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

NCT03118986 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 1000053716
• Study Type: interventional
• Target: 200
• Locations: 3 countries
• Sites: 10

Brief Summary

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

Conditions

Vomiting in Infants and/or Children; Nausea; Hematopoietic System--Cancer; Oncology

Keywords

olanzapine; vomiting; children; adolescents; bone marrow transplant; supportive care

Outcome Measures

Primary Outcomes (2)

• Rate of CIV control during the acute phase

  Complete CIV control is no vomiting/retching and no use of breakthrough antiemetic agents during phase

  up to 8 days

• Rate of CIV control during the acute phase

  Partial control is defined as no more than two vomits or retches during any 24-hr period

  up to 8 days

Secondary Outcomes (12)

• complete and partial CINV control

  up to 1 month

• Safety profile of olanzapine based on toxicities

  up to 1 month

• Safety profile of olanzapine based on weight

  up to 1 month

• Safety profile of olanzapine based on Pediatric Adverse Event Rating Scale (PAERs)

  up to 1 month

• Safety profile of olanzapine based on prolactin

  up to 1 month

Study Arms (2)

Olanzapine

ACTIVE COMPARATOR

Standard antiemetics plus olanzapine

Drug: Olanzapine

Placebo Oral Tablet

PLACEBO COMPARATOR

Standard antiemetics plus placebo

Drug: Placebo Oral Tablet

Interventions

Olanzapine DRUG

olanzapine 0.1 mg/kg/dose (maximum 10 mg/dose) by mouth as a single daily dose based on actual body weight

Olanzapine

Placebo Oral Tablet DRUG

Placebo tablets that look like olanzapine and will be dosed as if they are olanzapine

Placebo Oral Tablet

Eligibility Criteria

• Age: 30 Months - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

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.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• The Hospital for Sick Children: lead
• University of California, San Francisco: collaborator
• Children's Mercy Hospital Kansas City: collaborator
• St. Justine's Hospital: collaborator
• Columbia University: collaborator
• Medical University of South Carolina: collaborator
• CancerCare Manitoba: collaborator
• University of North Carolina, Chapel Hill: collaborator
• Nationwide Children's Hospital: collaborator

Study Sites (10)

University of California

San Francisco, California, 94158, United States

RECRUITING

The Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

RECRUITING

Columbia University/Morgan Stanley Children's Hospital

New York, New York, 10032, United States

WITHDRAWN

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599-7220, United States

RECRUITING

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

RECRUITING

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

RECRUITING

Cancer Care Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

RECRUITING

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

RECRUITING

Centre Hospitalier Universitaire Sainte-Justine,

Montreal, Quebec, H3T 1C5, Canada

TERMINATED

All India Institute of Medical Sciences

New Delhi, National Capital Territory of Delhi, 110029, India

RECRUITING

Related Publications (1)

• 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.

  PMID: 16945043 BACKGROUND

MeSH Terms

Conditions

Nausea; Neoplasms; Vomiting

Interventions

Olanzapine

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Lee Dupuis, RPh, PhD

  The Hospital for Sick Children

  PRINCIPAL INVESTIGATOR

• Muhammad Ali, MD

  The Hospital for Sick Children

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lee Dupuis, RPh, PhD

CONTACT

416-813-7762; lee.dupuis@sickkids.ca

Muhammad Ali, MD

CONTACT

416-813-7654; muhammad.ali@sickkids.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 16, 2017
• First Posted: April 18, 2017
• Study Start: August 10, 2017
• Primary Completion: March 1, 2026
• Study Completion: April 1, 2026
• Last Updated: October 8, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1); US (6); CA (3)