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

Nausea Clinical Trial

Official title:

Randomized Controlled Trial of Olanzapine for the Control of Chemotherapy-induced Vomiting in Children Receiving Highly Emetogenic Chemotherapy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03118986
• Other study ID #: 1000053716
• Status: Recruiting
• Phase: Phase 2
• Start date: August 10, 2017
• Est. completion date: April 2025

Study information

• Verified date: March 2024
• Source: The Hospital for Sick Children
• Contact: Lee Dupuis, RPh, PhD
• Phone: 416-813-7762
• Email: lee.dupuis[@]sickkids.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: April 2025
• Est. primary completion date: March 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Months to 18 Years

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

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

Locations

Country	Name	City	State
Canada	Centre Hospitalier Universitaire Sainte-Justine,	Montréal	Quebec
Canada	Hospital for Sick Children	Toronto	Ontario
Canada	Cancer Care Manitoba	Winnipeg	Manitoba
India	All India Institute of Medical Sciences	New Delhi	Delhi
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	The Children's Mercy Hospital	Kansas City	Missouri
United States	Columbia University/Morgan Stanley Children's Hospital	New York	New York
United States	The University Of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	University of California	San Francisco	California

Sponsors (9)

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

Countries where clinical trial is conducted

United States,  Canada,  India, 

References & 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	complete and partial CINV control	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	up to 1 month
Secondary	Safety profile of olanzapine based on toxicities	Based on descriptive statistics on reported toxicities.	up to 1 month
Secondary	Safety profile of olanzapine based on weight	Based on descriptive statistics on reported body weight	up to 1 month
Secondary	Safety profile of olanzapine based on Pediatric Adverse Event Rating Scale (PAERs)	Based on descriptive statistics on reported PAERs, will describe the most reported and most bothersome adverse events reported in the PAERs questionnaire.	up to 1 month
Secondary	Safety profile of olanzapine based on prolactin	Based on descriptive statistics on reported prolactin, will report incidence of abnormal prolactin values comparing the two arms	up to 1 month
Secondary	Safety profile of olanzapine based on amylase	Based on descriptive statistics on reported amylase, will report incidence of abnormal amylase values comparing the two arms	up to 1 month
Secondary	Safety profile of olanzapine based on creatine phophotase	Based on descriptive statistics on reported creatine phophotase, will report incidence of abnormal creatine phophotase values comparing the two arms	up to 1 month
Secondary	Safety profile of olanzapine based on triglycerides	Based on descriptive statistics on reported triglycerides, will report incidence of abnormal triglyceride values comparing the two arms	up to 1 month
Secondary	Impact of olanzapine on HSCT outcomes on incidence of veno-occlusive disease	Looking at incidence of veno-occlusive disease	From first HSCT conditioning dose until 100 days post-HSCT
Secondary	Impact of olanzapine on HSCT outcomes on incidence of GVHD	Looking at incidence of GVHD between the two arms	From first HSCT conditioning dose until 100 days post-HSCT
Secondary	Impact of olanzapine on HSCT outcomes on severity of GVHD	Comparing the incidence of the different maximal grades of GVHD between the two arms	From first HSCT conditioning dose until 100 days post-HSCT
Secondary	Association between PeNAT and MASCC Antiemesis Tool (MAT) scores	taking maximum daily PeNAT scale score and maximum nausea experience in MAT will estimate the degree of association between PeNAT and MAT	up to 1 month