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

Phase 2

Terminated

• Conditions: Vomiting; Nausea
• Interventions: Drug: Fosaprepitant dimeglumine; Drug: 5-HT3 RA; Drug: Dexamethasone; Drug: Rescue medication

• Registration Number: NCT01405924
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-07-28
• Study First Submitted QC: 2011-07-28
• Study First Posted: 2011-07-29
• Study Start: 2011-10-25
• Primary Completion: 2013-12-06
• Study Completion: 2013-12-06
• Results First Submitted: 2014-10-24
• Results First Submitted QC: 2014-10-24
• Results First Posted: 2014-10-29
• Status Verified: 2018-07
• Last Update Submitted: 2018-07-26
• Last Update Posted: 2018-08-27

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Female
• Target Recruitment: 111

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Fosaprepitant 150 mg	Fosaprepitant dimeglumine	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
Fosaprepitant 150 mg	Rescue medication	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
Fosaprepitant 150 mg	5-HT3 RA	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
Fosaprepitant 150 mg	Dexamethasone	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

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With No Vomiting and No Retching During Cycle 2 of Chemotherapy	Up to 120 hours following initiation of chemotherapy in Cycle 2	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.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With No Vomiting and No Retching During Cycle 2 of Chemotherapy Per Type of Chemotherapy	Up to 120 hours following initiation of chemotherapy in Cycle 2	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.
Percentage of Participants With a Complete Response During Cycle 2 of Chemotherapy	Up to 120 hours following initiation of chemotherapy in Cycle 2	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.
Functional Living Index - Emesis (FLIE) Total Score During Cycle 2 of Chemotherapy	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)	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.
Percentage of Participants With No Significant Nausea During Cycle 2 of Chemotherapy	From 24 to 120 hours following initiation of chemotherapy in Cycle 2	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.
Percentage of Participants Who Used No Rescue Medication During Cycle 2 of Chemotherapy	Up to 120 hours following initiation of chemotherapy in Cycle 2	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.