Olanzapine for the Prevention of Chemotherapy Induced Nausea and Vomiting in Gynecologic Oncology Patients

Study Overview
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Brief Summary
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The objective of this study is to investigate the efficacy of olanzapine as compared to neurokinin-1 receptor antagonists (NK1-RAs) in the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients with gynecologic malignancies receiving single day outpatient chemotherapy (carboplatin and paclitaxel) every 3 weeks.

Official Title
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Phase III Randomized Control Trial Investigating Olanzapine for the Prevention of Chemotherapy Induced Nausea and Vomiting in Patients With Gynecologic Malignancies Receiving Every 3-week Carboplatin and Paclitaxel Chemotherapy

Conditions
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Gynecologic Cancer

Intervention / Treatment
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* Drug: Ondansetron
* Drug: Dexamethasone
* Drug: Neurokinin-1 Receptor Antagonist (NK1-RA)
* Drug: Olanzapine
* Drug: Compazine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of gynecologic malignancy No chemotherapy in the last 12 months Scheduled to receive Carboplatin (AUC>=4) and Paclitaxel every three weeks ECOG performance status 0 or 1 English speaking Willing and able to provide informed consent Laboratory values within protocol-defined parameters No vomiting in the 24 hours prior to initiating chemotherapy If childbearing potential exists, negative pregnancy test within 7 days prior to registration Exclusion Criteria: Significant cognitive compromise History of CNS disease (e.g. brain metastases, seizure disorder, dementia) Current or recent (within 30 days) treatment with another antipsychotic agent (antidepressant medications are OK) Concurrent radiotherapy treatment Known hypersensitivity to olanzapine Known cardiac arrhythmia, uncontrolled congestive heart failure or acute myocardial infarction within the last six months History of diabetes mellitus on medication (insulin or oral glycemic agent) Alcohol abuse / chronic alcoholism History of closed angle glaucoma Current enrollment in other clinical trials

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 89 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Nk1-RA<br>Nk1-RA will be given on day 1 of each 3-week chemotherapy cycle, for up to 6 cycles. | Drug: Ondansetron<br>* 8 mg IV or 16 mg by mouth on day 1 pre-chemotherapy; then 8 mg by mouth twice a day on days 2-4 of chemotherapy<br>Drug: Dexamethasone<br>* 20 mg IV on day 1 pre-chemotherapy<br>Drug: Neurokinin-1 Receptor Antagonist (NK1-RA)<br>* 150 mg IV on day 1 pre-chemotherapy<br>* Other names: Fosaprepitant;Drug: Compazine<br>* 5-10 mg by mouth, available as needed, every 6 hours, days 1-5<br>|
| Experimental: Olanzapine<br>Olanzapine will be given on days 1-4 of each 3-week chemotherapy cycle, for up to 6 cycles. | Drug: Ondansetron<br>* 8 mg IV or 16 mg by mouth on day 1 pre-chemotherapy; then 8 mg by mouth twice a day on days 2-4 of chemotherapy<br>Drug: Dexamethasone<br>* 20 mg IV on day 1 pre-chemotherapy<br>Drug: Olanzapine<br>* 5 mg by mouth on days 1-4 of chemotherapy (taken at night)<br>* Other names: Zyprexa;Drug: Compazine<br>* 5-10 mg by mouth, available as needed, every 6 hours, days 1-5<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of complete response in the overall time period (0 - 120 hours post-chemotherapy) | Complete response (CR) is defined as no episodes of vomiting and no use of rescue antiemetic medications. Patient reported diaries will be used to measure this outcome. | At day 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of complete response in the acute time period (0 - 24 hours post-chemotherapy) | Complete response (CR) is defined as no episodes of vomiting and no use of rescue antiemetic medications. Patient reported diaries will be used to measure this outcome. | At day 2 | 
| Rate of complete response in the delayed time period (24 - 120 hours post-chemotherapy) | Complete response (CR) is defined as no episodes of vomiting and no use of rescue antiemetic medications. Patient reported diaries will be used to measure this outcome. | At day 6 | 
| Rate of no nausea in the acute time period (0 - 24 hours post-chemotherapy) | Patients will record daily levels of nausea after chemotherapy using a Likert scale ranging from 0-10 (0 indicating no nausea; 10 indicating maximum level of nausea). | At day 2 | 
| Rate of no nausea in the delayed time period (24 - 120 hours post-chemotherapy) | Patients will record daily levels of nausea using a Likert scale ranging from 0-10 (0 indicating no nausea; 10 indicating maximum level of nausea). | At day 6 | 
| Rate of no nausea in the overall time period (0 - 120 hours post-chemotherapy) | Patients will record daily levels of nausea using a Likert scale ranging from 0-10 (0 indicating no nausea; 10 indicating maximum level of nausea). | At day 6 | 
| Mean somnolence score | Patients will record daily levels of undesired sedation using a Likert scale ranging from 0 to 10 (0 indicating no undesired sedation; 10 indicating maximum level of undesired sedation). | At day 6 | 
| Mean increased-appetite score | Patients will record daily levels of undesired increase in appetite using a Likert scale ranging from 0 to 10 (0 indicating no undesired increase in appetite; 10 indicating maximum level of undesired increase in appetite). | At day 6 |