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)

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Nausea, Vomiting

Intervention / Treatment
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* Drug: Aprepitant
* Drug: Aprepitant Placebo
* Drug: Ondansetron
* Drug: Dexamethasone
* Drug: Ondansetron Placebo
* Drug: Rescue Therapy (granisetron, dolasetron, tropisetron or ondansetron; metoclopramide or alizapride).


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aprepitant Regimen<br>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<br>* Aprepitant (125 mg PO, QD) on Day 1, Aprepitant (80 mg PO, QD) on Days 2 and 3<br>* Other names: EMEND® PO;Drug: Ondansetron<br>* Ondansetron (16 mg, IV, QD) on Day 1 and/or ondansetron (8 mg PO BID) on Days 2 and 3<br>* Other names: ZOFRAN®;Drug: Dexamethasone<br>* Dexamethasone (20 mg or 12 mg, PO) on Day 1<br>* Other names: Maxidex;Drug: Ondansetron Placebo<br>* Ondansetron Placebo (PO, BID) on Days 2 and 3<br>Drug: Rescue Therapy (granisetron, dolasetron, tropisetron or ondansetron; metoclopramide or alizapride).<br>* 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).<br>|
| Active Comparator: Control Regimen<br>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: Aprepitant Placebo<br>* Aprepitant Placebo (PO, QD) on Days 1, 2, and 3<br>Drug: Ondansetron<br>* Ondansetron (16 mg, IV, QD) on Day 1 and/or ondansetron (8 mg PO BID) on Days 2 and 3<br>* Other names: ZOFRAN®;Drug: Dexamethasone<br>* Dexamethasone (20 mg or 12 mg, PO) on Day 1<br>* Other names: Maxidex;Drug: Rescue Therapy (granisetron, dolasetron, tropisetron or ondansetron; metoclopramide or alizapride).<br>* 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).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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emetogenic, antiemetics, tumor, chemotherapy, nausea, vomiting, cancer