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Olanzapine for Prevention of Chemotherapy-induced Nausea and Vomiting in Children: A Multi-Centre Feasibility Study

Phase 2
Completed
Conditions
Chemotherapy-induced Nausea and Vomiting
Interventions
Registration Number
NCT02129478
Lead Sponsor
The Hospital for Sick Children
Brief Summary

Olanzapine is licensed for use in adults in Canada and in teens in the US with mental illness. It is also often used for the management of mental illness in children. This study will describe the feasibility of giving olanzapine plus other usual medications to prevent chemotherapy induced nausea and vomiting (CINV) to 15 children aged 4 to 18 years.

What has been done already? - In adult cancer patients, olanzapine improved the control of CINV. None of the adults studied experienced any serious side effects from olanzapine.

What is being studied and how will the study be conducted? - On each day that chemotherapy is given, olanzapine will be given to 15 children along with their regular medications to prevent CINV. Investigators will study each child only during one chemotherapy cycle. Participants' blood sugar, liver function tests (AST and ALT), prolactin and triglyceride levels, blood pressure, weight, mood and behavior during the time they receive olanzapine will be evaluated to see if they change. Investigators will record anything serious that happens while children receive olanzapine. If any child stops olanzapine early or decides to decrease the dose, the reason will be recorded. Each child and their guardian will record their nausea severity and the times they vomit or retch on each day they receive chemotherapy and for 8 days afterwards.

How will the study help? - This study will help investigators decide if it is feasible to conduct a larger study to find out if olanzapine improves CINV control in children. If most children are able to take olanzapine as set out in the study without having significant side effects, then a larger study would be feasible.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
15
Inclusion Criteria
  • 4 to 18 years old
  • English-speaking and have an English-speaking parent/guardian
  • Have the minimum cognitive ability of a 4 year old as assessed by a health care professional
  • Scheduled to receive moderately to highly emetogenic chemotherapy as assessed using the Pediatric Oncology Group of Ontario Guideline for emetogenicity Classification of Antineoplastic Agents in Children on at least one day of a course of chemotherapy
  • Scheduled to receive either ondansetron, granisetron or palonosetron with or without dexamethasone on a scheduled basis as ordered by the patient's clinical team as per the usual antiemetic standard of care
  • Weigh at least 14kg
  • Have serum total bilirubin ≤ 3 mg/dl (50 µmol/L), and ALT and AST ≤ 3x upper limit of normal for age
  • Consent to use adequate contraception or remain abstinent on each day olanzapine is given and for 5 days afterward if of child-bearing potential
Exclusion Criteria
  • Brain tumor patients
  • Have had treatment within 14 days prior to study enrollment with olanzapine or 30 days prior to study enrollment with another antipsychotic agent
  • Planned to receive amifostine, CYP1A2 inducers or inhibitors, other antipsychotic agents or quinolone antibiotics while receiving olanzapine;
  • Have uncontrolled hypertension
  • Receive other antipsychotic agents, amifostine, citalopram, CYP1A2 inducers or inhibitors, quinolone antibiotics while receiving olanzapine
  • Receive scopolamine patches, phenothiazines, acupressure or acupuncture during the study period
  • Planned to receive any antiemetic agents other than dexamethasone, ondansetron, granisetron, palonosetron, aprepitant or fosaprepitant on a scheduled basis
  • Have a history of neuroleptic malignant syndrome, a seizure disorder, hypersensitivity to olanzapine, cardiac arrhythmias including prolonged QT, low left ventricular ejection fraction, or a history of uncontrolled diabetes mellitus
  • Are pregnant or breast-feeding

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
OlanzapineOlanzapine-
Primary Outcome Measures
NameTimeMethod
Patient Outcomes1 year

Our primary study outcome evaluated the feasibility of a future trial of olanzapine that would evaluate the contribution of olanzapine to chemotherapy-induced nausea and vomiting (CINV) control in pediatric oncology patients. A future trial was considered feasible if the following patient outcomes were met: mean time to enroll 15 patients was 12 months or less per site, 12 or more patients took at least half of the planned olanzapine doses, and 3 or less patients experienced significant sedation or dizziness despite dose reduction.

Secondary Outcome Measures
NameTimeMethod
Proportion of Patients With Complete CINV ControlDuring the acute (24 hours) and delayed (7 days after acute phase) phases, up to 2 weeks

The proportion of children achieving complete CINV control (no nausea, vomiting, or retching and no use of breakthrough antiemetic agents) during the acute (24 hours after the last dose of chemotherapy is administered) and delayed phases (the 7 days following the acute phase) will be described. The duration of assessment will depend on the number of days each individual patient receives chemotherapy. Nausea will be assessed using the Pediatric Nausea Assessment Tool (PeNAT).

Number of Participants With Adverse Events as a Measure of Safety and TolerabilityEvery day for 30 days after the last dose of the study drug

All early discontinuation of olanzapine or dose reduction cases will be reported.

Trial Locations

Locations (3)

Children's Hospital, London Health Sciences Centre

🇨🇦

London, Ontario, Canada

Children's Hospital of Eastern Ontario

🇨🇦

Ottawa, Ontario, Canada

The Hospital for Sick Children

🇨🇦

Toronto, Ontario, Canada

Children's Hospital, London Health Sciences Centre
🇨🇦London, Ontario, Canada
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