An Efficacy and Safety Study of Intravenous Palonosetron Administered as an Infusion and as a Bolus for the Prevention of Nausea and Vomiting

Study Overview
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Brief Summary
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PALO-15-17 is a clinical study assessing efficacy and safety of a single dose of palonosetron 0.25 mg administered as a 30-minute IV infusion compared to palonosetron 0.25 mg administered as a 30-second IV bolus (Aloxi, an antiemetic drug), both given with oral dexamethasone. The objective of the study is to demonstrate that infused IV palonosetron 0.25 mg is as effective as (non-inferior to) injected palonosetron IV 0.25 mg to prevent nausea and vomiting induced by highly emetogenic cancer chemotherapy in the 0-24 hours after administration of a single cycle of highly emetogenic chemotherapy

Official Title
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A Phase 3, Single-dose, Multicenter, Randomized, Double-blind, Parallel Group Study to Assess the Efficacy and Safety of Palonosetron 0.25 mg Administered as a 30-minute IV Infusion Compared to Palonosetron 0.25 mg Administered as a 30-second IV Bolus for the Prevention of Chemotherapy-induced Nausea and Vomiting in Cancer Patients Receiving Highly Emetogenic Chemotherapy.

Conditions
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Chemotherapy-Induced Nausea and Vomiting

Intervention / Treatment
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* Drug: Palonosetron
* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written informed consent Histologically or cytologically confirmed solid tumor malignancy. Naïve to cytotoxic chemotherapy. Previous biological or hormonal therapy will be permitted. Scheduled to receive first course of one of the following reference HEC, alone or in combination with other chemotherapeutic agents on Day 1: cisplatin administered as a single IV dose of ≥ 70 mg/m2 cyclophosphamide ≥1500 mg/m2 carmustine (BCNU) >250 mg/m2 dacarbazine (DTIC) mechloretamine (nitrogen mustard) Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2 . If a patient is female, she shall be of non-childbearing potential or of childbearing potential using reliable contraceptive measures and having a negative urine pregnancy test. Hematologic and metabolic status adequate for receiving an highly emetogenic regimen based on laboratory criteria (Total Neutrophils,Platelets, Bilirubin, Liver enzymes, Serum Creatinine or Creatinine Clearance) Able to read, understand, follow the study procedure and complete patient diary. Exclusion Criteria: Lactating woman. Current use of illicit drugs or current evidence of alcohol abuse. Scheduled to receive moderately emetogenic chemotherapy or highly emetogenic chemotherapy from Day 2 to Day 5. Received or is scheduled to receive radiation therapy to the abdomen or the pelvis within 1 week prior to the start of the reference HEC administration on Day 1 or between Days 1 to 5. Any vomiting, retching, or nausea (grade ≥ 1 as defined by National Cancer Institute) within 24 hours prior to the start of the reference HEC administration on Day 1. Symptomatic primary or metastatic CNS malignancy. Active peptic ulcer disease, gastrointestinal obstruction, increased intracranial pressure, hypercalcemia, an active infection or any illness or medical conditions (other than malignancy) that, in the opinion of the Investigator, may confound the results of the study, represent another potential etiology for emesis and nausea (other than chemotherapy-induced nausea and vomiting) or pose unwarranted risks in administering the study drugs to the patient. Known hypersensitivity or contraindication to 5-HT3 receptor antagonists Known contraindication to the IV administration of 50 mL 5% glucose solution. Participation in a previous clinical trial involving palonosetron. Any investigational drugs (other than those given in this study) taken within 4 weeks prior to Day 1, and/or is scheduled to receive any investigational drug during the present study. Systemic corticosteroid therapy at any dose within 72 hours prior to the start of the reference HEC administration on Day 1. However, topical and inhaled corticosteroids are permitted. Scheduled to receive bone marrow transplantation and/or stem cell rescue therapy. Any medication with known or potential antiemetic activity within 24 hours prior to the start of the reference HEC administration on Day 1, including but not limited to 5-HT3 receptor antagonists and NK-1 receptor antagonists Concurrent medical condition that would preclude administration of dexamethasone for 4 days such as systemic fungal infection or uncontrolled diabetes.

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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: I.V. palonosetron infusion plus dexamethasone<br>Intravenous palonosetron (Aloxi 0.25 mg solution for injection) as an infusion with oral dexamethasone, both given on Day 1, prior to the scheduled start of cisplatin; then dexamethasone from Days 2 through 4. | Drug: Palonosetron<br> <br> Drug: Dexamethasone<br> <br> |
| Active Comparator: I.V. palonosetron bolus plus dexamethasone<br>Intravenous palonosetron (Aloxi 0.25 mg solution for injection) as a bolus with oral dexamethasone, both given on Day 1, prior to the scheduled start of cisplatin; then dexamethasone from Days 2 through 4. | Drug: Palonosetron<br> <br> Drug: Dexamethasone<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With Complete Response (CR) Defined as no Emesis, no Rescue Medication, in the Acute Phase |  | 0-24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With Complete Response (CR) Defined as no Emesis, no Rescue Medication, in the Delayed Phase |  | >24-120 hours | 
| Percentage of Patients With Complete Response (CR) Defined as no Emesis, no Rescue Medication, in the Overall Phase |  | 0-120 hours | 
| Percentage of Patients With no Emetic Episodes in the Acute Phase |  | 0-24 hours | 
| Percentage of Patients With no Emetic Episodes in the Delayed Phase |  | >24-120 hours | 
| Percentage of Patients With no Emetic Episodes in the Overall Phase |  | 0-120 hours | 
| Percentage of Patients With no Rescue Medication in the Acute Phase |  | 0-24 hours | 
| Percentage of Patients With no Rescue Medication in the Delayed Phase |  | >24-120 hours | 
| Percentage of Patients With no Rescue Medication in the Overall Phase |  | 0-120 hours |