Ondansetron Versus Palonosetron Antiemetic Regimen Prior to Highly Emetogenic Chemotherapy(HEC)

Study Overview
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Brief Summary
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Palonosetron is different from ondansetron because it stays in the body longer and may prevent nausea and vomiting for a longer period of time than ondansetron. It is standard practice to use dexamethasone and aprepitant with either ondansetron or palonosetron to prevent nausea and vomiting caused by highly emetogenic chemotherapy. Although these combinations are commonly used, they have never been compared to each other. The purpose of this study is to record the amount of nausea and vomiting, and the amount of rescue medication that is used with these two different anti-emetic regimens

Detailed Description
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PRIMARY OBJECTIVES: I. The goal of this study is to evaluate the overall complete response rate (CR, no emesis and no use of rescue medication from 0 to 120 hours after chemotherapy) of two different antiemetic regimens (palonosetron + aprepitant + dexamethasone and ondansetron + aprepitant + dexamethasone) for patients undergoing the first cycle of highly emetogenic chemotherapy (HEC). OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive palonosetron hydrochloride intravenously (IV) 30 minutes prior to chemotherapy on day 1, aprepitant orally (PO) 60 minutes prior to chemotherapy on days 1-3, and dexamethasone PO 30 minutes prior to chemotherapy on days 1-4. ARM II: Patients receive ondansetron PO 30 minutes prior to chemotherapy on day 1 and aprepitant and dexamethasone as in Arm I. After completion of study treatment, patients are followed up for 7 days.

Official Title
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Pilot Study on the Efficacy of an Ondansetron Versus Palonosetron-containing Antiemetic Regimen Prior to Highly Emetogenic Chemotherapy(HEC).

Conditions
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Malignant Neoplasm

Intervention / Treatment
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* Drug: aprepitant
* Drug: palonosetron hydrochloride
* Drug: ondansetron
* Drug: dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed malignancy Chemotherapy naive or treated with only low or minimally emetogenic chemotherapy in the past (as defined by the National Comprehensive Cancer Network version [v].2.201 Antiemetic Guidelines) Scheduled to receive the first dose of their first cycle of HEC Patients receiving multi-day chemotherapy, the HEC portion must be on day 1 and the remaining days of chemotherapy must be minimally emetogenic (i.e. fluorouracil) Performance status of Eastern Cooperative Oncology Group (ECOG) grade 0-2 Able to provide informed consent Able to read and write in English or have someone that can that can translate to them and record their diary entries Able to take oral medications Patients are allowed to participate in a concurrent clinical trial, if the other trial: Does not mandate an antiemetic regimen that interferes with this study Allows antiemetic administration at the physician's discretion Does not prohibit the patient from participating in this study Patients must be willing to participate with daily diary entries for 5 days following chemotherapy, and agree to have a 5 minute follow-up call on day 2 or 3 and day 5, 6 or 7 Exclusion Criteria: Has stage IV (metastatic) disease Known hypersensitivity to ondansetron, palonosetron, aprepitant, or dexamethasone Have received or will receive agents that are strong cytochrome P450 3A4 (CYP450 3A4) inducers and/or inhibitors and known to cause clinically relevant drug interactions within one week prior to study treatment and continuing through day 5; any vomiting or retching within 24 hours before administration of chemotherapy Grade 2 nausea or greater, according to the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v 4.0) within 24 hours before administration of chemotherapy Received an antiemetic within 24 hours before study drug administration, excluding the use of benzodiazepines Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 2.5 times upper limit of normal Total bilirubin > 1.5 times upper limit of normal

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 88 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (palonosetron hydrochloride)<br>Patients receive palonosetron hydrochloride IV 30 minutes prior to chemotherapy on day 1, aprepitant PO (by mouth) 60 minutes prior to chemotherapy on days 1-3, and dexamethasone PO 30 minutes prior to chemotherapy on days 1-4. | Drug: aprepitant<br>* Given by mouth<br>* Other names: ONO-7436;Drug: palonosetron hydrochloride<br>* Given IV(intervenous infusion)<br>* Other names: RS 25259-197;Drug: dexamethasone<br>* Given PO<br>* Other names: DXM;|
| Experimental: Arm II (ondansetron)<br>Patients receive ondansetron PO 30 minutes prior to chemotherapy on day 1 and aprepitant and dexamethasone as in Arm I. | Drug: aprepitant<br>* Given by mouth<br>* Other names: ONO-7436;Drug: ondansetron<br>* Given PO<br>* Other names: Zofran;Drug: dexamethasone<br>* Given PO<br>* Other names: DXM;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall CR(Complete Response)After the First Course of HEC, Defined as no Emesis and no Use of Rescue Medication | We will use exact binomial methods to estimate proportions and their associated 95% confidence intervals. | Up to 120 hours after completion of chemotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute CR (Complete Response) | After the First Course of HEC, Defined as no Emesis and no Use of Rescue Medication from time 0 to 24 hours. | 0-24 hours after chemotherapy | 
| Delayed CR (Complete Response) | After the First Course of HEC, Defined as no Emesis and no Use of Rescue Medication From Time 24to 120 Hours. | 24-120 hours after chemotherapy | 
| Percentage of Patients Who Experienced Grade 1, 2 or 3 Nausea From Time 0 to 120 Hours | The percentage of patients who experienced grade 1, 2 or 3 nausea from time 0 to 120 hours. Nausea graded using the National Cancer Institute (NCI) CTCAE (Common Toxicity Criteria for Adverse Effects)version 4.0 Nausea Grading Scale. Grade 1=Loss of appetite without alteration in eating habits, Grade 2= Oral intake decreased without significant weight loss, dehydration or malnutrition, Grade 3= Inadequate oral caloric or fluid intake; tube feeding, TPN, or hospitalization indicated. | Time 0 to 120 hours | 
| Visual Analog Scale (VAS) Scores |  | Up to 7 days after completion of study treatment | 
| Use of Rescue Medication for Each Treatment Arm |  | From time 0 to 120 hours | 
| Percentage of Patients Who Experienced Grade 1, 2 or 3 Vomiting From Time 0 to 120 Hours | The percentage of patients who experienced grade 1, 2 or 3 vomiting from time 0 to 120 hours. Nausea graded using the National Cancer Institute (NCI) CTCAE v 4.0 vomiting Grading Scale. Grade 1=Loss of appetite without alteration in eating habits, Grade 2= Oral intake decreased without significant weight loss, dehydration or malnutrition, Grade 3= Inadequate oral caloric or fluid intake; tube feeding, TPN, or hospitalization indicated. | From time 0 to 120 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HEC, ondansetron, palonosetron, emetogenic chemotherapy