Buccal Film vs IV Palonosetron for Prevention of CINV in Cancer Patients Receiving MEC

Study Overview
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Brief Summary
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The phase 3 study is to compare the efficacy and safety of palonosetron, a long-acting 5-HT3 receptor antagonist, by buccal film delivery compared to IV injection for the prevention of chemotherapy-induced nausea and vomiting. Subjects receive a single dose of palonosetron prior to moderately emetogenic chemotherapy.

Detailed Description
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This is a phase 3 randomized, double-blind, parallel group study designed to evaluate the efficacy and safety of palonosetron HCL buccal film versus IV palonosetron for the prevention of chemotherapy-induced nausea and vomiting in cancer patients receiving moderately emetogenic chemotherapy (MEC). Subjects are randomized into two treatment groups, one with the experimental study drug palonosetron in buccal film, the other one with the control treatment using Palonosetron hydrochloride IV injection. Palonosetron PK will be assessed in a subgroup of each treatment group (two sample points, 10% of subjects).

Official Title
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Efficacy and Safety of Palonosetron HCl Buccal Film Versus IV Palonosetron for Prevention of Chemotherapy-induced Nausea and Vomiting in Cancer Patients Receiving Moderately Emetogenic Chemotherapy

Conditions
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Chemotherapy-induced Nausea and Vomiting

Intervention / Treatment
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* Drug: Palonosetron HCl Buccal Film 0.5 mg
* Drug: IV Palonosetron 0.25 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, at least 18-years of age; Provide written informed consent; Chemotherapy naïve subject with histologically or cytologically confirmed malignant disease; or chemotherapy non-naïve subject with histologically proven diagnosis of cancer; Karnofsky index ≥ 50; Be scheduled to receive MEC to be administered on Day 1; Exclusion Criteria: Unable to understand or cooperate with study procedure； Received any investigational drug 30 days prior to study entry； Used any drug with anti-emetic efficacy 24 hours prior to treatment and during the study； Enrollment in a previous study with palonosetron； Seizure disorder requiring anticonvulsant medication; Experienced any vomiting, retching, or NCI Common Toxicity Criteria grade 2 or 3 nausea in the 24 hours preceding chemotherapy； Ongoing vomiting from any organic etiology； Experienced nausea (moderate to severe or vomiting following any previous chemotherapy)； Scheduled to receive moderately or highly-emetogenic chemotherapy or radiotherapy during the study； Known contraindication to 5-HT3 antagonist or dexamethasone； Scheduled to receive bone marrow or stem cell transplant during study; Symptomatic primary or metastatic CNS malignancy; Lactating female.

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: Palonosetron HCl Buccal Film<br>Palonosetron HCl Buccal Film 0.5 mg 1 hr before administration of moderately emetogenic chemotherapy and normal saline injection 30 minutes before administration of moderately emetogenic chemotherapy | Drug: Palonosetron HCl Buccal Film 0.5 mg<br>* Palonosetron HCl Buccal Film and IV palonosetron placebo, both administered on Day 1<br>|
| Active Comparator: Palonosetron IV Injection<br>Placebo buccal film 1 har before administration of moderately emetogenic chemotherapy and Palonosetron HCl Injection 0.25 mg 30 min before administration of moderately emetogenic chemotherapy | Drug: IV Palonosetron 0.25 mg<br>* IV Palonosetron and Palonosetron HCl Buccal Film placebo, both administered on Day 1<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response | No emetic episode and no rescue medication | During the first 24 hours after chemotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response | No emetic episode and no rescue medication | 24-120 hours post chemotherapy | 
| Absence of nausea | Absence of nausea based on daily patient questionnaire (yes or no) and no emetic episode or rescue medication | up to 24 hours post chemotherapy, 24-120 hours post chemotherapy, and up to 120 hours post chemotherapy | 
| Complete response | The proportion of patients with complete response | up to 120 hours after chemotherapy | 
| Complete control | The proportion of patients with complete control | up to 24 hours post chemotherapy, 24-120 hours post chemotherapy, and up to 120 hours post chemotherapy | 
| Number of emetic episodes | Number of emetic episodes | up to 120 hours after chemotherapy |