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) (KMEC)

August 27, 2018 updated by: Merck Sharp & Dohme LLC

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)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

494

Phase

  • Phase 4

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Aprepitant Regimen
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.
Drug: Aprepitant
Aprepitant (125 mg PO, QD) on Day 1, Aprepitant (80 mg PO, QD) on Days 2 and 3
Other Names:
  • MK-0869
  • EMEND® PO
Drug: Ondansetron
Ondansetron (16 mg, IV, QD) on Day 1 and/or ondansetron (8 mg PO BID) on Days 2 and 3
Other Names:
  • ZOFRAN®
Drug: Dexamethasone
Dexamethasone (20 mg or 12 mg, PO) on Day 1
Other Names:
  • Decadron
  • Hexadrol
  • Dexasone
  • Maxidex
  • Diodex
  • dexamethasone sodium phosphate
  • dexamethasone acetate
Drug: Ondansetron Placebo
Ondansetron Placebo (PO, BID) on Days 2 and 3
Drug: Rescue Therapy (granisetron, dolasetron, tropisetron or ondansetron; metoclopramide or alizapride).
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).
Active Comparator: Control Regimen
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.
Drug: Ondansetron
Ondansetron (16 mg, IV, QD) on Day 1 and/or ondansetron (8 mg PO BID) on Days 2 and 3
Other Names:
  • ZOFRAN®
Drug: Dexamethasone
Dexamethasone (20 mg or 12 mg, PO) on Day 1
Other Names:
  • Decadron
  • Hexadrol
  • Dexasone
  • Maxidex
  • Diodex
  • dexamethasone sodium phosphate
  • dexamethasone acetate
Drug: Rescue Therapy (granisetron, dolasetron, tropisetron or ondansetron; metoclopramide or alizapride).
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).
Drug: Aprepitant Placebo
Aprepitant Placebo (PO, QD) on Days 1, 2, and 3

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Percentage of Participants With No Vomiting - Overall Stage
Time Frame: Hour 0 on Day 1 to Day 5 (approximately 120 hours)
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).
Hour 0 on Day 1 to Day 5 (approximately 120 hours)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With a Complete Response - Overall, Acute, and Delayed Stages
Time Frame: Hour 0 on Day 1 to Day 5 (approximately 120 hours)
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.
Hour 0 on Day 1 to Day 5 (approximately 120 hours)
Number of Emetic Events - Overall Stage
Time Frame: Hour 0 on Day 1 to Day 5 (approximately 120 hours)
The number of emetic events that occurred during the Overall Stage (0 to 120 hours after initiation of MEC) are presented.
Hour 0 on Day 1 to Day 5 (approximately 120 hours)
Percentage of Participants With No Vomiting and No Significant Nausea - Overall Stage
Time Frame: Days 1 to Day 5
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.
Days 1 to Day 5
Percentage of Participants With No Impact on Daily Life - Overall Stage
Time Frame: Day 6
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.
Day 6
Number of Participants With No Use of a Rescue Therapy - Overall, Acute, and Delayed Stages
Time Frame: Day 1 to Day 5
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.
Day 1 to Day 5
Percentage of Participants With One or More Clinical Adverse Event
Time Frame: Day 1 through Day 29 (Up to 28 days after first dose of study drug)
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.
Day 1 through Day 29 (Up to 28 days after first dose of study drug)
Percentage of Participants With No Vomiting - Acute and Delayed Stages
Time Frame: Day 1, Day 2 to Day 5
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.
Day 1, Day 2 to Day 5

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Merck Sharp & Dohme LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 12, 2012

Primary Completion (Actual)

August 4, 2014

Study Completion (Actual)

August 4, 2014

Study Registration Dates

First Submitted

July 5, 2012

First Submitted That Met QC Criteria

July 9, 2012

First Posted (Estimate)

July 10, 2012

Study Record Updates

Last Update Posted (Actual)

September 25, 2018

Last Update Submitted That Met QC Criteria

August 27, 2018

Last Verified

August 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0869-225
  • MK-0869-225 (Other Identifier: Merck protocol number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Study Data/Documents

  1. CSR Synopsis

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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