Buccal Film Versus IV Injection Palonosetron for Moderately Emetogenic Chemotherapy Induced Nausea and Vomiting

• ClinicalTrials.gov Identifier: NCT04592198
• Recruitment Status: Completed
• First Posted: October 19, 2020
• Last Update Posted: May 14, 2021
• Sponsor: Xiamen LP Pharmaceutical Co., Ltd
• Information provided by (Responsible Party): Xiamen LP Pharmaceutical Co., Ltd

Study Description

Brief Summary:

Phase 2 study to compare efficacy, safety and PK of palonosetron, a long acting 5-HT3 receptor antagonist, by buccal film delivery compared to iv injection for chemotherapy induced nausea or vomiting (CINV). Subjects receive a single dose of palonosetron prior to moderately emetogenic chemotherapy.

Condition or disease	Intervention/treatment	Phase
Nausea With Vomiting Chemotherapy-Induced	Drug: Palonosetron Hydrochloride Buccal Film 0.25 Mg; Drug: Palonosetron Hydrochloride Buccal Film 0.5 Mg; Drug: Palonosetron Hydrochloride, 0.25 Mg/5 mL Intravenous Solution	Phase 2

Detailed Description:

This is a Phase 2 study to compare efficacy, safety and PK of palonosetron, a long acting 5-HT3 receptor antagonist, by buccal film compared to iv injection for moderately emetogenic chemotherapy-induced nausea or vomiting (CINV) in cancer patients. Subjects are randomized into three treatment groups, two with the experimental study drug palonosetron in buccal film at one of two different doses or the control treatment using Palonosetron hydrochloride iv injection. Palonosetron PK will be assessed in a subgroup of each treatment group.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 22 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Randomized, Dose-ranging, Open-label, Parallel Group Study to Assess the Efficacy, Safety and Pharmacokinetics of Palonosetron HCl Buccal Film Versus IV Palonosetron 0.25 mg (ALOXI®) for the Prevention of Chemotherapy-induced Nausea and
• Actual Study Start Date: October 1, 2020
• Actual Primary Completion Date: March 26, 2021
• Actual Study Completion Date: March 26, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: A (Buccal 0.25 Mg); Palonosetron HCl Buccal Film 0.25 Mg and oral dexamethasone 12 Mg, both administered on Day 1, and dexamethasone 8 Mg PO on days 2 and 3	Drug: Palonosetron Hydrochloride Buccal Film 0.25 Mg; Dose equal to the iv control; Other Name: Buccal Film Low Dose
Experimental: B (Buccal 0.5 Mg); Palonosetron HCl Buccal Film 0.5 Mg and oral dexamethasone 12 Mg, both administered on Day 1, and dexamethasone 8 Mg PO on days 2 and 3	Drug: Palonosetron Hydrochloride Buccal Film 0.5 Mg; Dose twice that of iv control; Other Name: Buccal Film High dose
Active Comparator: C (IV Injection 0.25 Mg); IV palonosetron 0.25 Mg (ALOXI®) and oral dexamethasone 12 Mg, both administered on Day 1, and dexamethasone 8 Mg PO on days 2 and 3	Drug: Palonosetron Hydrochloride, 0.25 Mg/5 mL Intravenous Solution; iv control; Other Name: Control Standard Treatment (Aloxi)

Outcome Measures

Primary Outcome Measures :

1. Complete acute response [ Time Frame: during the first 24 hours after chemotherapy ]
   no emetic episode and no rescue medication

Secondary Outcome Measures :

1. Complete delayed response [ Time Frame: 24-120 hours post chemotherapy ]
   no emetic episode and no rescue medication
2. Complete response [ Time Frame: up to 120 hours post chemotherapy ]
   no emetic episode and no rescue medication
3. No nausea [ Time Frame: up to 120 hours post chemotherapy ]
   visual analog scale (0-100 mm, 0=no, 100=severe) < 5 mm
4. No significant nausea [ Time Frame: up to 120 hours post chemotherapy ]
   visual analog scale (0-100 mm, 0=no, 100=severe) < 25 mm
5. Complete protection [ Time Frame: up to 120 hours post chemotherapy ]
   no emesis, no rescue therapy, no significant nausea (questionnaire)
6. Number of emetic episodes [ Time Frame: up to 120 hours post chemotherapy ]
   Number of emetic episodes
7. Time to rescue medication [ Time Frame: up to 120 hours post chemotherapy ]
   Time to rescue medication
8. Time to treatment failure [ Time Frame: up to 120 hours post chemotherapy ]
   time to first emetic episode or administration of rescue therapy, whichever occurred first
9. Severity of nausea [ Time Frame: up to 120 hours post chemotherapy ]
   Rhodes Index of Nausea, Vomiting and Retching (0-4, 0=no nausea, 4=severe nausea)
10. Subject global satisfaction with therapy [ Time Frame: up to 120 hours post chemotherapy ]
    visual analog scale (0-100mm, 0=not at all satisfied, 100=totally satisfied)
11. Quality of life questionnaire [ Time Frame: up to 120 hours post chemotherapy ]
    Functional Living Index-Emesis

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• With histologically or cytologically confirmed malignant disease;

  • Karnofsky index ≥ 50;
  • Be scheduled to receive the first course of MEC to be administered on Day 1
• Using reliable contraceptive measures;
• negative serum pregnancy test (if potentially child bearing)
• Be able to read, understand, and follow the study procedures and able to complete patient diary autonomously.

Exclusion Criteria:

• Expect to be non-compliant with the study procedures;
• Received investigational drugs within 30 days before the start of study treatment or scheduled to receive a highly or moderately emetogenic chemotherapeutic agent during Day 2 to 6 of the study;
• Has any condition that could have been associated with a risk of emesis near or at the time of study drug administration;
• Have a clinically unstable seizure disorder with seizure activity requiring anticonvulsant medication;
• Experienced any vomiting, retching, or National Cancer Institute (NCI) Common Toxicity Criteria grade 2 or 3 or nausea within 24 hours preceding chemotherapy;
• Have ongoing nausea or vomiting from any organic etiology;
• Have severe renal or hepatic impairment;
• Have positive serology test results;
• Have a known contraindication to 5-HT3 receptor antagonists;
• Treated with commercially available or investigative palonosetron formulation within 2 weeks prior to start of study treatment;
• Allergic to palonosetron or any other 5-HT3 antagonist;
• Currently a user of any recreational or illicit drugs (including marijuana) or has current evidence of drug or alcohol abuse or dependence as determined by the investigator;
• Will be receiving stem cell rescue therapy in conjunction with study related course of emetogenic chemotherapy;
• Received or will receive total body irradiation or radiation therapy to the abdomen or pelvis in the week prior to Treatment Day 1 and/or during the diary reporting period.
• Had non-chronic benzodiazepine, opioid or opioid like (e.g., tramadol hydrochloride) therapy initiated within 48 hours prior to study drug administration or is expected to receive within 120 hours following initiation of chemotherapy, except for single daily doses of midazolam, temazepam or triazolam.
• Started on systemic corticosteroid therapy within 72 hours prior to study drug administration or is expected to receive a corticosteroid as part of chemotherapy regimen.

Contacts and Locations

Locations

United States, California

Pacific Cancer Medical Center, Inc.

Anaheim, California, United States, 92801

United States, Florida

Ocala Oncology Center PL DBA Florida Cancer Affiliates

Ocala, Florida, United States, 34474

United States, Illinois

Edward H. Kaplan MD & Associates

Skokie, Illinois, United States, 60076

United States, Mississippi

Hattiesburg Clinic Hematology/Oncology

Hattiesburg, Mississippi, United States, 39401

United States, Pennsylvania

Gettysburg Cancer Center

Gettysburg, Pennsylvania, United States, 17325

Monongahela Valley Hospital/ Regional Cancer Center

Monongahela, Pennsylvania, United States, 15063

United States, South Carolina

Charleston Oncology

Charleston, South Carolina, United States, 29406

Sponsors and Collaborators

Xiamen LP Pharmaceutical Co., Ltd

More Information

• Responsible Party: Xiamen LP Pharmaceutical Co., Ltd
• ClinicalTrials.gov Identifier: NCT04592198
• Other Study ID Numbers: LP-CT-PALO-202002
• First Posted: October 19, 2020
• Last Update Posted: May 14, 2021
• Last Verified: May 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Nausea; Vomiting; Signs and Symptoms, Digestive; Palonosetron; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Serotonin 5-HT3 Receptor Antagonists; Serotonin Antagonists; Serotonin Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action