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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 3

Conditions: Chemotherapy-Induced Nausea and Vomiting (CINV)

Treatments: Drug: Ondansetron; Drug: Rescue Therapy; Drug: Ondansetron Placebo; Drug: Fosaprepitant dimeglumine; Drug: Dexamethasone; Drug: Dexamethasone Placebo; Drug: Fosaprepitant Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01594749

0517-031

Details and patient eligibility

About

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).

Enrollment: 1,015 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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1,015 participants in 2 patient groups

Fosaprepitant Regimen

Experimental group

Description:

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.

Treatment:

Drug: Dexamethasone Placebo

Drug: Dexamethasone

Drug: Ondansetron Placebo

Drug: Fosaprepitant dimeglumine

Drug: Rescue Therapy

Drug: Ondansetron

Control Regimen

Active Comparator group

Description:

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.

Treatment:

Drug: Dexamethasone

Drug: Rescue Therapy

Drug: Ondansetron

Drug: Fosaprepitant Placebo