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Efficacy and Safety of Fosaprepitant Dimeglumine in Preventing Chemotherapy-Induced Nausea and Vomiting (MK-0517-031)

Primary Purpose

Chemotherapy-Induced Nausea and Vomiting (CINV)

Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Fosaprepitant dimeglumine
Fosaprepitant Placebo
Dexamethasone
Ondansetron
Dexamethasone Placebo
Ondansetron Placebo
Rescue Therapy
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Chemotherapy-Induced Nausea and Vomiting (CINV) focused on measuring NK-1 Receptor Antagonist, CINV, Emesis, MEC

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    Fosaprepitant Regimen

    Control Regimen

    Arm Description

    On Day 1, participants received fosaprepitant, 150 mg intravenous (IV) infusion, ~30 minutes prior to chemotherapy PLUS dexamethasone 12 mg, orally (PO) ~30 minutes prior to chemotherapy PLUS ondansetron 16 mg total dose: 8 mg PO ~30-60 minutes prior to chemotherapy, followed by 8 mg PO, 8 hours after first dose PLUS dexamethasone placebo, PO ~30 minutes prior to chemotherapy. On Days 2 and 3, participants received ondansetron placebo, PO every 12 hours. Rescue Therapy: For established cases of nausea or vomiting, medications may have been prescribed from these permitted choices: 5-HT3 antagonists (granisetron, dolasetron, tropisetron or ondansetron); phenothiazines (e.g. prochlorperazine, fluphenazine, perphenazine, thiethylperazine, or chlorpromazine); butyrophenones (e.g. haloperidol or droperidol); benzamides (e.g. metoclopramide or alizapride); benzodiazepines; corticosteroids; domperidone.

    On Day 1, participants received fosaprepitant placebo, 150 mL IV infusion, ~30 minutes prior to chemotherapy PLUS dexamethasone 20 mg, PO ~30 minutes prior to chemotherapy PLUS ondansetron 16 mg total dose: 8 mg PO ~30-60 minutes prior to chemotherapy; followed by 8 mg PO, 8 hours after the first dose. On Days 2-3, participants received ondansetron 8 mg, PO every 12 hours. Rescue Therapy: For established cases of nausea or vomiting, medications may have been prescribed from these permitted choices: 5-HT3 antagonists (granisetron, dolasetron, tropisetron or ondansetron); phenothiazines (e.g. prochlorperazine, fluphenazine, perphenazine, thiethylperazine, or chlorpromazine); butyrophenones (e.g. haloperidol or droperidol); benzamides (e.g. metoclopramide or alizapride); benzodiazepines; corticosteroids; domperidone.

    Outcomes

    Primary Outcome Measures

    Percentage of Participants With Complete Response From 25 to 120 Hours After Initiation of Moderately Emetogenic Chemotherapy (MEC)
    A Complete Response was defined as no vomiting and no use of rescue medication.
    Percentage of Participants With Infusion-site Thrombophlebitis
    The percentages of participants with infusion-site thrombophlebitis are presented. Thrombophlebitis was defined as a condition affecting a superficial vein used for an IV infusion, associated with red color, hardness upon palpation, and the presence of a tender cord and possible fever.
    Percentage of Participants With Severe Infusion-site Reactions
    The percentages of participants with severe infusion-site reactions, including severe site pain, or severe site redness (erythema) or severe site hardness (induration) are presented.

    Secondary Outcome Measures

    Percentage of Participants With Complete Response From 0 to 120 Hours After Initiation of MEC
    A Complete Response was defined as no vomiting and no use of rescue medication.
    Percentage of Participants With Complete Response From 0 to 24 Hours After Initiation of MEC
    A Complete Response was defined as no vomiting and no use of rescue medication.
    Percentage of Participants With No Vomiting From 0 to 120 Hours After Initiation of MEC
    No Vomiting was defined as no emetic (vomiting) episodes, including no vomiting and no retching or dry heaves (attempts to vomit that are not productive of stomach contents), regardless of use of rescue medication.

    Full Information

    First Posted
    April 24, 2012
    Last Updated
    August 2, 2018
    Sponsor
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01594749
    Brief Title
    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

    2. Study Status

    Record Verification Date
    August 2018
    Overall Recruitment Status
    Completed
    Study Start Date
    September 24, 2012 (Actual)
    Primary Completion Date
    November 3, 2014 (Actual)
    Study Completion Date
    November 3, 2014 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Merck Sharp & Dohme LLC

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    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).

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Chemotherapy-Induced Nausea and Vomiting (CINV)
    Keywords
    NK-1 Receptor Antagonist, CINV, Emesis, MEC

    7. Study Design

    Primary Purpose
    Prevention
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    1015 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Fosaprepitant Regimen
    Arm Type
    Experimental
    Arm Description
    On Day 1, participants received fosaprepitant, 150 mg intravenous (IV) infusion, ~30 minutes prior to chemotherapy PLUS dexamethasone 12 mg, orally (PO) ~30 minutes prior to chemotherapy PLUS ondansetron 16 mg total dose: 8 mg PO ~30-60 minutes prior to chemotherapy, followed by 8 mg PO, 8 hours after first dose PLUS dexamethasone placebo, PO ~30 minutes prior to chemotherapy. On Days 2 and 3, participants received ondansetron placebo, PO every 12 hours. Rescue Therapy: For established cases of nausea or vomiting, medications may have been prescribed from these permitted choices: 5-HT3 antagonists (granisetron, dolasetron, tropisetron or ondansetron); phenothiazines (e.g. prochlorperazine, fluphenazine, perphenazine, thiethylperazine, or chlorpromazine); butyrophenones (e.g. haloperidol or droperidol); benzamides (e.g. metoclopramide or alizapride); benzodiazepines; corticosteroids; domperidone.
    Arm Title
    Control Regimen
    Arm Type
    Active Comparator
    Arm Description
    On Day 1, participants received fosaprepitant placebo, 150 mL IV infusion, ~30 minutes prior to chemotherapy PLUS dexamethasone 20 mg, PO ~30 minutes prior to chemotherapy PLUS ondansetron 16 mg total dose: 8 mg PO ~30-60 minutes prior to chemotherapy; followed by 8 mg PO, 8 hours after the first dose. On Days 2-3, participants received ondansetron 8 mg, PO every 12 hours. Rescue Therapy: For established cases of nausea or vomiting, medications may have been prescribed from these permitted choices: 5-HT3 antagonists (granisetron, dolasetron, tropisetron or ondansetron); phenothiazines (e.g. prochlorperazine, fluphenazine, perphenazine, thiethylperazine, or chlorpromazine); butyrophenones (e.g. haloperidol or droperidol); benzamides (e.g. metoclopramide or alizapride); benzodiazepines; corticosteroids; domperidone.
    Intervention Type
    Drug
    Intervention Name(s)
    Fosaprepitant dimeglumine
    Other Intervention Name(s)
    EMEND for Injection, MK-0517
    Intervention Type
    Drug
    Intervention Name(s)
    Fosaprepitant Placebo
    Intervention Type
    Drug
    Intervention Name(s)
    Dexamethasone
    Other Intervention Name(s)
    Decadron
    Intervention Type
    Drug
    Intervention Name(s)
    Ondansetron
    Other Intervention Name(s)
    Zofran
    Intervention Type
    Drug
    Intervention Name(s)
    Dexamethasone Placebo
    Intervention Type
    Drug
    Intervention Name(s)
    Ondansetron Placebo
    Intervention Type
    Drug
    Intervention Name(s)
    Rescue Therapy
    Primary Outcome Measure Information:
    Title
    Percentage of Participants With Complete Response From 25 to 120 Hours After Initiation of Moderately Emetogenic Chemotherapy (MEC)
    Description
    A Complete Response was defined as no vomiting and no use of rescue medication.
    Time Frame
    25 to 120 hours after initiation of MEC
    Title
    Percentage of Participants With Infusion-site Thrombophlebitis
    Description
    The percentages of participants with infusion-site thrombophlebitis are presented. Thrombophlebitis was defined as a condition affecting a superficial vein used for an IV infusion, associated with red color, hardness upon palpation, and the presence of a tender cord and possible fever.
    Time Frame
    Day 1 through Day 17, inclusive
    Title
    Percentage of Participants With Severe Infusion-site Reactions
    Description
    The percentages of participants with severe infusion-site reactions, including severe site pain, or severe site redness (erythema) or severe site hardness (induration) are presented.
    Time Frame
    Day 1 through Day 17, inclusive
    Secondary Outcome Measure Information:
    Title
    Percentage of Participants With Complete Response From 0 to 120 Hours After Initiation of MEC
    Description
    A Complete Response was defined as no vomiting and no use of rescue medication.
    Time Frame
    0 to 120 hours after initiation of MEC
    Title
    Percentage of Participants With Complete Response From 0 to 24 Hours After Initiation of MEC
    Description
    A Complete Response was defined as no vomiting and no use of rescue medication.
    Time Frame
    0 to 24 hours after initiation of MEC
    Title
    Percentage of Participants With No Vomiting From 0 to 120 Hours After Initiation of MEC
    Description
    No Vomiting was defined as no emetic (vomiting) episodes, including no vomiting and no retching or dry heaves (attempts to vomit that are not productive of stomach contents), regardless of use of rescue medication.
    Time Frame
    0 to 120 hours after initiation of MEC

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    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.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Medical Director
    Organizational Affiliation
    Merck Sharp & Dohme LLC
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
    IPD Sharing URL
    http://engagezone.msd.com/ds_documentation.php
    Citations:
    PubMed Identifier
    26449391
    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.
    Results Reference
    result
    PubMed Identifier
    32988373
    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.
    Results Reference
    derived
    PubMed Identifier
    29808377
    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.
    Results Reference
    derived
    Available IPD and Supporting Information:
    Available IPD/Information Type
    CSR Synopsis
    Available IPD/Information URL
    http://www.merck.com/clinical-trials/study.html?id=0517-031&kw=0517-031&tab=access

    Learn more about this trial

    Efficacy and Safety of Fosaprepitant Dimeglumine in Preventing Chemotherapy-Induced Nausea and Vomiting (MK-0517-031)

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