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)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01636947
First received: July 5, 2012
Last updated: July 2, 2015
Last verified: July 2015
  Purpose

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.


Condition Intervention Phase
Nausea
Vomiting
Drug: Aprepitant
Drug: Aprepitant Placebo
Drug: Ondansetron
Drug: Dexamethasone
Drug: Ondansetron Placebo
Drug: Rescue Therapy (granisetron, dolasetron, tropisetron or ondansetron; metoclopramide or alizapride).
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • The Percentage of Participants With No Vomiting - Overall Stage [ Time Frame: Hour 0 on Day 1 to Day 5 (approximately 120 hours) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Hour 0 on Day 1 to Day 5 (approximately 120 hours) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Hour 0 on Day 1 to Day 5 (approximately 120 hours) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Days 1 to Day 5 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 6 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 to Day 5 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 through Day 29 (Up to 28 days after first dose of study drug) ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Day 1, Day 2 to Day 5 ] [ Designated as safety issue: No ]
    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.


Enrollment: 494
Study Start Date: December 2012
Study Completion Date: August 2014
Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: ZOFRAN®
Drug: Dexamethasone
Dexamethasone (20 mg or 12 mg, PO) on Day 1
Other Names:
  • dexamethasone sodium phosphate
  • dexamethasone acetate
  • Decadron
  • Dexasone
  • Diodex
  • Hexadrol
  • Maxidex
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: Aprepitant Placebo
Aprepitant Placebo (PO, QD) on Days 1, 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 Name: ZOFRAN®
Drug: Dexamethasone
Dexamethasone (20 mg or 12 mg, PO) on Day 1
Other Names:
  • dexamethasone sodium phosphate
  • dexamethasone acetate
  • Decadron
  • Dexasone
  • Diodex
  • Hexadrol
  • Maxidex
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).

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01636947

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01636947     History of Changes
Other Study ID Numbers: 0869-225, MK-0869-225
Study First Received: July 5, 2012
Results First Received: July 2, 2015
Last Updated: July 2, 2015
Health Authority: South Korea: Korea Food and Drug Administration (KFDA)

Keywords provided by Merck Sharp & Dohme Corp.:
chemotherapy
nausea
vomiting
emetogenic
cancer
antiemetics
tumor

Additional relevant MeSH terms:
Nausea
Vomiting
Signs and Symptoms
Signs and Symptoms, Digestive
Alizapride
Aprepitant
BB 1101
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Dolasetron
Emetics
Fosaprepitant
Granisetron
Metoclopramide
Ondansetron
Tropisetron
Anti-Anxiety Agents
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Antipruritics
Antipsychotic Agents
Autonomic Agents
Central Nervous System Agents
Central Nervous System Depressants
Dermatologic Agents
Dopamine Agents
Dopamine Antagonists

ClinicalTrials.gov processed this record on August 02, 2015