Clinical trial NCT03118986: RCT of Olanzapine for Control of CIV in Children Receiving Highly Emetogenic Chemotherapy
Official title: Randomized Controlled Trial of Olanzapine for the Control of Chemotherapy-induced Vomiting in Children Receiving Highly Emetogenic Chemotherapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Vomiting in Infants and/or Children
Nausea
Hematopoietic System--Cancer
Oncology
Keywords: olanzapine
vomiting
children
adolescents
bone marrow transplant
supportive care
Lead sponsor: The Hospital for Sick Children
Sponsor class: OTHER
Collaborators: name: University of California, San Francisco
name: Children's Mercy Hospital Kansas City
name: St. Justine's Hospital
name: Columbia University
name: Medical University of South Carolina
name: CancerCare Manitoba
name: University of North Carolina, Chapel Hill
name: Nationwide Children's Hospital
First posted: 2017-04-18
Enrollment: 200
Sex: ALL
Minimum age (years): 30
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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


Eligibility criteria: 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.

Primary outcomes:
measure: Rate of CIV control during the acute phase
timeFrame: up to 8 days
measure: Rate of CIV control during the acute phase
timeFrame: up to 8 days
Secondary outcomes:
measure: complete and partial CINV control
timeFrame: up to 1 month
measure: Safety profile of olanzapine based on toxicities
timeFrame: up to 1 month
measure: Safety profile of olanzapine based on weight
timeFrame: up to 1 month
measure: Safety profile of olanzapine based on Pediatric Adverse Event Rating Scale (PAERs)
timeFrame: up to 1 month
measure: Safety profile of olanzapine based on prolactin
timeFrame: up to 1 month
measure: Safety profile of olanzapine based on amylase
timeFrame: up to 1 month
measure: Safety profile of olanzapine based on creatine phophotase
timeFrame: up to 1 month
measure: Safety profile of olanzapine based on triglycerides
timeFrame: up to 1 month
measure: Impact of olanzapine on HSCT outcomes on incidence of veno-occlusive disease
timeFrame: From first HSCT conditioning dose until 100 days post-HSCT
measure: Impact of olanzapine on HSCT outcomes on incidence of GVHD
timeFrame: From first HSCT conditioning dose until 100 days post-HSCT
measure: Impact of olanzapine on HSCT outcomes on severity of GVHD
timeFrame: From first HSCT conditioning dose until 100 days post-HSCT
measure: Association between PeNAT and MASCC Antiemesis Tool (MAT) scores
timeFrame: up to 1 month
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California
state: California
city: Kansas City
country: United States
facility: The Children's Mercy Hospital
state: Missouri
city: New York
country: United States
facility: Columbia University/Morgan Stanley Children's Hospital
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Winnipeg
country: Canada
facility: Cancer Care Manitoba
state: Manitoba
city: Toronto
country: Canada
facility: Hospital for Sick Children
state: Ontario
city: Montréal
country: Canada
facility: Centre Hospitalier Universitaire Sainte-Justine,
state: Quebec
city: New Delhi
country: India
facility: All India Institute of Medical Sciences
state: Delhi
Study officials:
affiliation: The Hospital for Sick Children
name: Lee Dupuis, RPh, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Hospital for Sick Children
name: Muhammad Ali, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.