Steroid-sparing Therapy (Olanzapine) Versus Dexamethasone-based Therapy for Chemotherapy-induced Nausea and Vomiting

Study Overview
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Brief Summary
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The purpose of this research is to compare two drugs that are routinely used as standard of care for treating nausea and vomiting caused by chemotherapy. This study aims to see if the drug olanzapine is as good as the steroid drug dexamethasone for preventing nausea and vomiting after chemotherapy. Both drugs are listed as appropriate treatment options in the most recent version of National Comprehensive Cancer Network guidelines on Antiemesis.

Detailed Description
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The study will include patients treated with high emetogenic chemotherapy (HEC) or moderate emetogenic chemotherapy (MEC). Emetogenic means that it may cause nausea and vomiting. Your participation will last for 2 cycles of chemotherapy. For patients given high emetogenic chemotherapy (HEC): As standard of care for nausea and vomiting after high emetogenic chemotherapy (HEC), subjects will receive fosaprepitant 150 mg IV once, palonosetron 0.25 mg IV once, dexamethasone 12 mg oral or IV once on day 1. Patients will be randomly assigned to either the DEX group to receive dexamethasone or to the OLA group to receive olanzapine for the first cycle of chemotherapy. DEX group: dexamethasone (Decadron) 8 mg oral daily on days 2-4. OLA group: olanzapine (Zyprexa)10 mg oral each night on days 1-4. For the second cycle of chemotherapy, the subject will switch to the other group. For future cycles of chemotherapy, the subject will choose the drug that worked best. For patients give moderate emetogenic chemotherapy (MEC): As standard of care for nausea and vomiting after moderate emetogenic chemotherapy (MEC), subjects will receive granisetron 2 mg oral once and, dexamethasone 12 mg oral once on day 1. Subjects will be randomly assigned to either the DEX group to receive dexamethasone or to the OLA group to receive olanzapine for the first cycle of chemotherapy. DEX group: dexamethasone (Decadron) 8 mg oral daily on days 2-3. OLA group: olanzapine (Zyprexa)10 mg oral each night on days 1-3. For the second cycle of chemotherapy, the subject will switch to the other group. For future cycles of chemotherapy, the subject will choose the drug that worked best. Subjects (both HEC and MEC) will be asked to complete a survey prior to treatment on Day 1 of cycle 1 and cycle 2 prior to treatment. On Day 2 and Day 6 a member of the study will contact subjects by phone to complete another survey on any symptoms you may be experiencing.

Official Title
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The Efficacy of Steroid-Sparing Anti-Emetic Therapy in Patients Treated With High or Moderate Emetogenic Chemotherapy; Single Center Non-Inferiority Open Label Randomized Controlled Trial

Conditions
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Chemotherapy-induced Nausea and Vomiting

Intervention / Treatment
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* Drug: OLA group: Olanzapine
* Drug: DEX group: Dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years and older confirmed cancer diagnosis starting cycle 1 of an FDA approved treatment that is categorized as high-emetogenic (nausea and vomiting inducing) chemotherapy per National Comprehensive Cancer Network® guidelines Eastern Cooperative Oncology Group performance score of 0 or 1 appropriate renal function appropriate hepatic function appropriate hematologic function. Exclusion Criteria: Patients will be excluded if they experience nausea or vomiting up to 24 hours before chemotherapy, currently on a glucocorticoid therapy contraindication to glucocorticoid therapy taking any medication that has antiemetic properties. scheduled or planned to receive radiation within one week of or concurrently with chemotherapy brain metastases.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Subjects will be randomly assigned to either the DEX group to receive dexamethasone or to the OLA group to receive olanzapine for the first cycle of chemotherapy. DEX group: dexamethasone (Decadron) 8 mg oral daily on days 2-4 after HEC (days 2-3 after MEC). OLA group: olanzapine (Zyprexa)10 mg oral each night on days 1-4 after HEC (days 2-3 after MEC). For the second cycle of chemotherapy, the subject will switch to the other group. Groups: OLA then DEX; DEX then OLA
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OLA then crossover to DEX<br>OLA group: olanzapine (Zyprexa) 10 mg oral each night after chemotherapy cycle 1 on days 1-4 after HEC (or days 1-3 after MEC). DEX group: dexamethasone (Decadron) 8 mg oral daily after chemotherapy cycle 2 on days 2-4 after HEC (or days 2-3 after MEC) | Drug: OLA group: Olanzapine<br>* OLA group: olanzapine 10 mg oral each night on days 1-4 after HEC (or days 1-3 after MEC). DEX group: dexamethasone (Decadron) 8 mg oral daily on days 2-4 after HEC (or days 2-3 after MEC).<br>* Other names: Steroid-sparing therapy;Drug: DEX group: Dexamethasone<br>* DEX group: dexamethasone (Decadron) 8 mg oral daily on days 2-4 after HEC (or days 2-3 after MEC).. OLA group: olanzapine 10 mg oral each night on days 1-4 after HEC (or days 1-3 after MEC).<br>* Other names: Steroid therapy;|
| Active Comparator: DEX then crossover to OLA<br>DEX group: dexamethasone (Decadron) 8 mg oral daily after chemotherapy cycle 1 on days 2-4 after HEC (or days 2-3 after MEC) OLA group: olanzapine (Zyprexa) 10 mg oral each night after chemotherapy cycle 2 on days 1-4 after HEC (or days 1-3 after MEC). | Drug: OLA group: Olanzapine<br>* OLA group: olanzapine 10 mg oral each night on days 1-4 after HEC (or days 1-3 after MEC). DEX group: dexamethasone (Decadron) 8 mg oral daily on days 2-4 after HEC (or days 2-3 after MEC).<br>* Other names: Steroid-sparing therapy;Drug: DEX group: Dexamethasone<br>* DEX group: dexamethasone (Decadron) 8 mg oral daily on days 2-4 after HEC (or days 2-3 after MEC).. OLA group: olanzapine 10 mg oral each night on days 1-4 after HEC (or days 1-3 after MEC).<br>* Other names: Steroid therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response (CR) over 120 hours following chemotherapy | Complete response (CR) over 120 hours following chemotherapy, where CR is the absence of emesis and no use of a rescue antiemetic medication, in the acute phase (<24 hours following chemotherapy), delayed phase (≥24 hours but ≤120 hours following chemotherapy) and overall (≤ 120 hours following chemotherapy). | 120 hours following chemotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete control (CC- no emesis, no rescue medication and no more than minimal nausea) | no emesis, no rescue medication and no more than minimal nausea | 120 hours following chemotherapy | 
| Total Control (TC- no emesis, no rescue medication, no nausea) | no emesis, no rescue medication, no nausea | 120 hours following chemotherapy | 
| Severity of nausea and vomiting self-reported by patient questionnaire | None, mild or greater than mild | 120 hours after chemotherapy | 
| medication side effects | medication side effects including sedation, insomnia, agitation, indigestion/heartburn, depression, anorexia, increased appetite/hunger and rash/acne | 120 hours after chemotherapy |