Back to resultsA Korean Study of Efficacy and Safety of Aprepitant-based Triple Regimen for the Prevention of Chemotherapy-Induced Nausea and Vomiting in the First Cycle of Moderately Emetogenic Chemotherapy (Non-doxorubicin Hydrochloride [Adriamycin] and Cyclophosphamide Regimens) (MK-0869-225) (KMEC) (KMEC)
Primary Purpose
Nausea, Vomiting
Status
Completed
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Aprepitant
Aprepitant Placebo
Ondansetron
Dexamethasone
Ondansetron Placebo
Rescue Therapy (granisetron, dolasetron, tropisetron or ondansetron; metoclopramide or alizapride).
Sponsored by
About this trial
This is an interventional treatment trial for Nausea focused on measuring chemotherapy, nausea, vomiting, emetogenic, cancer, antiemetics, tumor
Eligibility Criteria
Inclusion Criteria:
- Histologically or cytologically confirmed malignant disease
- Scheduled to receive a single dose of one or more of moderately emetogenic chemotherapeutic agents during Cycle 1
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2 or Karnofsky score ≥60
- Predicted life span ≥4 months
- Laboratory values demonstrating adequate hematologic status
- Premenopausal females must not be pregnant or lactating and must agree to use effective birth control
Exclusion Criteria:
- Received chemotherapy within 6 months prior to starting on study drugs
- Scheduled to receive subsequent treatment due to a refractory response to first or second line chemotherapy
- Received an investigational drug within 30 days prior to starting on study drugs
- Radiation therapy to the abdomen or pelvis in the week prior to starting on study drugs
- Vomiting in the 24 hours prior to starting on study drugs
- Active infection (e.g., pneumonia) or any uncontrolled disease (e.g., diabetic ketoacidosis, gastrointestinal obstruction) except for malignancy
- Known hypersensitivity to Aprepitant (EMEND®), Dexamethasone or 5-HT3 receptor antagonists
- Presentation with gastrointestinal obstruction symptoms
- Symptomatic primary or metastatic central nervous system malignancy
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Aprepitant Regimen
Control Regimen
Arm Description
Participants receive one aprepitant 125 mg capsule by mouth (PO) once daily (QD) on Day 1 and one aprepitant 80 mg capsule PO QD on Days 2 and 3 of Cycle 1. Participants also receive ondansetron 16 mg intravenously (IV) QD and dexamethasone 12 mg PO on Day 1 and placebo for ondansetron 8 mg PO twice daily (BID) on Days 2 and 3.
Participants receive one placebo capsule PO QD on Day 1 and one placebo capsule PO QD on Days 2 and 3 of Cycle 1. Participants also receive ondansetron 16 mg IV QD and dexamethasone 20 mg PO on Day 1 and ondansetron 8 mg PO BID on Days 2 and 3.
Outcomes
Primary Outcome Measures
The Percentage of Participants With No Vomiting - Overall Stage
A vomiting episode was defined as one or more episodes of emesis (expulsion of stomach contents through the mouth) or retches (an attempt to vomit that is not productive of stomach contents). No vomiting during the Overall Stage was defined as no episodes of emesis during the 120 hours (Days 1-5) after initiation of moderately emetogenic chemotherapy (MEC).
Secondary Outcome Measures
Percentage of Participants With a Complete Response - Overall, Acute, and Delayed Stages
A Complete Response was defined as no vomiting or dry heaves and no use of a rescue therapy. Overall Stage=0 to 120 hours after initiation of MEC. Acute Stage=0 to 24 hours after initiation of MEC. Delayed Stage=25 to 120 hours after initiation of MEC.
Number of Emetic Events - Overall Stage
The number of emetic events that occurred during the Overall Stage (0 to 120 hours after initiation of MEC) are presented.
Percentage of Participants With No Vomiting and No Significant Nausea - Overall Stage
Nausea was to be assessed using a 100-mm horizontal visual analogue scale (VAS) located in the participant diary labeled: "How much nausea have you had over the last 24 hours?" The left end of the scale (0 mm) was labeled "no nausea," and the right end of the scale (100 mm) is labeled "nausea as bad as it could be." In this study, No Significant Nausea was defined as a VAS nausea rating <25 mm.
Percentage of Participants With No Impact on Daily Life - Overall Stage
The Functional Living Index-Emesis questionnaire (FLIE) is a validated, participant-reported instrument to measure the impact of chemotherapy-induced nausea and vomiting on daily life. There are 9 nausea-related items and 9 vomiting-related items, each on a 7-point scale. For the purposes of this study, "No Impact" on daily life was defined as an average item score of >6 on the 7-point scale; a total score >108 indicates no impact on daily life. Overall Stage=0 to 120 hours after initiation of MEC.
Number of Participants With No Use of a Rescue Therapy - Overall, Acute, and Delayed Stages
The percentage of participants who used no rescue therapy after initiation of MEC is presented for the Overall, Acute and Delayed Stages. Overall Stage=0 to 120 hours after initiation of MEC. Acute Stage=0 to 24 hours after initiation of MEC. Delayed Stage=25 to 120 hours after initiation of MEC.
Percentage of Participants With One or More Clinical Adverse Event
An adverse event was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the study drug. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition, which is temporally associated with the use of the study drug, is also an adverse event. Nausea and vomiting experienced during Days 1-6 were not counted as adverse events unless they were reported as a serious adverse event.
Percentage of Participants With No Vomiting - Acute and Delayed Stages
A vomiting episode was defined as one or more episodes of emesis (expulsion of stomach contents through the mouth) or retches (an attempt to vomit that is not productive of stomach contents). Acute Stage=0 to 24 hours after initiation of MEC. Delayed Stage=25 to 120 hours after initiation of MEC.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01636947
Brief Title
A Korean Study of Efficacy and Safety of Aprepitant-based Triple Regimen for the Prevention of Chemotherapy-Induced Nausea and Vomiting in the First Cycle of Moderately Emetogenic Chemotherapy (Non-doxorubicin Hydrochloride [Adriamycin] and Cyclophosphamide Regimens) (MK-0869-225) (KMEC)
Acronym
KMEC
Official Title
A Korean Multicenter, Randomized, Double-Blind, Clinical Trial to Evaluate the Efficacy and Tolerability of Aprepitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting in the First Cycle of Moderately Emetogenic Chemotherapies (MEC, Non-AC Regimes) With Broad Range of Tumor Types (KMEC Study)
Study Type
Interventional
2. Study Status
Record Verification Date
August 2018
Overall Recruitment Status
Completed
Study Start Date
December 12, 2012 (Actual)
Primary Completion Date
August 4, 2014 (Actual)
Study Completion Date
August 4, 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is an efficacy and safety study to compare aprepitant with ondansetron for the prevention of nausea and vomiting in the first cycle of moderately emetogenic chemotherapy (MEC) in participants with solid tumors. MECs include a number of commonly used cancer chemotherapeutic drugs including: oxaliplatin-based, irinotecan-based, and carboplatin-based regimens.
The primary hypothesis of this study is that the Aprepitant Regimen is superior to the Control (ondansetron) Regimen with respect to the percentage of participants with No Vomiting Overall (in the 120 hours following initiation of MEC) in participants with solid tumors.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nausea, Vomiting
Keywords
chemotherapy, nausea, vomiting, emetogenic, cancer, antiemetics, tumor
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
494 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Aprepitant Regimen
Arm Type
Experimental
Arm Description
Participants receive one aprepitant 125 mg capsule by mouth (PO) once daily (QD) on Day 1 and one aprepitant 80 mg capsule PO QD on Days 2 and 3 of Cycle 1. Participants also receive ondansetron 16 mg intravenously (IV) QD and dexamethasone 12 mg PO on Day 1 and placebo for ondansetron 8 mg PO twice daily (BID) on Days 2 and 3.
Arm Title
Control Regimen
Arm Type
Active Comparator
Arm Description
Participants receive one placebo capsule PO QD on Day 1 and one placebo capsule PO QD on Days 2 and 3 of Cycle 1. Participants also receive ondansetron 16 mg IV QD and dexamethasone 20 mg PO on Day 1 and ondansetron 8 mg PO BID on Days 2 and 3.
Intervention Type
Drug
Intervention Name(s)
Aprepitant
Other Intervention Name(s)
MK-0869, EMEND® PO
Intervention Description
Aprepitant (125 mg PO, QD) on Day 1, Aprepitant (80 mg PO, QD) on Days 2 and 3
Intervention Type
Drug
Intervention Name(s)
Aprepitant Placebo
Intervention Description
Aprepitant Placebo (PO, QD) on Days 1, 2, and 3
Intervention Type
Drug
Intervention Name(s)
Ondansetron
Other Intervention Name(s)
ZOFRAN®
Intervention Description
Ondansetron (16 mg, IV, QD) on Day 1 and/or ondansetron (8 mg PO BID) on Days 2 and 3
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Other Intervention Name(s)
dexamethasone sodium phosphate, dexamethasone acetate, Decadron, Dexasone, Diodex, Hexadrol, Maxidex
Intervention Description
Dexamethasone (20 mg or 12 mg, PO) on Day 1
Intervention Type
Drug
Intervention Name(s)
Ondansetron Placebo
Intervention Description
Ondansetron Placebo (PO, BID) on Days 2 and 3
Intervention Type
Drug
Intervention Name(s)
Rescue Therapy (granisetron, dolasetron, tropisetron or ondansetron; metoclopramide or alizapride).
Intervention Description
Use of a rescue therapy for nausea and vomiting is permitted throughout the study. Permitted rescue therapies include a drug from among the following classes: 5-hydroxytryptamine (5-HT3) antagonists (granisetron, dolasetron, tropisetron or ondansetron), benzodiazepines, or benzamides (e.g., metoclopramide or alizapride).
Primary Outcome Measure Information:
Title
The Percentage of Participants With No Vomiting - Overall Stage
Description
A vomiting episode was defined as one or more episodes of emesis (expulsion of stomach contents through the mouth) or retches (an attempt to vomit that is not productive of stomach contents). No vomiting during the Overall Stage was defined as no episodes of emesis during the 120 hours (Days 1-5) after initiation of moderately emetogenic chemotherapy (MEC).
Time Frame
Hour 0 on Day 1 to Day 5 (approximately 120 hours)
Secondary Outcome Measure Information:
Title
Percentage of Participants With a Complete Response - Overall, Acute, and Delayed Stages
Description
A Complete Response was defined as no vomiting or dry heaves and no use of a rescue therapy. Overall Stage=0 to 120 hours after initiation of MEC. Acute Stage=0 to 24 hours after initiation of MEC. Delayed Stage=25 to 120 hours after initiation of MEC.
Time Frame
Hour 0 on Day 1 to Day 5 (approximately 120 hours)
Title
Number of Emetic Events - Overall Stage
Description
The number of emetic events that occurred during the Overall Stage (0 to 120 hours after initiation of MEC) are presented.
Time Frame
Hour 0 on Day 1 to Day 5 (approximately 120 hours)
Title
Percentage of Participants With No Vomiting and No Significant Nausea - Overall Stage
Description
Nausea was to be assessed using a 100-mm horizontal visual analogue scale (VAS) located in the participant diary labeled: "How much nausea have you had over the last 24 hours?" The left end of the scale (0 mm) was labeled "no nausea," and the right end of the scale (100 mm) is labeled "nausea as bad as it could be." In this study, No Significant Nausea was defined as a VAS nausea rating <25 mm.
Time Frame
Days 1 to Day 5
Title
Percentage of Participants With No Impact on Daily Life - Overall Stage
Description
The Functional Living Index-Emesis questionnaire (FLIE) is a validated, participant-reported instrument to measure the impact of chemotherapy-induced nausea and vomiting on daily life. There are 9 nausea-related items and 9 vomiting-related items, each on a 7-point scale. For the purposes of this study, "No Impact" on daily life was defined as an average item score of >6 on the 7-point scale; a total score >108 indicates no impact on daily life. Overall Stage=0 to 120 hours after initiation of MEC.
Time Frame
Day 6
Title
Number of Participants With No Use of a Rescue Therapy - Overall, Acute, and Delayed Stages
Description
The percentage of participants who used no rescue therapy after initiation of MEC is presented for the Overall, Acute and Delayed Stages. Overall Stage=0 to 120 hours after initiation of MEC. Acute Stage=0 to 24 hours after initiation of MEC. Delayed Stage=25 to 120 hours after initiation of MEC.
Time Frame
Day 1 to Day 5
Title
Percentage of Participants With One or More Clinical Adverse Event
Description
An adverse event was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the study drug. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition, which is temporally associated with the use of the study drug, is also an adverse event. Nausea and vomiting experienced during Days 1-6 were not counted as adverse events unless they were reported as a serious adverse event.
Time Frame
Day 1 through Day 29 (Up to 28 days after first dose of study drug)
Title
Percentage of Participants With No Vomiting - Acute and Delayed Stages
Description
A vomiting episode was defined as one or more episodes of emesis (expulsion of stomach contents through the mouth) or retches (an attempt to vomit that is not productive of stomach contents). Acute Stage=0 to 24 hours after initiation of MEC. Delayed Stage=25 to 120 hours after initiation of MEC.
Time Frame
Day 1, Day 2 to Day 5
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically or cytologically confirmed malignant disease
Scheduled to receive a single dose of one or more of moderately emetogenic chemotherapeutic agents during Cycle 1
Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2 or Karnofsky score ≥60
Predicted life span ≥4 months
Laboratory values demonstrating adequate hematologic status
Premenopausal females must not be pregnant or lactating and must agree to use effective birth control
Exclusion Criteria:
Received chemotherapy within 6 months prior to starting on study drugs
Scheduled to receive subsequent treatment due to a refractory response to first or second line chemotherapy
Received an investigational drug within 30 days prior to starting on study drugs
Radiation therapy to the abdomen or pelvis in the week prior to starting on study drugs
Vomiting in the 24 hours prior to starting on study drugs
Active infection (e.g., pneumonia) or any uncontrolled disease (e.g., diabetic ketoacidosis, gastrointestinal obstruction) except for malignancy
Known hypersensitivity to Aprepitant (EMEND®), Dexamethasone or 5-HT3 receptor antagonists
Presentation with gastrointestinal obstruction symptoms
Symptomatic primary or metastatic central nervous system malignancy
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
27826874
Citation
Kim JE, Jang JS, Kim JW, Sung YL, Cho CH, Lee MA, Kim DJ, Ahn MJ, Lee KY, Sym SJ, Lim MC, Jung H, Cho EK, Min KW. Efficacy and safety of aprepitant for the prevention of chemotherapy-induced nausea and vomiting during the first cycle of moderately emetogenic chemotherapy in Korean patients with a broad range of tumor types. Support Care Cancer. 2017 Mar;25(3):801-809. doi: 10.1007/s00520-016-3463-0. Epub 2016 Nov 8. Erratum In: Support Care Cancer. 2017 May;25(5):1741.
Results Reference
result
Available IPD and Supporting Information:
Available IPD/Information Type
CSR Synopsis
Available IPD/Information URL
http://www.merck.com/clinical-trials/study.html?id=0869-225&kw=0869-225&tab=access
Learn more about this trial
A Korean Study of Efficacy and Safety of Aprepitant-based Triple Regimen for the Prevention of Chemotherapy-Induced Nausea and Vomiting in the First Cycle of Moderately Emetogenic Chemotherapy (Non-doxorubicin Hydrochloride [Adriamycin] and Cyclophosphamide Regimens) (MK-0869-225) (KMEC)
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