RCT of Olanzapine for Control of CIV in Children Receiving Highly Emetogenic Chemotherapy

Overview

Chemotherapy-induced nausea and vomiting (CINV) are among the most bothersome symptoms during cancer treatment according to children and their parents. Most children receiving highly emetogenic chemotherapy (HEC), including those receiving hematopoietic stem cell transplant (HSCT) conditioning, experience CIV despite receiving antiemetic prophylaxis. Olanzapine improves CINV control in adult cancer patients, has a track record of safe use in children with psychiatric illness, does not interact with chemotherapy and is inexpensive. We hypothesize that the addition of olanzapine to standard antiemetics will improve chemotherapy-induced vomiting (CIV) control in children receiving highly emetogenic chemotherapy

Full Title of Study: “Randomized Controlled Trial of Olanzapine for the Control of Chemotherapy-induced Vomiting in Children Receiving Highly Emetogenic Chemotherapy”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Supportive Care
    • Masking: Triple (Participant, Care Provider, Investigator)
  • Study Primary Completion Date: March 2025

Interventions

  • Drug: Olanzapine
    • olanzapine 0.1 mg/kg/dose (maximum 10 mg/dose) by mouth as a single daily dose based on actual body weight
  • Drug: Placebo Oral Tablet
    • Placebo tablets that look like olanzapine and will be dosed as if they are olanzapine

Arms, Groups and Cohorts

  • Active Comparator: Olanzapine
    • Standard antiemetics plus olanzapine
  • Placebo Comparator: Placebo Oral Tablet
    • Standard antiemetics plus placebo

Clinical Trial Outcome Measures

Primary Measures

  • Rate of CIV control during the acute phase
    • Time Frame: up to 8 days
    • Complete CIV control is no vomiting/retching and no use of breakthrough antiemetic agents during phase
  • Rate of CIV control during the acute phase
    • Time Frame: up to 8 days
    • Partial control is defined as no more than two vomits or retches during any 24-hr period

Secondary Measures

  • complete and partial CINV control
    • Time Frame: up to 1 month
    • Complete CIV control is no vomiting/retching and no use of breakthrough antiemetic agents during phase, Partial control is defined as no more than two vomits or retches during any 24-hr period
  • Safety profile of olanzapine based on toxicities
    • Time Frame: up to 1 month
    • Based on descriptive statistics on reported toxicities.
  • Safety profile of olanzapine based on weight
    • Time Frame: up to 1 month
    • Based on descriptive statistics on reported body weight
  • Safety profile of olanzapine based on Pediatric Adverse Event Rating Scale (PAERs)
    • Time Frame: up to 1 month
    • Based on descriptive statistics on reported PAERs, will describe the most reported and most bothersome adverse events reported in the PAERs questionnaire.
  • Safety profile of olanzapine based on prolactin
    • Time Frame: up to 1 month
    • Based on descriptive statistics on reported prolactin, will report incidence of abnormal prolactin values comparing the two arms
  • Safety profile of olanzapine based on amylase
    • Time Frame: up to 1 month
    • Based on descriptive statistics on reported amylase, will report incidence of abnormal amylase values comparing the two arms
  • Safety profile of olanzapine based on creatine phophotase
    • Time Frame: up to 1 month
    • Based on descriptive statistics on reported creatine phophotase, will report incidence of abnormal creatine phophotase values comparing the two arms
  • Safety profile of olanzapine based on triglycerides
    • Time Frame: up to 1 month
    • Based on descriptive statistics on reported triglycerides, will report incidence of abnormal triglyceride values comparing the two arms
  • Impact of olanzapine on HSCT outcomes on incidence of veno-occlusive disease
    • Time Frame: From first HSCT conditioning dose until 100 days post-HSCT
    • Looking at incidence of veno-occlusive disease
  • Impact of olanzapine on HSCT outcomes on incidence of GVHD
    • Time Frame: From first HSCT conditioning dose until 100 days post-HSCT
    • Looking at incidence of GVHD between the two arms
  • Impact of olanzapine on HSCT outcomes on severity of GVHD
    • Time Frame: From first HSCT conditioning dose until 100 days post-HSCT
    • Comparing the incidence of the different maximal grades of GVHD between the two arms
  • Association between PeNAT and MASCC Antiemesis Tool (MAT) scores
    • Time Frame: up to 1 month
    • taking maximum daily PeNAT scale score and maximum nausea experience in MAT will estimate the degree of association between PeNAT and MAT

Participating in This Clinical Trial

Planned receipt of HEC or cyclophosphamide ≥ 1 g/m2/day (≥ 33 mg/kg/day) for cancer treatment or autologous or allogeneic HSCT conditioning.81,82 Examples of HEC are: busulfan IV (myeloablative dosing), carboplatin ≥175mg/m²/dose, cisplatin ≥12mg/m²/dose, cytarabine ≥3g/m²/day, melphalan >140mg/m², methotrexate ≥12g/m²/dose and thiotepa ≥300mg/m²/dose. Plan for inpatient admission from administration of first study drug dose until 24 hours following administration of last study drug dose. Body weight of at least 12.5 kg 2.5 to < 18 years of age. Note that the minimum age requirement corresponds to an approximate body weight of 12.5 kg. Samples for all laboratory tests will be obtained within one week prior to administration of the first chemotherapy dose of the study chemotherapy block or the first HSCT conditioning dose:

  • Plasma creatinine within 1.5 times the upper limit of normal for age. – Amylase within age-appropriate limits – Plasma conjugated bilirubin within ≤ 3x upper limit of normal for age unless attributable to Gilbert's Syndrome – ALT ≤ 5x upper limit of normal for age Baseline ECG within the month prior to study drug administration without known clinically significant abnormalities including pathologic prolongation of QTc A plan for scheduled, round-the-clock receipt of ondansetron, granisetron or palonosetron for antiemetic prophylaxis during administration of chemotherapy or HSCT conditioning. Negative pregnancy test if female of childbearing potential Patients of childbearing potential must consent to use adequate contraception (males and females) or agree to practice abstinence Parent or child able to speak a language in which the (modified Pediatric Adverse Event Rating Scale (PAERS) is available. Optional: Child participants in the optional assessment of nausea severity must be 4 to 18 years of age. Child and a parent/guardian must be English, Spanish or French-speaking. The Pediatric Nausea Assessment Tool58 (PeNAT) is validated in English-speaking children 4 to 18 years old with an English-speaking parent/guardian and has been translated into Spanish and French. The MAT is available in English, Spanish and French.

Gender Eligibility: All

Minimum Age: 30 Months

Maximum Age: 18 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • The Hospital for Sick Children
  • Collaborator
    • University of California, San Francisco
  • Provider of Information About this Clinical Study
    • Principal Investigator: Lee Dupuis, Principal Investigator – The Hospital for Sick Children
  • Overall Official(s)
    • Lee Dupuis, RPh, PhD, Principal Investigator, The Hospital for Sick Children
    • Muhammad Ali, MD, Principal Investigator, The Hospital for Sick Children
  • Overall Contact(s)
    • Lee Dupuis, RPh, PhD, 416-813-7762, lee.dupuis@sickkids.ca

References

Dupuis LL, Taddio A, Kerr EN, Kelly A, MacKeigan L. Development and validation of the pediatric nausea assessment tool for use in children receiving antineoplastic agents. Pharmacotherapy. 2006 Sep;26(9):1221-31. doi: 10.1592/phco.26.9.1221.

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.