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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Breast Cancer

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 |