Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting in Chinese Breast Cancer Patients

A Randomized Study to Determine the Efficacy and Tolerability of Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting in Chinese Breast Cancer Patients

The Olanzapine Regimen will be superior to the Standard Regimen, as measured by the proportion of patients with Complete Response in the 120 hours following AC chemotherapy.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Experimental drug: Aprepitant; Drug: Experimental drug: Ondansetron; Drug: Experimental drug: Dexamethasone; Drug: Experimental drug: Olanzapine; Drug: Standard: Aprepitant; Drug: Standard: Ondansetron; Drug: Standard: Dexamethasone

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 3

Contacts and Locations

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Department of Clinical Oncology, Prince of Wales Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 74 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Chinese patient, female >=18 and < 75 years of age.
• Patient is diagnosed with early breast cancer.
• Patient is naïve to emetogenic chemotherapy moderately or highly emetogenecity.
• Patient is scheduled to receive her first course of adjuvant chemotherapy for breast cancer follows:
• IV adriamycin 60 mg/m2 + cyclophosphamide 600 mg/m2
• Patient has a predicted life expectancy of >=4 months.
• Patient has ECOG Performance Status of 0-1
• Premenopausal female patients must not be pregnant (documented negative urine pregnancy test).
• Patient is able to read, understand and complete study questionnaires and diary, including questions requiring a visual analog scale (VAS) response.
• Patient understands the procedures and agrees to participate in the study by giving written informed consent

Exclusion Criteria:

• Patient with advanced breast cancer.
• Patient receiving cisplatin or any other chemotherapy of higher emetogenic potential, except for cyclophosphamide and doxorubicin in the regimens described above.
• Patients who are scheduled to receive concurrent radiation as part of their chemotherapy regimen for their malignancy
• Patients who experience any vomiting or grade 2-3 nausea per Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v 4.03) in the 24 hours before Day 1 of chemotherapy
• Patient has a history of treatment with moderately to highly emetogenic chemotherapy.
• Patient has an active infection (e.g., pneumonia, systemic fungal infection) or any uncontrolled disease (e.g., diabetes mellitus, hypertension) which, in the opinion of the investigator, might confound the results of the study or pose unwarranted risk.
• Patient with history of glaucoma, dementia, seizures, Parkinson's disease, Neuroleptic Malignant Syndrome (NMS), thromboembolic events.
• Patient currently uses any illicit drugs, including marijuana, or has current evidence of alcohol abuse as determined by the investigator.
• Patient is mentally incapacitated or has a significant emotional or psychiatric disorder that, in the opinion of the investigator, precludes study entry.
• Patients who are regular alcohol drinker or smoker
• Patient has a history of any illness that, in the opinion of the investigator, might confound the results of the study or pose unwarranted risk.
• Patient has a history of hypersensitivity to aprepitant, ondansetron or dexamethasone.
• Patients who have phenylketonuria and abnormal uric acid.
• Any investigational drugs taken within 4 weeks prior to Day 1 of cycle 1, and/or is scheduled to receive any investigational drug during the study;
• Patient is taking systemic corticosteroid therapy at any dose; however, topical and inhaled corticosteroids are permitted.
• Patient has taken a non-registered investigational drug within the 28 days of the Prestudy Visit.
• Use, in the 28 days prior to Treatment Day 1, of barbiturates, rifampicin or rifabutin, phenytoin or carbamazepine
• Use, in the 7 days prior to Treatment Day 1, of terfenadine, cisapride, astemizole, clarithromycin (azithromycin, erythromycin and roxithromycin are permitted), ketoconazole or itraconazole (fluconazole is permitted), amifostine pimozide 5-HT3 antagonists (ondansetron, granisetron, dolasetron, or tropisetron) phenothiazines (e.g., prochlorperazine, fluphenazine, perphenazine, thiethylperazine, or chlorpromazine) butyrophenones (e.g., haloperidol or droperidol) benzamides (e.g., metoclopramide or alizapride) domperidone cannabinoids NK1 receptor antagonists

• Use, in the 48 hours prior to Treatment Day 1, of benzodiazepines or opiates, except for single daily doses of lorazepam.

  s. Use of the following drugs: carbamazepine Fluvoxamine ciprofloxacin dopamine agonists. antiparkinsonian medicinal products medicinal products known to increase QTc interval t. Abnormal laboratory values

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental; Aprepitant, Ondansetron, Dexamethasone and Olanzapine	Drug: Experimental drug: Aprepitant; Day 1: 125mg QD; Day 2 to Day 3: 80mg QD; Drug: Experimental drug: Ondansetron; Day 1: 8mg BD, First dose 8mg, Second dose 8mg, 8 hours after first dose; Drug: Experimental drug: Dexamethasone; Day 1: 12mg QD; Drug: Experimental drug: Olanzapine; Day 1 to Day 5: 10mg QD
Other: Standard; Aprepitant, Ondansetron, Dexamethasone	Drug: Standard: Aprepitant; Day 1: 125mg QD, Day 2 to Day3: 80mg QD; Drug: Standard: Ondansetron; Day 1: 8mg BD, First dose 8mg, second dose 8mg, 8 hours after first dose; Drug: Standard: Dexamethasone; Day 1: 12mg QD ; Day 2 to Day 3: 4mg BD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of episodes of nausea in the first 120 hours after first cycle of chemotherapy.	Number of episodes of nausea in the first 120 hours after first cycle of chemotherapy.	120 hours
Number of episodes of vomiting in the first 120 hours after first cycle of chemotherapy.	Number of episodes of vomiting in the first 120 hours after first cycle of chemotherapy.	120 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of episodes of nausea in the first 120 hours during 4 cycles of chemotherapy.	Number of episodes of nausea in the first 120 hours during 4 cycles of chemotherapy.	120 hours
Number of episodes of vomiting in the first 120 hours during 4 cycles of chemotherapy.	Number of episodes of vomiting in the first 120 hours during 4 cycles of chemotherapy.	120 hours

Collaborators and Investigators

• Sponsor: CCTU
• Investigators: Principal Investigator: Winnie Yeo, MD, FRCP, Chinese University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2017
• Primary Completion (Actual): March 1, 2021
• Study Completion (Actual): March 1, 2021

Study Registration Dates

• First Submitted: February 8, 2017
• First Submitted That Met QC Criteria: March 8, 2017
• First Posted (Actual): March 14, 2017

Study Record Updates

• Last Update Posted (Actual): July 28, 2021
• Last Update Submitted That Met QC Criteria: July 26, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Signs and Symptoms, Digestive; Breast Diseases; Breast Neoplasms; Vomiting; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protease Inhibitors; Dermatologic Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Serotonin Antagonists; Anti-Anxiety Agents; Antipruritics; Neurokinin-1 Receptor Antagonists; Dexamethasone; Dexamethasone acetate; BB 1101; Olanzapine; Ondansetron; Aprepitant; Fosaprepitant
• Other Study ID Numbers: SYM010

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No