"Olanzapine for Prevention of Chemotherapy Induced Nausea and Vomiting in Children and Adolescents Receiving Highly Emetogenic Chemotherapy (HEC)"
Condition: Chemotherapy-induced Nausea and Vomiting
MeSH terms: Nausea; Vomiting
Study type: Interventional
Phase: Phase 3

Summary: 
      Chemotherapy induced nausea and vomiting (CINV) is one of the most distressing toxicities of
      cancer treatment. It can occur up to 90% in case of highly emetogenic chemotherapy (HEC) use.
      It is important to effectively manage CINV for a number of reasons. Acute phase vomiting can
      lead to vomiting in the delayed phase. It causes poor compliance with further therapy.
      Quality of life is compromised. It is easier to prevent nausea/vomiting than to treat it.
      Though strategies for prevention of CINV have been improved, it is still a significant
      problem. Newer drugs were explored and studied. The complete response rates were further
      increased with usage of olanzapine, an FDA approved antipsychotic, which blocks multiple
      neurotransmitters in the central nervous system.

      Olanzapine has been studied in multiple randomized trials in adults for its safety and
      efficacy in prevention of CINV. Various RCTs have demonstrated the superiority of olanzapine
      for prevention of CINV in patients receiving highly and moderately emetogenic chemotherapy.
      Olanzapine has been approved for prevention of CINV in adults.

      Unfortunately there are no large randomized trials demonstrating the efficacy of olanzapine
      for CINV prevention in children receiving HEC. The positive experience with olanzapine
      reported in adult oncology patients has prompted some pediatric clinicians to prescribe
      olanzapine for individual children receiving chemotherapy. Olanzapine is frequently used for
      the treatment of schizophrenia and bipolar disorder in children and adolescents. Though
      various studies have demonstrated safety of olanzapine in children, data regarding the
      efficacy of olanzapine in children and adolescents for prevention of CINV is limited. There
      are many small studies describing the safety and efficacy of olanzapine for prevention of
      CINV. However, there are no large randomized trials. Olanzapine is available in generic form
      and is not an expensive drug. Therefore we would like to conduct a randomized trial to look
      for the efficacy of olanzapine in pediatric population for prevention of CINV
    

Detailed description: 
      Children and adolescents registered with confirmed diagnosis of cancer will be assessed for
      eligibility criteria and enrolled in the study. Subjects will be randomized into study and
      control groups using table of random numbers generated by computer. Sequentially numbered,
      opaque, sealed envelopes will be used for concealed allocation. After randomization, subjects
      will be interviewed 1 hour prior 1st dose of chemotherapy. Subjects will receive the
      antiemetic drugs for four days as per the allotted arm. All doses will be administered under
      supervision and 30 minutes before chemotherapy. The data will be collected from each patient
      from day 1 to day5 from the last dose of chemotherapy. The details will contain different
      items dealing with demographic and clinical characteristic of the subjects. A Diary will be
      maintained for nausea and vomiting episodes. It will help in collecting data regarding
      nausea, vomiting along with some additional variables like chemotherapy related toxicities,
      requirement of any rescue medication. The subjects will be given the diary for symptom
      assessment on day 1 and it will be filled up under the supervision of the investigator on day
      1 till completion of chemotherapy. The diary will be given to the subjects following the
      completion of chemotherapy to record all the events (incidence and severity of nausea,
      vomiting, requirement of rescue medication and other toxicities ) and will be contacted by
      phone or in person by the investigator. Edmonton's symptom assessment criterion will be used
      in the diary for assessing severity of nausea. The NCI's CTCAEv4.03 criterion will be used to
      assess the severity of vomiting and adverse events based on the data provided by the patient
      in the diary. Patients/attendants will be explained about the filling of the diary and will
      maintain it for recording of vomiting. A modified intention-to-treat population will be used
      for efficacy analysis. Proportion of patients with CR during acute phase, delayed phase and
      overall period will be compared between the two arms.
    

Intervention name(s): Ondansetron; Dexamethasone; Aprepitant; Olanzapine
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Ondansetron will be given at a dosage of 0.15mg/kg IV/PO q8h.; Dexamethasone will be given as 3mg/m2 IV/PO q8h.; Aprepitant will be given as per the weight. weight (15-40kg) - Day1 to Day 3 - 80 mg PO weight (>40 kg) - Day 1 -125mg , Day 2 & Day 3 - 80 mg PO; olanzapine will be given as 0.14mg/kg PO (rounded off to nearest 2.5 mg )
Intervention MeSH terms: Dexamethasone; Ondansetron; Olanzapine; Aprepitant
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Supportive Care
Keywords: Chemotherapy induced nausea and vomiting; olanzapine