Study of Aprepitant (MK-0869) for Chemotherapy-Induced Nausea and Vomiting (CINV) in Adolescent Participants (MK-0869-097)

A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study, Conducted Under In-House Blinding Conditions, to Examine the Safety, Tolerability, and Efficacy of Aprepitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting Associated With Emetogenic Chemotherapy in Adolescent Patients

This study is being conducted to demonstrate that aprepitant (MK-0869) prevents nausea and vomiting caused by emetogenic cancer chemotherapy in adolescent participants. Participants treated with emetogenic cancer chemotherapies that include either cisplatin, cyclophosphamide, or carboplatin, or participants who experienced nausea and/or vomiting when treated with a previously administered chemotherapy regimen that is planned to be repeated will be enrolled in this study. In the double-blind Part 1 of this study, enrolled participants will be randomized to receive either aprepitant or standard therapy. In Part 2 of this study, enrolled participants will receive open-label aprepitant.

Study Overview

• Status: Completed
• Conditions: Vomiting
• Intervention / Treatment: Drug: aprepitant; Drug: ondansetron; Drug: dexamethasone; Drug: placebo to dexamethasone; Drug: rescue medication; Drug: placebo to aprepitant

Detailed Description

The duration of treatment is the first 4 days of one 28-day cycle (Cycle 1). Participants who successfully complete Cycle 1 may be eligible to participate for 9 subsequent optional, open-label, 28-day cycles.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Cycle 1: Participant is to be treated with an emetogenic chemotherapy regimen that includes either cisplatin, cyclophosphamide, or carboplatin, for a documented malignancy. OR Participant did not tolerate a previously administered chemotherapy regimen, for a documented malignancy, secondary to nausea and/or vomiting that is planned to be repeated.
• Cycle 1: Participant has Karnofsky score ≥60
• Cycle 1: Participant has a predicted life expectancy of ≥3 months

Exclusion Criteria:

• Cycle 1: Participant will receive stem cell rescue therapy in conjunction with course of chemotherapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Aprepitant; Day 1: aprepitant 125 mg orally (PO), ondansetron 0.15 mg/kg x 3 doses intravenously (IV), dexamethasone 8 mg PO. Day 2: aprepitant 80 mg PO, ondansetron 0.15 mg/kg x 3 doses IV, dexamethasone 4 mg PO. Day 3: aprepitant 80 mg PO, dexamethasone 4 mg PO. Day 4: dexamethasone 4 mg PO. For 1 cycle and up to 9 subsequent optional cycles.	Drug: aprepitant; aprepitant capsules; Drug: ondansetron; ondansetron IV preparation; Drug: dexamethasone; dexamethasone tablets; Drug: placebo to dexamethasone; Matching placebo to dexamethasone tablets; Drug: rescue medication; Participants are allowed to take rescue medication throughout for nausea or vomiting. At the discretion of the investigator, participants are provided with a prescription for rescue medications. Recommended rescue medications are: 5-HT3 antagonists, phenothiazines, butyrophenones, benzamides, corticosteroids, benzodiazepines, domperidone, H1-receptor antagonist, and piperazine derivatives.
Active Comparator: Part 1: Standard Therapy; Day 1: placebo to aprepitant 125 mg PO, ondansetron 0.15 mg/kg x 3 doses IV, dexamethasone 16 mg PO. Day 2: placebo to aprepitant 80 mg PO, ondansetron 0.15 mg/kg x 3 doses IV, dexamethasone 8 mg PO. Day 3: placebo for aprepitant 80 mg PO, dexamethasone 8 mg PO. Day 4: dexamethasone 8 mg PO. For 1 cycle; participants may receive open-label aprepitant for up to 9 subsequent optional cycles.	Drug: ondansetron; ondansetron IV preparation; Drug: dexamethasone; dexamethasone tablets; Drug: rescue medication; Participants are allowed to take rescue medication throughout for nausea or vomiting. At the discretion of the investigator, participants are provided with a prescription for rescue medications. Recommended rescue medications are: 5-HT3 antagonists, phenothiazines, butyrophenones, benzamides, corticosteroids, benzodiazepines, domperidone, H1-receptor antagonist, and piperazine derivatives.; Drug: placebo to aprepitant; Matching placebo to aprepitant capsules
Active Comparator: Part 2: Aprepitant; Day 1: aprepitant 125 mg PO, ondansetron 0.15 mg/kg x 3 doses IV, dexamethasone 8 mg PO. Day 2: aprepitant 80 mg PO, ondansetron 0.15 mg/kg x 3 doses IV, dexamethasone 4 mg PO. Day 3: aprepitant 80 mg PO, dexamethasone 4 mg PO. Day 4: dexamethasone 4 mg PO. For up to 10 cycles.	Drug: aprepitant; aprepitant capsules; Drug: ondansetron; ondansetron IV preparation; Drug: dexamethasone; dexamethasone tablets; Drug: placebo to dexamethasone; Matching placebo to dexamethasone tablets; Drug: rescue medication; Participants are allowed to take rescue medication throughout for nausea or vomiting. At the discretion of the investigator, participants are provided with a prescription for rescue medications. Recommended rescue medications are: 5-HT3 antagonists, phenothiazines, butyrophenones, benzamides, corticosteroids, benzodiazepines, domperidone, H1-receptor antagonist, and piperazine derivatives.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants Who Experience Study-drug-related Adverse Events (Cycle 1)	Up to 14 days after last dose of anti-emetic therapy in Cycle 1 (Up to 18 days)

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants Who Experience a Complete Response (CR) to Anti-emetic Therapy (Cycle 1)	Up to 120 hours after initiation of emetogenic chemotherapy in Cycle 1
Percentage of Participants Who Experience Absence of Nausea (Cycle 1)	Up to 120 hours after initiation of emetogenic chemotherapy in Cycle 1
Percentage of Participants Who Experience Absence of Vomiting (Cycle 1)	Up to 120 hours after initiation of emetogenic chemotherapy in Cycle 1
Percentage of Participants Who Experience Serious Adverse Events (Cycles 2-10)	Up to 14 days after last dose of anti-emetic therapy in Cycles 2-10 (Up to 10.5 months)
Percentage of Participants Who Experience Study-drug-related Adverse Events (Cycles 2-10)	Up to 14 days after last dose of anti-emetic therapy in Cycles 2-10 (Up to 10.5 months)
Percentage of Participants Who Discontinue Study Due to Study-drug-related Adverse Events (Cycles 2-10)	Up to Day 4 of Cycles 2-10 (Up to 10 months)
Percentage of Participants Who Experience Serious Adverse Events (Cycle 1)	Up to 14 days after last dose of anti-emetic therapy in Cycle 1 (Up to 18 days)
Percentage of Participants Who Experience Serious Study-drug-related Adverse Events (Cycle 1)	Up to 14 days after last dose of anti-emetic therapy in Cycle 1 (Up to 18 days)
Percentage of Participants Who Discontinue Study Due to Study-drug-related Adverse Events (Cycle 1)	Up to Day 4 of Cycle 1
Aprepitant Plasma Drug Concentration Profiles and Pharmacokinetics	Up to 24 hours after first dose of aprepitant

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Gore L, Chawla S, Petrilli A, Hemenway M, Schissel D, Chua V, Carides AD, Taylor A, Devandry S, Valentine J, Evans JK, Oxenius B; Adolescent Aprepitant in Cancer Study Group. Aprepitant in adolescent patients for prevention of chemotherapy-induced nausea and vomiting: a randomized, double-blind, placebo-controlled study of efficacy and tolerability. Pediatr Blood Cancer. 2009 Feb;52(2):242-7. doi: 10.1002/pbc.21811.

Study record dates

Study Major Dates

• Study Start: April 1, 2004
• Primary Completion (Actual): September 1, 2006
• Study Completion (Actual): March 1, 2007

Study Registration Dates

• First Submitted: March 31, 2004
• First Submitted That Met QC Criteria: April 1, 2004
• First Posted (Estimate): April 2, 2004

Study Record Updates

• Last Update Posted (Estimate): August 5, 2014
• Last Update Submitted That Met QC Criteria: August 4, 2014
• Last Verified: August 1, 2014

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; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protease Inhibitors; Dermatologic Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Serotonin Antagonists; Anti-Anxiety Agents; Antipruritics; Neurokinin-1 Receptor Antagonists; Dexamethasone; Dexamethasone acetate; BB 1101; Ondansetron; Aprepitant; Fosaprepitant
• Other Study ID Numbers: 0869-097; Formerly-0304AHEC; MK-0869-097 (Other Identifier: Merck Protocol Number); 2004_099 (Other Identifier: Telerx Protocol Number)