Fosaprepitant (MK-0517, EMEND® IV) In Salvage Treatment of Chemotherapy-Induced Vomiting (MK-0517-030) (EVADE)

EMEND® IV In Salvage Treatment of Chemotherapy-Induced Vomiting

This study will assess the efficacy of a single dose of intravenous (IV) fosaprepitant (MK-0517, EMEND® IV) as salvage therapy when added to a 5-hydroxytryptamine receptor 3 antagonist (5-HT3 RA) and dexamethasone for the prevention of chemotherapy-induced vomiting (CIV) in participants who experienced CIV in the first cycle of moderately emetic chemotherapy (MEC). The primary hypothesis is that there will be no vomiting and no retching in at least 20% of participants during the second cycle of MEC in participants who previously experienced vomiting during the first cycle of MEC.

Study Overview

• Status: Terminated
• Conditions: Nausea; Vomiting
• Intervention / Treatment: Drug: Fosaprepitant dimeglumine; Drug: 5-HT3 RA; Drug: Dexamethasone; Drug: Rescue medication

• Study Type: Interventional
• Enrollment (Actual): 111
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Diagnosed with either breast or gynecological cancer
• Receiving either AC-like or CT MEC
• Experienced at least 1 episode of vomiting or retching during the first 5 days following Cycle 1 of chemotherapy that was thought to be due to chemotherapy. Received standard chemotherapy-induced nausea and vomiting (CINV) prophylaxis not containing aprepitant or fosaprepitant
• No change in chemotherapy at Cycle 2
• No change in Cycle 1 antiemetic regimen at Cycle 2
• Eastern Cooperative Oncology Group (ECOG) status 0-1

Exclusion Criteria:

• Requires increase in systemic corticosteroid therapy
• Used benzodiazepines or opiates in the 48 hours prior to Cycle 2 chemotherapy
• Received or will receive radiation therapy to the abdomen or pelvis in the week prior to Visit 1 or in Days 1-6 following chemotherapy
• Vomited in the 24 hours prior to Treatment Day 1
• Pregnant or breast-feeding
• Participating in a study with aprepitant or fosaprepitant or has taken an investigational drug in the last 4 weeks
• Symptomatic central nervous system metastasis
• History of other malignancies in the last 2 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Fosaprepitant 150 mg; Women with breast cancer receiving anthracycline-cyclophosphamide (AC)-like chemotherapy and women with gynecological cancer receiving carboplatin-paclitaxel (CT) chemotherapy receive fosaprepitant 150 mg administered intravenously (IV) on Day 1 of Cycle 2 of chemotherapy

Drug: Fosaprepitant dimeglumine; Fosaprepitant 150 mg, IV on Day 1 of chemotherapy in Cycle 2; Other Names: MK-0517, EMEND® IV; Drug: 5-HT3 RA; 5-HT3 RA will be administered at the same dosage in Cycle 2 of chemotherapy as was used for each particpant in Cycle 1 of chemotherapy.; Drug: Dexamethasone; Dexamethasone will be administered at the same dosage in Cycle 2 of chemotherapy as was used for each particpant in Cycle 1 of chemotherapy.; Drug: Rescue medication; Rescue medication is defined as any medication used to relieve the symptoms of established nausea or vomiting. Multiple medications are permitted by the protocol and may be taken by the participant, including 5-HT3 antagonists, phenothiazines and benzodiazepines.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With No Vomiting and No Retching During Cycle 2 of Chemotherapy	A vomiting episode is defined as one or more episodes of emesis (expulsion of stomach contents through the mouth) or retching (an attempt to vomit that is not productive of stomach contents). Distinct vomiting episodes are separated by the absence of emesis and retching for at least one minute. The date and time of each vomiting episode was recorded by participants in diaries at the time of occurrence. The percentage of partcipants with no vomiting and no retching episodes 0-120 hours following chemotherapy in Cycle 2 was calculated.	Up to 120 hours following initiation of chemotherapy in Cycle 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With No Vomiting and No Retching During Cycle 2 of Chemotherapy Per Type of Chemotherapy	A vomiting episode is defined as one or more episodes of emesis (expulsion of stomach contents through the mouth) or retching (an attempt to vomit that is not productive of stomach contents). Distinct vomiting episodes are separated by the absence of emesis and retching for at least one minute. The date and time of each vomiting episode was recorded by participants in diaries at the time of occurrence. The percentage of partcipants with no vomiting and no retching episodes 0-120 hours following initiation of chemotherapy in Cycle 2 was calculated based on type of chemotherapy received.	Up to 120 hours following initiation of chemotherapy in Cycle 2
Percentage of Participants With a Complete Response During Cycle 2 of Chemotherapy	A complete response is defined as no vomiting/no retching episodes and no use of rescue medication during the 120 hours following initiation of chemotherapy. The percentage of participants with a complete response during Cycle 2 of chemotherapy was calculated.	Up to 120 hours following initiation of chemotherapy in Cycle 2
Functional Living Index - Emesis (FLIE) Total Score During Cycle 2 of Chemotherapy	The FLIE Total Score is an 18-question quality-of-life questionnaire on the impact of nausea and vomiting (9 questions on nausea and 9 questions on vomiting) on daily life. Each question uses a visual analog scale (VAS) to rate the impact of nausea/vomiting from 1 to 7. FLIE Total Scores are calculated by summing the responses to the 18 questions and can range from 18-126 (18=a great deal of impairment, 126=no impairment), with a higher score indicating less impairment due to nausea and vomiting. "No Impact" on daily life was defined as a FLIE Total Score >108. Participants completed the FLIE questionnaire on the morning of Day 6 following initiation of chemotherapy in Cycle 2; their responses covered their experiences with nausea and vomiting over the previous 5 days.	From Day 1 (prior to initiation of chemotherapy in Cycle 2) to morning of Day 6 (up to ~120 hours following initiation of chemotherapy in Cycle 2)
Percentage of Participants With No Significant Nausea During Cycle 2 of Chemotherapy	Participants rated their degree of nausea in response to "How much nausea have you had over the last 24 hours?" using a 100-mm visual analog scale (VAS, 0=no nausea, 100=nausea as bad as it could be) on Days 2-6 following initiation of chemotherapy. No significant nausea was defined as VAS score <25 mm over the 24-120 hours following initiation of chemotherapy. The percentage of participants who experienced no significant nausea during Cycle 2 of chemotherapy was calculated.	From 24 to 120 hours following initiation of chemotherapy in Cycle 2
Percentage of Participants Who Used No Rescue Medication During Cycle 2 of Chemotherapy	Participants recorded any use of rescue medication for established nausea/vomiting in their daily diaries from initiation of chemotherapy infusion through the morning of Day 6. The percentage of participants who used no rescue medication during Cycle 2 of chemotherapy was calculated.	Up to 120 hours following initiation of chemotherapy in Cycle 2

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): October 25, 2011
• Primary Completion (Actual): December 6, 2013
• Study Completion (Actual): December 6, 2013

Study Registration Dates

• First Submitted: July 28, 2011
• First Submitted That Met QC Criteria: July 28, 2011
• First Posted (Estimate): July 29, 2011

Study Record Updates

• Last Update Posted (Actual): August 27, 2018
• Last Update Submitted That Met QC Criteria: July 26, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Vomiting; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neurokinin-1 Receptor Antagonists; Dexamethasone; Aprepitant; Fosaprepitant
• Other Study ID Numbers: 0517-030

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