Efficacy and Safety of Fosaprepitant Dimeglumine in Preventing Chemotherapy-Induced Nausea and Vomiting (MK-0517-031)

Study Overview
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Brief Summary
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This study aims to demonstrate that, when given concomitantly with a 5-hydroxytryptamine 3 (5-HT3) antagonist and a corticosteroid, a single 150 mg intravenous (IV) dose of fosaprepitant given on Day 1 is superior to the control regimen of 5-HT3 antagonist and corticosteroid only, in preventing chemotherapy-induced nausea and vomiting (CINV) associated with moderately emetogenic chemotherapy (MEC).

Official Title
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A Phase III, Randomized, Double-Blind, Active Comparator-Controlled Parallel-Group Study, Conducted Under In-House Blinding Conditions, to Examine the Efficacy and Safety of a Single 150 mg Dose of Intravenous Fosaprepitant Dimeglumine for the Prevention of Chemotherapy-Induced Nausea and Vomiting (CINV) Associated With Moderately Emetogenic Chemotherapy

Conditions
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Chemotherapy-Induced Nausea and Vomiting (CINV)

Intervention / Treatment
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* Drug: Fosaprepitant dimeglumine
* Drug: Fosaprepitant Placebo
* Drug: Dexamethasone
* Drug: Ondansetron
* Drug: Dexamethasone Placebo
* Drug: Ondansetron Placebo
* Drug: Rescue Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has a histologically or cytologically confirmed malignant disease Is naive to moderately and highly emetogenic chemotherapy Is scheduled to receive a single IV dose of one or more MEC agents on Day 1, except for the combination of anthracycline and cyclophosphamide Has a predicted life expectancy of at least 4 months, and a Karnofsky score of at least 60 indicating that the participant requires occasional assistance, but is able to care for most of his/her needs. Female of childbearing potential demonstrates a negative urine pregnancy test, and agrees to remain abstinent or use two acceptable forms of birth control for at least 14 days prior to study, throughout the study, and at least 1 month following last dose of study drug. Exclusion Criteria: Has vomited in the 24 hours prior to treatment Day 1 Has symptomatic primary or metastatic symptomatic central nervous system malignancy causing nausea and/or vomiting Is scheduled to receive chemotherapy agent classified as highly emetogenic Has received or will receive total body irradiation, or radiation therapy to the abdomen, pelvis, head and neck in the week prior to Treatment Days 1 through Day 6 of the Treatment Period Has illness or history of illness which might confound study results or pose unwarranted risk Known history of QT interval prolongation Uses illicit drugs or abuses alcohol Mentally incapacitated or has a significant emotional or psychiatric disorder History of hypersensitivity to aprepitant, ondansetron or dexamethasone Pregnant or breast-feeding Has participated in a study with aprepitant or taken a non-approved (investigational) drug within the last 4 weeks Has concurrent condition, such as systemic fungal infection or uncontrolled diabetes, that precludes administration of dexamethasone.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fosaprepitant Regimen<br>On Day 1, participants received fosaprepitant, 150 mg intravenous (IV) infusion,  30 minutes prior to chemotherapy PLUS dexamethasone 12 mg, orally (PO)  30 minutes prior to chemotherapy PLUS ondansetron 16 mg total dose: 8 mg PO  30-60 minutes prior to chemotherapy, followed by 8 mg PO, 8 hours after first dose PLUS dexamethasone placebo, PO  30 minutes prior to chemotherapy. On Days 2 and 3, participants received ondansetron placebo, PO every 12 hours. Rescue Therapy: For established cases of nausea or vomiting, medications may have been prescribed from these permitted choices: 5-HT3 antagonists (granisetron, dolasetron, tropisetron or ondansetron); phenothiazines (e.g. prochlorperazine, fluphenazine, perphenazine, thiethylperazine, or chlorpromazine); butyrophenones (e.g. haloperidol or droperidol); benzamides (e.g. metoclopramide or alizapride); benzodiazepines; corticosteroids; domperidone. | Drug: Fosaprepitant dimeglumine<br> <br> * Other names: MK-0517;Drug: Dexamethasone<br> <br> * Other names: Decadron;Drug: Ondansetron<br> <br> * Other names: Zofran;Drug: Dexamethasone Placebo<br> <br> Drug: Ondansetron Placebo<br> <br> Drug: Rescue Therapy<br> <br> |
| Active Comparator: Control Regimen<br>On Day 1, participants received fosaprepitant placebo, 150 mL IV infusion,  30 minutes prior to chemotherapy PLUS dexamethasone 20 mg, PO  30 minutes prior to chemotherapy PLUS ondansetron 16 mg total dose: 8 mg PO  30-60 minutes prior to chemotherapy; followed by 8 mg PO, 8 hours after the first dose. On Days 2-3, participants received ondansetron 8 mg, PO every 12 hours. Rescue Therapy: For established cases of nausea or vomiting, medications may have been prescribed from these permitted choices: 5-HT3 antagonists (granisetron, dolasetron, tropisetron or ondansetron); phenothiazines (e.g. prochlorperazine, fluphenazine, perphenazine, thiethylperazine, or chlorpromazine); butyrophenones (e.g. haloperidol or droperidol); benzamides (e.g. metoclopramide or alizapride); benzodiazepines; corticosteroids; domperidone. | Drug: Fosaprepitant Placebo<br> <br> Drug: Dexamethasone<br> <br> * Other names: Decadron;Drug: Ondansetron<br> <br> * Other names: Zofran;Drug: Rescue Therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Complete Response From 25 to 120 Hours After Initiation of Moderately Emetogenic Chemotherapy (MEC) | A Complete Response was defined as no vomiting and no use of rescue medication. | 25 to 120 hours after initiation of MEC | 
| Percentage of Participants With Infusion-site Thrombophlebitis | The percentages of participants with infusion-site thrombophlebitis are presented. Thrombophlebitis was defined as a condition affecting a superficial vein used for an IV infusion, associated with red color, hardness upon palpation, and the presence of a tender cord and possible fever. | Day 1 through Day 17, inclusive | 
| Percentage of Participants With Severe Infusion-site Reactions | The percentages of participants with severe infusion-site reactions, including severe site pain, or severe site redness (erythema) or severe site hardness (induration) are presented. | Day 1 through Day 17, inclusive | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Complete Response From 0 to 120 Hours After Initiation of MEC | A Complete Response was defined as no vomiting and no use of rescue medication. | 0 to 120 hours after initiation of MEC | 
| Percentage of Participants With Complete Response From 0 to 24 Hours After Initiation of MEC | A Complete Response was defined as no vomiting and no use of rescue medication. | 0 to 24 hours after initiation of MEC | 
| Percentage of Participants With No Vomiting From 0 to 120 Hours After Initiation of MEC | No Vomiting was defined as no emetic (vomiting) episodes, including no vomiting and no retching or dry heaves (attempts to vomit that are not productive of stomach contents), regardless of use of rescue medication. | 0 to 120 hours after initiation of MEC | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NK-1 Receptor Antagonist, CINV, Emesis, MEC