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

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.

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

Study Overview

• Status: Completed
• Conditions: Chemotherapy-Induced Nausea and Vomiting
• Intervention / Treatment: Drug: Dexamethasone; Drug: Palonosetron

• Study Type: Interventional
• Enrollment (Actual): 441
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belarus
  • Lesnoy, Belarus, 223052
    • N.N. Aleksandrov Republican Research Oncology and Medical Radiology Center, Department of Chemotherapy
  • Minsk, Belarus, 220013
    • Minsk City Clinical Oncology Center
• Bosnia and Herzegovina
  • Banja Luka, Bosnia and Herzegovina
    • University Clinical Centre of the Republic of Srpska
• Bulgaria
  • Dobrich, Bulgaria, 9300
    • Multiprofile Hospital for Active Treatment, Dobrich, Department of Medical Oncology
  • Haskovo, Bulgaria, 6300
    • Specialized Hospital for Active Treatment in Oncology, Haskovo, Department of Medical Oncology
  • Plovdiv, Bulgaria, 4002
    • Multiprofile Hospital for Active Treatment "Central Onco Hospital", Plovdiv, Department of Medical Oncology
  • Rousse, Bulgaria, 7002
    • Complex Oncology Center, Ruse, Department of Medical Oncology
  • Sofia, Bulgaria, 1303
    • Multiprofile Hospital for Active Treatment "Serdika", Sofia, Department of Medical Oncology
  • Sofia, Bulgaria, 1431
    • University Multiprofile Hospital for Active Treatment "Sveti Ivan Rilski", Sofia, Department of Medical Oncology
  • Sofia, Bulgaria
    • Multiprofile Hospital for Active Treatment for Wonen's Health "Nadezhda"
  • Varna, Bulgaria, 9010
    • Hospital for Active Treatment of Oncological Diseases "Dr. Marko Antonov Markov", Varna, Department of Medicinal Oncology and Palliative Care
  • Varna, Bulgaria, 9010
    • Multiprofile Hospital for Active Treatment "Sveta Marina", Varna, Clinic of Medical Oncology
• Georgia
  • Tbilisi, Georgia, 0159
    • LTD Institute of Clinical Oncology
  • Tbilisi, Georgia, 0160
    • Ltd Aversi Clinic
  • Tbilisi, Georgia, 0131
    • JSC NeoMedi
  • Tbilisi, Georgia
    • LDT High Technology Medical Center University Clinic
• Greece
  • Athens, Greece
    • "Sotiria" Chest Diseases Hospital of Athens
  • Thessaloniki, Greece, 570 01
    • Thermi Clinic S.A.
  • Thessaloniki, Greece, 570 10
    • General Hospital of Thessaloniki "G. Papanikolaou", University Department of Pulmonology
  • Thessaloniki, Greece
    • Bioclinic Thessalonikis S.A.
• Hungary
  • Budapest, Hungary, 1121
    • Koranyi National Institute of TBC and Pulmonology
  • Budapest, Hungary, 1145
    • Uzsoki Hospital, Department of Radiation Oncology
  • Debrecen, Hungary
    • University of Debrecen, Medical and Health Science Center
  • Gyor, Hungary, 9024
    • Petz Aladar County Teaching Hospital, Center for Oncoradiology
  • Kaposvár, Hungary, 7400
    • Kaposi Mor Teaching Hospital, Centre for Clinical Oncology
  • Miskolc, Hungary, 3526
    • Borsod-Abauj-Zemplen County Hospital and University Educational Hospital
  • Nyíregyháza, Hungary
    • Szabolcs-Szatmar-Bereg County Hospitals and University Teaching Hospital
  • Pecs, Hungary
    • Medical Center of the University of Pecs
• Lithuania
  • Kaunas, Lithuania, 45434
    • Hospital of Lithuanian University of Health Sciences Kaunas Clinics, Oncology Hospital, Department of Conservative Oncology
  • Kaunas, Lithuania, 50009
    • Hospital of Lithuanian University of Health Sciences Kaunas Clinics, Clinic of Oncology and Hematology
• Romania
  • Baia Mare, Romania
    • Oncopremium Team SRL, Department of Oncology
  • Bucharest, Romania, 022328
    • Prof. Dr. Alexandru Trestioreanu Institute of Oncology, Medical Oncology Department II
  • Bucharest, Romania, 030171
    • Coltea Clinical Hospital, Department of Medical Oncology
  • Bucharest, Romania, 031864
    • Hifu Terramed Conformal SRL, Department of Medical Oncology
  • Bucharest, Romania
    • Ianuli Med Consult SRL, Oncology Department
  • Cluj-Napoca, Romania, 400015
    • "Prof. Dr. Ion Chiricuta" Institute of Oncology, Radiotherapy Department I
  • Cluj-Napoca, Romania
    • Radiotherapy Center Cluj SRL, Department of Oncology
  • Constanta, Romania, 900591
    • Constanta Emergency Clinical County Hospital, Department of Medical Oncology
  • Craiova, Romania
    • Oncology Center "Sf. Nectarie", Department of Medical Oncology
  • Suceava, Romania, 720237
    • Suceava Sf. Ioan cel Nou Emergency County Hospital, Department of Medical Oncology
  • Timisoara, Romania, 300239
    • Oncomed SRL, Department of Medical Oncology
  • Timisoara, Romania
    • Oncocenter Clinical Oncology SRL, Department of Medical Oncology
• Russian Federation
  • Arkhangelsk, Russian Federation
    • Arkhangelsk Clinical Oncology Center
  • Barnaul, Russian Federation
    • Altay Territorial Oncology Center
  • Bryansk, Russian Federation
    • Bryansk Regional Oncology Center
  • Chelyabinsk, Russian Federation
    • Evimed, LLC
  • Chelyabinsk, Russian Federation
    • Chelyabinsk Regional Clinical Oncology Center
  • Ekaterinburg, Russian Federation
    • Sverdlovsk Regional Oncology Center
  • Ivanovo, Russian Federation
    • Ivanovo Regional Oncology Center
  • Kaluga, Russian Federation
    • Kaluga Regional Oncology Center
  • Kazan, Russian Federation
    • Republican Clinical Oncology Center
  • Krasnoyarsk, Russian Federation
    • Krasnoyarsk A.I. Kryzhanovsky Regional Oncology Center
  • Moscow, Russian Federation
    • Moscow City Oncology Hospital #62
  • Moscow, Russian Federation
    • Moscow Clinical Scientific and Practical Center
  • Moscow, Russian Federation
    • N.N. Blokhin Russian Oncology Research Center, Surgery Dept. 2
  • Moscow, Russian Federation
    • N.N. Blokhin Russian Oncology Research Center, Surgery Dept. of Female Reproductive System Tumors
  • Moscow, Russian Federation
    • N.N. Blokhin Russian Oncology Research Center
  • Nizhny Novgorod, Russian Federation
    • Branch #1 of Nizhny Novgorod Regional Oncology Center
  • Novosibirsk, Russian Federation
    • City Clinical Hospital #1
  • Novosibirsk, Russian Federation
    • Novosibirsk Regional Oncology Center
  • Omsk, Russian Federation
    • Clinical Oncology Center
  • Omsk, Russian Federation
    • Clinical Oncology Center, Dept. of Chemotherapy
  • Orenburg, Russian Federation
    • Orenburg Regional Clinical Oncology Center
  • Pyatigorsk, Russian Federation
    • Pyatigorsk Oncology Center
  • Ryazan, Russian Federation
    • Regional Clinical Oncology Center
  • Samara, Russian Federation
    • Samara Regional Clinical Oncology Center
  • St. Petersburg, Russian Federation
    • First I.P. Pavlov State Medical University of St. Petersburg
  • St. Petersburg, Russian Federation
    • City Clinical Oncology Center, Thoracic Oncology Dept.
  • St. Petersburg, Russian Federation
    • City Clinical Oncology Center, Urology Oncology Dept.
  • St. Petersburg, Russian Federation
    • City Clinical Oncology Center
  • St. Petersburg, Russian Federation
    • St.Petersburg Municipal Clinical Oncology Center
  • Tambov, Russian Federation
    • Tambov Regional Oncology Center
  • Tomsk, Russian Federation
    • Tomsk Research Institute of Oncology, General Oncology Dept.
  • Tomsk, Russian Federation
    • Tomsk Research Institute of Oncology
  • Ufa, Russian Federation
    • Republican Clinical Oncology Center
  • Veliky Novgorod, Russian Federation
    • Regional Clinical Oncology Center

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: I.V. palonosetron infusion plus dexamethasone; 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: Dexamethasone; Drug: Palonosetron
Active Comparator: I.V. palonosetron bolus plus dexamethasone; 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: Dexamethasone; Drug: Palonosetron

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Helsinn Healthcare SA
• Collaborators: PSI CRO

Study record dates

Study Major Dates

• Study Start: October 1, 2015
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: September 21, 2015
• First Submitted That Met QC Criteria: September 21, 2015
• First Posted (Estimate): September 22, 2015

Study Record Updates

• Last Update Posted (Actual): June 20, 2018
• Last Update Submitted That Met QC Criteria: June 18, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Nausea; Vomiting; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Serotonin Agents; Serotonin Antagonists; Serotonin 5-HT3 Receptor Antagonists; Dexamethasone; Palonosetron
• Other Study ID Numbers: PALO-15-17