Olanzapine for Prevention of Chemotherapy-induced Nausea and Vomiting in Children: A Multi-Centre Feasibility Study
Condition: Chemotherapy-induced Nausea and Vomiting
MeSH terms: Nausea; Vomiting
Intervention: Olanzapine
Intervention description: Patients will receive olanzapine once daily starting just before the first dose of chemotherapy within the study chemotherapy block and continuing until discharge from hospital or for a maximum of 4 doses after the last dose of chemotherapy.
Olanzapine will be dosed at 0.14mg/kg/dose (maximum 10mg/dose) as a single daily oral dose rounded to the nearest increment of a half-tablet (2.5mg).
Intervention MeSH terms: Olanzapine
Phase: Phase 2
Study type: Interventional
Primary purpose: Supportive Care
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 15.0
Sex: All
Minimum age: 4 Years
Maximum age: 18 Years
Healthy volunteers: No
Keywords: olanzapine; pediatrics; chemotherapy-induced nausea; chemotherapy-induced vomiting

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