemotherapy: results of a randomized, double-blind phase III trial. Ann Oncol. 2016 Jan;27(1):172-8. doi: 10.1093/annonc/mdv482. Epub 2015 Oct 8.
citation: Weinstein C, Jordan K, Green S, Khanani S, Beckford-Brathwaite E, Vallejos W, Pong A, Noga SJ, Rapoport BL. Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting in patients receiving moderately emetogenic chemotherapy regimens: a subgroup analysis from a randomized clinical trial of response in subjects by cancer type. BMC Cancer. 2020 Sep 25;20(1):918. doi: 10.1186/s12885-020-07259-5.
citation: Weinstein C, Jordan K, Green SA, Camacho E, Khanani S, Beckford-Brathwaite E, Pong A, Noga SJ, Rapoport BL. Evaluation of factors contributing to the response to fosaprepitant in a heterogeneous, moderately emetogenic chemotherapy population: an exploratory analysis of a randomized phase III trial. Support Care Cancer. 2018 Nov;26(11):3773-3780. doi: 10.1007/s00520-018-4242-x. Epub 2018 May 28.