Efficacy of Aprepitant (Emend®) in Children

Efficacy of Aprepitant (Emend®) in Children Receiving Highly Emetogenic Chemotherapy

The purpose of this study is to find out whether or not adding aprepitant(Emend®) to the standard therapy will help children who receive chemotherapy to have less nausea and vomiting.

Study Overview

• Status: Completed
• Conditions: Nausea; Vomiting; Childhood Cancer
• Intervention / Treatment: Drug: Ondansetron, dexamethasone, aprepitant; Drug: Ondansetron, Dexamethasone, placebo

Detailed Description

1.1 Primary Aim To determine the efficacy of aprepitant (Emend®) in preventing and reducing chemotherapy-induced nausea and vomiting (CINV) when added to standard antiemetic drug regimens for children receiving highly emetogenic chemotherapy. The working hypothesis will be that standard therapy + aprepitant is superior at preventing CINV than standard therapy + placebo.

1.2 Secondary Aim To evaluate the safety and toxicity of aprepitant (Emend®) in children receiving highly emetogenic chemotherapy when compared to standard antiemetic therapy + placebo.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Jimmy Everest Center for Cancer and Blood Disorders in Children

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 20 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

under 20.99 years of age at enrollment

Scheduled to receive two identical cycles of highly emetogenic[1] chemotherapy for treatment of a primary malignancy, including:

Chemotherapy with any one or more of the following single agents in any combination:

• Carboplatin
• Carmustine >250 mg/m2
• Cisplatin
• Cyclophosphamide ≥1 g/m2
• Dactinomycin
• High dose Methotrexate ≥ 5 g/m2

Or any of the following defined combinations:

• Cyclophosphamide + anthracycline
• Cyclophosphamide + etoposide
• Cytarabine 150-200 mg/m2 + daunorubicin
• Cytarabine 300 mg/m2 + etoposide
• Cytarabine 300 mg/m2 + teniposide
• Doxorubicin + ifosfamide
• Doxorubicin + methotrexate 5 g/m2
• Etoposide + ifosfamide

Exclusion Criteria:

• Patients who have received aprepitant in the past.
• Patients who demonstrate evidence of increased intracranial pressure.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ondansetron, dexamethasone, aprepitant; Arm A: Ondansetron 0.15 mg/kg (max 16 mg) IV or PO every 8 hours for at least 3 days, but no longer than 5 days; dexamethasone 0.2mg/kg (max 10 mg) IV or PO daily for at least 3 days, but no longer than 5 days; and aprepitant 3 mg/kg (max 125 mg) PO on day 1, and aprepitant 2 mg/kg (max 80 mg) PO on days 2 and 3 during the first investigational antiemetic cycle. During the next investigational antiemetic cycle, members of this arm will be crossed-over into the placebo arm, where the aprepitant will be replaced by placebo and the dexamethasone dose will be increased to 0.4 mg/kg (max 20 mg) daily.	Drug: Ondansetron, dexamethasone, aprepitant; Ondansetron 0.15 mg/kg (max 16 mg) IV or PO every 8 hours for at least 3 days, but no longer than 5 days; dexamethasone 0.2mg/kg (max 10 mg) IV or PO daily for at least 3 days, but no longer than 5 days; and aprepitant 3 mg/kg (max 125 mg) PO on day 1, and aprepitant 2 mg/kg (max 80 mg) PO on days 2 and 3 during the first investigational antiemetic cycle. During the next investigational antiemetic cycle, members of this arm will be crossed-over into the placebo arm, where the aprepitant will be replaced by placebo and the dexamethasone dose will be increased to 0.4 mg/kg (max 20 mg) daily.; Other Names: ARM A; Aprepitant = Emend
Placebo Comparator: Ondansetron, Dexamethasone, placebo; Arm B: Ondansetron 0.15 mg/kg (max 16 mg) IV or PO every 8 hours for at least 3 days, but no more than 5 days; dexamethasone 0.4 mg/kg (max 20 mg) IV or PO daily for at least 3 days, but no more than 5 days; and a PO placebo for 3 days during the first investigational antiemetic cycle. During the second cycle, members this group will be crossed-over to the experimental arm, where the placebo will be replaced by aprepitant and the dexamethasone will be decreased by 50%.	Drug: Ondansetron, Dexamethasone, placebo; Ondansetron 0.15 mg/kg (max 16 mg) IV or PO every 8 hours for at least 3 days, but no more than 5 days; dexamethasone 0.4 mg/kg (max 20 mg) IV or PO daily for at least 3 days, but no more than 5 days; and a PO placebo for 3 days during the first investigational antiemetic cycle. During the second cycle, members this group will be crossed-over to the experimental arm, where the placebo will be replaced by aprepitant and the dexamethasone will be decreased by 50%.; Other Names: ARM B

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of aprepitant (Emend®) measured through a complete response	• Percentage of study subjects who demonstrate a complete response, defined as no episodes of emesis and no use of rescue medications during the investigational antiemetic cycles.	Up to 11 weeks, or until 3 weeks after the second course of the study regimen
Efficacy of aprepitant (Emend®) measured through episodes of emesis and use of rescue medication.	The total episodes of emesis within 7 days of the first chemotherapy administration of each cycle.; The total number of administrations of rescue medications given for breakthrough nausea or vomiting.	Up to 11 weeks, or until 3 weeks after the second course of the study regimen
Efficacy of aprepitant (Emend®) measured through impact of chemotherapy induced nausea and vomiting on daily life	• A modified, 5-day recall version of the Functional Living Index-Emesis (FLIE) questionnaire	Up to 11 weeks, or until 3 weeks after the second course of the study regimen
Efficacy of aprepitant (Emend®) measured through a pictorial nausea scale	• A modified version of the Baxter Animated Retching Faces (BARF) scale, administered daily.	Up to 11 weeks, or until 3 weeks after the second course of the study regimen

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of aprepitant (Emend®)	Occurrence of adverse events as per the NCI Common Terminology Criteria for Adverse Events (CTCAE) v.4.0. These will be reported spontaneously or on inquiry by the investigator/study nurse, and continuously monitored throughout the trial.; Weekly complete blood count (CBC) for 3 weeks after each investigational antiemetic cycle.; Weekly complete metabolic profile (CMP) for 3 weeks after each investigational antiemetic cycle.	Up to 11 weeks, or until 3 weeks after the second course of the study regimen

Collaborators and Investigators

• Sponsor: University of Oklahoma
• Investigators: Principal Investigator: Rene McNall-Knapp, MD, University of Oklahoma

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2012
• Primary Completion (Actual): June 29, 2017
• Study Completion (Actual): June 29, 2017

Study Registration Dates

• First Submitted: June 18, 2012
• First Submitted That Met QC Criteria: August 8, 2012
• First Posted (Estimate): August 9, 2012

Study Record Updates

• Last Update Posted (Actual): March 23, 2021
• Last Update Submitted That Met QC Criteria: March 18, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Children; Nausea; Vomiting; Aprepitant; Emend®
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Nausea; 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: 0413

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No