Clinical trial NCT02129478: Olanzapine for Prevention of Chemotherapy-induced Nausea and Vomiting in Children: A Multi-Centre Feasibility Study
Official title: Olanzapine for Prevention of Chemotherapy-induced Nausea and Vomiting in Children: A Multi-Centre Feasibility Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chemotherapy-induced Nausea and Vomiting
Keywords: olanzapine
pediatrics
chemotherapy-induced nausea
chemotherapy-induced vomiting
Lead sponsor: The Hospital for Sick Children
Sponsor class: OTHER
Collaborators: name: Pediatric Oncology Group of Ontario
First posted: 2014-05-02
Enrollment: 15
Sex: ALL
Minimum age (years): 4
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

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.


Eligibility criteria: 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

Primary outcomes:
measure: Patient Outcomes
timeFrame: 1 year
Secondary outcomes:
measure: Proportion of Patients With Complete CINV Control
timeFrame: During the acute (24 hours) and delayed (7 days after acute phase) phases, up to 2 weeks
measure: Number of Participants With Adverse Events as a Measure of Safety and Tolerability
timeFrame: Every day for 30 days after the last dose of the study drug
Other outcomes:
Locations:
city: London
country: Canada
facility: Children's Hospital, London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: Children's Hospital of Eastern Ontario
state: Ontario
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
Study officials:
affiliation: The Hospital for Sick Children
name: Lee Dupuis, RPh, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Flank J, Schechter T, Gibson P, Johnston DL, Orsey AD, Portwine C, Sung L, Dupuis LL. Olanzapine for prevention of chemotherapy-induced nausea and vomiting in children and adolescents: a multi-center, feasibility study. Support Care Cancer. 2018 Feb;26(2):549-555. doi: 10.1007/s00520-017-3864-8. Epub 2017 Aug 30.