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)

NCT01636947 | Completed Phase 4 Results DMC

• 2 other identifiers: 0869-225MK-0869-225
• Study Type: interventional
• Target: 494
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Nausea; Vomiting

Keywords

chemotherapy; nausea; vomiting; emetogenic; cancer; antiemetics; tumor

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Percentage of Participants With a Complete Response - Overall, Acute, and Delayed Stages

  Hour 0 on Day 1 to Day 5 (approximately 120 hours)

• Number of Emetic Events - Overall Stage

  Hour 0 on Day 1 to Day 5 (approximately 120 hours)

• Percentage of Participants With No Vomiting and No Significant Nausea - Overall Stage

  Days 1 to Day 5

• Percentage of Participants With No Impact on Daily Life - Overall Stage

  Day 6

• Number of Participants With No Use of a Rescue Therapy - Overall, Acute, and Delayed Stages

  Day 1 to Day 5

Study Arms (2)

Aprepitant Regimen

EXPERIMENTAL

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; Drug: Ondansetron; Drug: Dexamethasone; Drug: Ondansetron Placebo; Drug: Rescue Therapy (granisetron, dolasetron, tropisetron or ondansetron; metoclopramide or alizapride).

Control Regimen

ACTIVE COMPARATOR

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; Drug: Ondansetron; Drug: Dexamethasone; Drug: Rescue Therapy (granisetron, dolasetron, tropisetron or ondansetron; metoclopramide or alizapride).

Interventions

Aprepitant DRUG

Aprepitant (125 mg PO, QD) on Day 1, Aprepitant (80 mg PO, QD) on Days 2 and 3

Also known as: MK-0869, EMEND® PO

Aprepitant Regimen

Aprepitant Placebo DRUG

Aprepitant Placebo (PO, QD) on Days 1, 2, and 3

Control Regimen

Ondansetron DRUG

Ondansetron (16 mg, IV, QD) on Day 1 and/or ondansetron (8 mg PO BID) on Days 2 and 3

Also known as: ZOFRAN®

Aprepitant Regimen; Control Regimen

Dexamethasone DRUG

Dexamethasone (20 mg or 12 mg, PO) on Day 1

Also known as: dexamethasone sodium phosphate, dexamethasone acetate, Decadron, Dexasone, Diodex, Hexadrol, Maxidex

Aprepitant Regimen; Control Regimen

Ondansetron Placebo DRUG

Ondansetron Placebo (PO, BID) on Days 2 and 3

Aprepitant Regimen

Rescue Therapy (granisetron, dolasetron, tropisetron or ondansetron; metoclopramide or alizapride). DRUG

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).

Aprepitant Regimen; Control Regimen

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• 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.

  PMID: 27826874 RESULT

MeSH Terms

Conditions

Nausea; Vomiting; Neoplasms

Interventions

Aprepitant; Ondansetron; Dexamethasone; dexamethasone 21-phosphate; dexamethasone acetate; Calcium Dobesilate; Granisetron; dolasetron; Tropisetron; Metoclopramide; alizapride

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Imidazoles; Azoles; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Azabicyclo Compounds; Aza Compounds; Indazoles; Pyrazoles; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring; Benzamides; Amides; para-Aminobenzoates; Aminobenzoates; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Chlorobenzoates; Hydroxybenzoate Ethers; Hydroxybenzoates; Hydroxy Acids; Phenyl Ethers; Phenols

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 5, 2012
• First Posted: July 10, 2012
• Study Start: December 12, 2012
• Primary Completion: August 4, 2014
• Study Completion: August 4, 2014
• Last Updated: September 25, 2018
• Results First Posted: July 30, 2015

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share