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

Study Overview
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Brief Summary
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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.

Official Title
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EMEND® IV In Salvage Treatment of Chemotherapy-Induced Vomiting

Conditions
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Nausea, Vomiting

Intervention / Treatment
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* Drug: Fosaprepitant dimeglumine
* Drug: 5-HT3 RA
* Drug: Dexamethasone
* Drug: Rescue medication


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fosaprepitant 150 mg<br>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<br>* Fosaprepitant 150 mg, IV on Day 1 of chemotherapy in Cycle 2<br>* Other names: MK-0517, EMEND® IV;Drug: 5-HT3 RA<br>* 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.<br>Drug: Dexamethasone<br>* Dexamethasone will be administered at the same dosage in Cycle 2 of chemotherapy as was used for each particpant in Cycle 1 of chemotherapy.<br>Drug: Rescue medication<br>* 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.<br>|

What is the study measuring?
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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 |