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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Vomiting

Intervention / Treatment
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* Drug: aprepitant
* Drug: ondansetron
* Drug: dexamethasone
* Drug: placebo to aprepitant
* Drug: placebo to dexamethasone
* Drug: rescue medication


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 17 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: Aprepitant<br>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<br>* aprepitant capsules<br>Drug: ondansetron<br>* ondansetron IV preparation<br>Drug: dexamethasone<br>* dexamethasone tablets<br>Drug: placebo to dexamethasone<br>* Matching placebo to dexamethasone tablets<br>Drug: rescue medication<br>* 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.<br>|
| Active Comparator: Part 1: Standard Therapy<br>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<br>* ondansetron IV preparation<br>Drug: dexamethasone<br>* dexamethasone tablets<br>Drug: placebo to aprepitant<br>* Matching placebo to aprepitant capsules<br>Drug: rescue medication<br>* 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.<br>|
| Active Comparator: Part 2: Aprepitant<br>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<br>* aprepitant capsules<br>Drug: ondansetron<br>* ondansetron IV preparation<br>Drug: dexamethasone<br>* dexamethasone tablets<br>Drug: placebo to dexamethasone<br>* Matching placebo to dexamethasone tablets<br>Drug: rescue medication<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 |