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A Study of the Safety and Efficacy of Aprepitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting (CINV) in Pediatric Participants (MK-0869-208)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01362530
First received: May 26, 2011
Last updated: August 25, 2014
Last verified: August 2014
  Purpose

This study will compare the safety and efficacy of a three-day oral aprepitant regimen (aprepitant plus ondansetron) to ondansetron alone in the prevention of chemotherapy-induced nausea and vomiting (CINV) in the 120 hours following the initiation of chemotherapy in pediatric participants. Those who complete this first cycle of treatment and meet certain eligibility criteria will have the option of continuing for 5 additional cycles of open-label aprepitant.


Condition Intervention Phase
Chemotherapy Induced Nausea and Vomiting
Drug: Aprepitant 125 mg
Drug: Aprepitant 80 mg
Drug: Aprepitant powder for suspension (PFS)
Drug: Ondansetron
Drug: Placebo for Aprepitant 125 mg
Drug: Placebo for Aprepitant 80 mg
Drug: Placebo for Aprepitant PFS
Drug: Emetogenic chemotherapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
Official Title: A Phase III, Randomized, Double-Blind, Active Comparator-Controlled Clinical Trial, Conducted Under In-House Blinding Conditions, to Examine the Efficacy and Safety of Aprepitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting (CINV) in Pediatric Patients

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Percentage of Participants With a Complete Response in the Delayed Phase of Cycle 1 [ Time Frame: 25 to 120 hours after the start of chemotherapy ] [ Designated as safety issue: No ]
    Delayed Phase was defined as 25-120 hours after the start of chemotherapy. Complete response was defined as no vomiting or retching and no use of rescue medication in the delayed phase of Cycle 1.


Secondary Outcome Measures:
  • Percentage of Participants With a Complete Response in the Acute Phase of Cycle 1 [ Time Frame: 0 to 24 hours after initiation of chemotherapy ] [ Designated as safety issue: No ]
    Acute phase was defined as 0 to 24 hours after the start of chemotherapy. Complete response was defined as no vomiting or retching and no use of rescue medication in the acute phase of Cycle 1.

  • Percentage of Participants With a Complete Response in the Overall Phase of Cycle 1 [ Time Frame: 0 to 120 hours after initiation of chemotherapy ] [ Designated as safety issue: No ]
    Overall phase was defined as 0 to 120 hourse after the start of chemotherapy. Complete response was defined as no vomiting or retching and no use of rescue medication in the overall phase of Cycle 1.

  • Percentage of Participants With No Vomiting in the Overall Phase of Cycle 1 [ Time Frame: 0 to 120 hours after initiation of chemotherapy ] [ Designated as safety issue: No ]
    Overall phase was defined as 0 to 120 hourse after the start of chemotherapy. No vomiting was defined as no emesis or retching or dry heaves in the overall phase of Cycle 1.


Enrollment: 307
Study Start Date: September 2011
Study Completion Date: August 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Aprepitant Regimen

Cycle 1:

Participants 12 to 17 years of age, Day 1: aprepitant 125 mg capsule orally (PO) + ondansetron, Days 2 to 3: aprepitant 80 mg capsule PO. Participants 6 months to <12 years of age, Day 1: aprepitant powder for suspension (PFS), 3.0 mg/kg (up to 125 mg) + ondansetron, Days 2 to 3: aprepitant PFS, 2.0 mg/kg (up to 80 mg).

Optional Cycles 2-6:

Open-label aprepitant administered in the same manner as in Cycle 1.

Drug: Aprepitant 125 mg
On the morning of Day 1: one 125 mg capsule PO 60 minutes prior to chemotherapy for participants 12 to 17 years of age
Other Name: MK-0869, Emend®
Drug: Aprepitant 80 mg
On the morning of Days 2 and 3: one 80 mg capsule PO for participants 12 to 17 years of age
Other Name: MK-0869, Emend®
Drug: Aprepitant powder for suspension (PFS)
On the morning of Day 1: 3.0 mg/kg (up to 125 mg) PO 60 minutes prior to chemotherapy for participants 6 months to <12 years of age. On the morning of Days 2 and 3: 2.0 mg/kg (up to 80 mg) PO 60 minutes prior to chemotherapy (if applicable) for participants 6 months to <12 years of age
Other Name: MK-0869, Emend®
Drug: Ondansetron
Day 1: Administered according to product label for pediatric usage or local standard of care
Other Name: Zofran™
Drug: Emetogenic chemotherapy
Any moderately or highly emetic chemotherapeutic agent such as cyclophosphamide, doxorubicin, methotrexate, carboplatin, cisplatin, irinotecan, carmustine, ifosfamide, and streptozocin, or chemotherapeutics of a lower emetogenicity that were not previously tolerated. No chemotherapeutic agents were specified by the protocol, and many could potentially have been used."
Placebo Comparator: Control Regimen
Cycle 1: Participants 12 to 17 years of age, Day 1: matching placebo for aprepitant 125 mg capsule oral (PO) + ondansetron Days 2 to 3: matching placebo for aprepitant 80 mg capsule PO. Participants 6 months to <12 years of age, Day 1: matching placebo PFS: 3.0 mg/kg (up to 125 mg) + ondansetron, Days 2 to 3: matching placebo PFS: 2.0 mg/kg (up to 80 mg). Optional Cycles 2-6: Open-label aprepitant administered in the same manner as in Cycle 1.
Drug: Ondansetron
Day 1: Administered according to product label for pediatric usage or local standard of care
Other Name: Zofran™
Drug: Placebo for Aprepitant 125 mg
On the morning of Day 1: one 125 mg capsule PO 60 minutes prior to chemotherapy for participants 12 to 17 years of age
Drug: Placebo for Aprepitant 80 mg
On the morning of Days 2 and 3: one 80 mg capsule PO for participants 12 to 17 years of age
Drug: Placebo for Aprepitant PFS
On the morning of Day 1: 3.0 mg/kg (up to 125 mg) PO 60 minutes prior to chemotherapy for participants 6 months to <12 years of age. On the morning of Days 2 and 3: 2.0 mg/kg (up to 80 mg) PO 60 minutes prior to chemotherapy (if applicable) for participants 6 months to <12 years of age
Drug: Emetogenic chemotherapy
Any moderately or highly emetic chemotherapeutic agent such as cyclophosphamide, doxorubicin, methotrexate, carboplatin, cisplatin, irinotecan, carmustine, ifosfamide, and streptozocin, or chemotherapeutics of a lower emetogenicity that were not previously tolerated. No chemotherapeutic agents were specified by the protocol, and many could potentially have been used."

  Eligibility

Ages Eligible for Study:   6 Months to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Cycle 1:

  • Is 6 months to 17 years of age at time of study entry
  • Is scheduled to receive chemotherapeutic agent(s) associated with moderate, high risk or very high risk of vomiting for a documented malignancy, or a chemotherapy regimen not previously tolerated due to vomiting
  • Is expected to receive ondansetron as part of their antiemetic regimen
  • If female and has begun menses, must has a negative urine pregnancy test prior to

randomization. A female who is of reproductive potential agrees to remain abstinent or use a barrier form of contraception for at least 14 days prior to, throughout, and for at least one month following the last dose of study medication

  • If >10 years old, have a Karnofsky score ≥ 60; if ≤ 10 years have a Lansky Play Performance score ≥ 60
  • Have a predicted life expectancy of ≥ 3 months

Optional Cycles 2-6:

  • Participant has, in the opinion of the investigator, completed the preceding cycle of chemotherapy and related study procedures satisfactorily

Exclusion Criteria:

Cycle 1:

  • Has vomited in the 24 hours prior to Treatment Day 1
  • Is scheduled to receive stem cell rescue therapy in conjunction with study related course(s) of emetogenic chemotherapy
  • Has received or will receive radiation therapy to the abdomen or pelvis within a week prior to Treatment Day 1 or during the course of the study
  • Is pregnant or breast feeding
  • Is allergic to aprepitant, ondansetron, or any other 5-hydroxytryptamine type-3 receptor (5-HT3) antagonist
  • Has a symptomatic primary or metastatic CNS malignancy causing nausea and/or vomiting
  • History of QT prolongation or taking other medicinal products that lead to QT prolongation
  • Has an active infection (e.g., pneumonia), congestive heart failure, bradyarrhythmia, or any uncontrolled disease (e.g., diabetic ketoacidosis, gastrointestinal obstruction) except for malignancy, which in the opinion of the investigator, might confound the results of the study or pose unwarranted risk in administering study drug to the participant
  • Has had benzodiazepine or opioid therapy initiated within 48 hours of study drug administration, except for single daily doses of triazolam, temazepam, or midazolam
  • Has been started on systemic corticosteroid therapy within 72 hours prior to study drug administration or is planned to receive a corticosteroid as part of the chemotherapy regimen
  • Is currently taking warfarin

Optional Cycles 2-6:

  • All exclusion criteria from Cycle 1 apply except for vomiting in the 24 hours prior to Treatment Day 1
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01362530

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01362530     History of Changes
Other Study ID Numbers: 0869-208
Study First Received: May 26, 2011
Results First Received: February 24, 2014
Last Updated: August 25, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Nausea
Vomiting
Signs and Symptoms
Signs and Symptoms, Digestive
Aprepitant
Fosaprepitant
Ondansetron
Anti-Anxiety Agents
Antiemetics
Antipruritics
Antipsychotic Agents
Autonomic Agents
Central Nervous System Agents
Central Nervous System Depressants
Dermatologic Agents
Gastrointestinal Agents
Molecular Mechanisms of Pharmacological Action
Neurokinin-1 Receptor Antagonists
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Agents
Serotonin Antagonists
Therapeutic Uses
Tranquilizing Agents

ClinicalTrials.gov processed this record on November 24, 2014