A Safety Study of Intravenous Pro-Netupitant and Palonosetron Combination for the Prevention of Nausea and Vomiting

June 18, 2018 updated by: Helsinn Healthcare SA

A Phase 3, Multicenter, Randomized, Double-blind, Active Control Study to Evaluate the Safety and Efficacy of IV Pro-netupitant/Palonosetron (260 mg/0.25 mg) Combination for the Prevention of Chemotherapy-induced Nausea and Vomiting in Repeated Chemotherapy Cycles in Patients Receiving Highly Emetogenic Chemotherapy

NEPA-15-18 is a clinical study assessing safety of pro-netupitant and palonosetron, two antiemetic drugs, given with oral dexamethasone. The objective of the study is to evaluate if pro-netupitant and palonosetron are safe when administered to prevent nausea and vomiting after administration of repeated cycles of chemotherapy.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
405

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Graz, Austria, 8036
        • University Hospital Graz, Department of Internal Medicine
      • Krems, Austria
        • Krems Country Hospital
      • Linz, Austria, 4020
        • Hospital Elisabethinen Linz GmbH, Internal Department #1 - Hemato-Oncology
      • Linz, Austria, 4021
        • General Hospital Linz GmbH, Internal Medicine Department #3 - Center for Hematology and Medical Oncology
      • St. Poelten, Austria
        • University Hospital St. Poelten,1st Medical Department
  • Croatia
      • Osijek, Croatia
        • Clinical Hospital Centre Osijek
      • Varazdin, Croatia
        • General Hospital Varazdin
      • Zagreb, Croatia
        • Clinical Hospital Center "Sestre Milosrdnice"
      • Zagreb, Croatia
        • University Hospital Centre Zagreb "Jordanovac"
  • Czechia
      • Brno, Czechia
        • University Hospital
      • Brno, Czechia
        • University Hospital Brno. Clinic of Pulmonary Diseases and Tuberculosis
      • Novy Jicin, Czechia
        • Hospital Novy Jicin, Department of Oncology
      • Prague, Czechia
        • Hospital Na Bulovce
      • Prague, Czechia, 140 59
        • Thomayer's Hospital, Clinic of Pneumology
      • Usti nad Labem, Czechia
        • Masaryk's Hospital Usti nad Labem, Oncology Dept
  • Germany
      • Bielefeld, Germany
        • Onkoligische Schwerpunktpraxis Bielefeld
      • Hamburg, Germany
        • OncoResearch Lerchenfeld GmbH
      • Hannover, Germany
        • Hannover Medical School
      • Leipzig, Germany
        • Universitaetsklinikum Leipzig; Universitaeres Krebszentrum (UCCL)
      • München, Germany
        • Staedtisches Klinikum Muenchen GmbH; Klinikum N euperlach
  • Israel
      • Ashkelon, Israel
        • Barziali Medical Center, Oncology Unit
      • Beer Sheva, Israel
        • Soroka University Medical Center,Oncology division
      • Haifa, Israel
        • Rambam Health Care Campus
  • Italy
      • Avellino, Italy
        • S. G. Moscati Hospital, Medical Oncology Division
      • Meldola, Italy
        • cientific Institute of Romagna for the Study and Treatment of Cancer (IRST), IRCCS
      • Milan, Italy
        • National Cancer Institute, IRCCS, Medical Oncology Department
      • Monza, Italy
        • Azienda Socio Sanitaria Territoriale-Monza (ASST-Monza) - Oncology Department
      • Potenza, Italy
        • Regional Hospital "San Carlo"
      • Vimercate, Italy
        • Local Healthcare Company of Vimercate (ASST Vimercate)
  • Poland
      • Gdynia, Poland
        • Provincial Hospitals in Gdynia Sp. z o.o. (LLC)
      • Poznan, Poland, 60-569
        • Lord's Transfiguration Teaching Hospital, Department of Chemotherapy
      • Prabuty, Poland, 82-550
        • Specialist Hospital in Prabuty Sp. z o .o. (LLC), Department of Pulmonology
      • Tarnobrzeg, Poland
        • Zofia Zamoyska nee Tarnowska Provincial Hospital in Tarnobrzeg
      • Torun, Poland
        • Ludwik Rydygier Provincial Hospital
      • Warsaw, Poland, 02-781
        • Maria Sklodowska-Curie Institute of Oncology, Department of Lung and Thoracic Cancers
      • Warsaw, Poland, 03-291
        • MAGODENT Sp. z o .o. (LLC), Branch No. 4, Department of Clinical Oncology/Chemotherapy
  • Serbia
      • Belgrade, Serbia
        • Military Medical Academy
      • Belgrade, Serbia
        • Clinical Center of Serbia, Clinic of Pulmonology
      • Belgrade, Serbia
        • Clinical Hospital Center Bezanijska Kosa, Clinic of Oncology
      • Belgrade, Serbia
        • Institute of Oncology and Radiology of Serbia, Clinic of Medical Oncology
      • Sremska Kamenica, Serbia
        • Oncology Institute of Vojvodina
      • Sremska Kamenica, Serbia
        • Institute of Pulmonary Diseases of Vojvodina, Pulmonary Oncology Clinic
  • South Africa
      • George, South Africa
        • GVI Outeniqua Oncology Unit
      • Johannesburg, South Africa
        • Medical Oncology Centre of Rosebank
  • Spain
      • Avila, Spain, 05004
        • Our Lady of Sonsoles Hospital
      • Madrid, Spain, 28035
        • Hospital Puerta de Hierro
      • Madrid, Spain
        • Hospital La Paz, Oncology Department
      • Madrid, Spain
        • University Hospital Quiron Madrid, Department of Oncology
    • Andalucia
      • Sevilla, Andalucia, Spain
        • Hospital Nuestra Señora de Valme
  • Ukraine
      • Chernivtsi, Ukraine, 58013
        • Chernivtsi Regional Clinical Oncology Center, Day Care Unit
      • Dnipropetrovsk, Ukraine, 49055
        • Clinical Oncology Center, Department of Chemotherapy
      • Dnipropetrovsk, Ukraine, 49102
        • Dnipropetrovsk City Multispecialty Clinical Hospital #4, Department of Chemotherapy
      • Ivano-Frankivsk, Ukraine, 76000
        • Regional Clinical Oncology Center, Chemotherapy Department
      • Kharkiv, Ukraine, 61024
        • S.P. Hryhoriev Institute of Medical Radiology, Department of Chemotherapy
      • Kharkiv, Ukraine, 61070
        • Kharkiv Regional Clinical Oncology Center, Chemotherapy Department #1
      • Khmelnytskyi, Ukraine, 29009
        • Khmelnytskyi Regional Oncology Center, Surgery Department #1
      • Kryvyi Rih, Ukraine, 50048
        • Kryvyi Rih Oncology Center, Department of Chemotherapy
      • Lviv, Ukraine, 79031
        • Lviv State Regional Treatment and Diagnostics Oncology Center, Department of Chemotherapy
      • Ternopil, Ukraine, 46023
        • Ternopil Regional Public Clinical Oncology Center
      • Uzhhorod, Ukraine, 88014
        • Zakarpattia Regional Clinical Oncology Center, Department of Chemotherapy
      • Uzhhorod, Ukraine, 88000
        • LTD Unimed Adjara
      • Vinnytsia, Ukraine, 21029
        • Vinnytsia Regional Clinical Oncology Center, Department of Chemotherapy
      • Zaporizhia, Ukraine, 69040
        • Zaporizhia Regional Clinical Oncology Center, Thoracic Department
  • United States
    • California
      • Santa Monica, California, United States, 90403-480
        • Sarcoma Oncology Center
      • Whittier, California, United States, 90603
        • The Oncology Institute of Hope and Innovation
    • Colorado
      • Grand Junction, Colorado, United States, 81501
        • St. Mary's Medical Center
    • Florida
      • Miami, Florida, United States, 33143
        • Well Pharma Medical Research Corporation
    • Illinois
      • Peoria, Illinois, United States, 61615-7822
        • Illinois CancerCare
    • Indiana
      • Bloomington, Indiana, United States, 47403
        • Indiana University Health Bloomington
    • Louisiana
      • Alexandria, Louisiana, United States, 71301
        • CHRISTUS St. Frances Cabrini Hospital
    • New York
      • East Setauket, New York, United States, 11733
        • North Shore Hematology Oncology Associates PC
    • Ohio
      • Canton, Ohio, United States, 44718
        • Gabrail Cancer Center Research
    • Tennessee
      • Germantown, Tennessee, United States, 38138
        • West Cancer Center
      • Knoxville, Tennessee, United States, 37909
        • Provision Center For Biomedical Research

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Cycle 1

  • 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 at least 4 repeated consecutive cycles of the following highly emetogenic reference chemotherapies (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) >250mg/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.

Cycles 2 to 4:

The following inclusion criteria must be checked prior to inclusion at each repeated cycle:

  • Participation in the study during the next cycle of chemotherapy is considered appropriate by the Investigator and does not pose unwarranted risk to the patient.
  • Scheduled to receive the same chemotherapy regimen as Cycle 1 or one of the reference chemotherapies as defined in Inclusion criterion 5 for Cycle 1.
  • 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.
  • Adequate hematologic and metabolic status according to the Investigator's opinion.

Exclusion Criteria:

Cycle 1

  • Lactating woman.
  • Active infection or uncontrolled disease except for malignancy that may pose unwarranted risks in administering the study drugs to the patient.
  • Current use of illicit drugs or current evidence of alcohol abuse.
  • Scheduled to receive moderately or highly emetogenic chemotherapies 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 chemotherapy 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 chemotherapy administration on Day 1.
  • Symptomatic primary or metastatic CNS malignancy.
  • Known hypersensitivity or contraindication to 5-HT3 receptor antagonists, to dexamethasone or to NK-1 receptor antagonists.
  • Known contraindication to the IV administration of 50 mL 5% glucose solution.
  • Previously received an NK-1 receptor antagonist.
  • Participation in a previous clinical trial involving IV pro-netupitant or oral netupitant administered alone or in combination with 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 reference chemotherapy administration on Day 1. Topical and inhaled corticosteroids are permitted.
  • Scheduled to receive bone marrow transplantation and/or stem cell rescue therapy.
  • Scheduled to receive any strong or moderate inhibitor of CYP3A4 or its intake within 1 week prior to Day 1.
  • Scheduled to receive any of the following CYP3A4 substrates within 1 week prior to Day 1: terfenadine, cisapride, astemizole, pimozide.
  • Received within 4 weeks prior to Day 1 or scheduled to receive any CYP3A4 inducer.
  • Any medication with known or potential antiemetic activity within 24 hours prior to the start of reference chemotherapy administration on Day 1 of Cycle 1, including but not limited to 5-HT3 receptor antagonists and NK-1 receptor antagonists
  • History or predisposition to cardiac conduction abnormalities, except for incomplete right bundle branch block
  • History of Torsade de Point or known history of risk factors for Torsade de Point (heart failure, hypokalemia, family history of Long QT Syndrome).
  • Severe cardiovascular diseases diagnosed within 3 months prior to Day 1 of first cycle, including myocardial infarction, unstable angina pectoris, significant valvular or pericardial disease, history of ventricular tachycardia, symptomatic Congestive Heart Failure (CHF) New York Heart Association (NYHA) class III-IV, and severe uncontrolled arterial hypertension.
  • Any illness or condition that, in the opinion of the Investigator, may confound the results of the study or pose unwarranted risks in administering the investigational product to the patient.
  • Concurrent medical condition that would preclude administration of dexamethasone such as systemic fungal infection or uncontrolled diabetes.

Cycles 2 to 4:

The following exclusion criteria must be checked prior to inclusion in each repeated cycle:

  • Lactating woman.
  • Active infection or uncontrolled disease except for malignancy that may pose unwarranted risks in administering the study drugs to the patient.
  • Started any of the restricted medications.
  • Any vomiting, retching, or nausea (grade ≥ 1 as defined by National Cancer Institute) within 24 hours prior to the start of reference chemotherapy administration on Day 1.
  • Received or is scheduled to receive radiation therapy to the abdomen or the pelvis within 1 week prior to the start of the reference chemotherapy administration on Day 1 or between Days 1 to 5.
  • Symptomatic primary or metastatic CNS malignancy.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Pro-netupitant/Palonosetron plus Dexamethasone
Intravenous Pro-netupitant/Palonosetron (260 mg/0.25 mg) powder for solution for infusion (on Day 1) with oral dexamethasone prior to each scheduled chemotherapy cycle
Drug: Dexamethasone
Drug: Pro-netupitant/Palonosetron
Other Names:
  • IV NEPA FDC
Active Comparator: Netupitant/Palonosetron plus Dexamethasone
Oral netupitant/palonosetron (300 mg/0.50 mg) hard capsule (on Day 1) with oral dexamethasone prior to each scheduled chemotherapy cycle
Drug: Dexamethasone
Drug: Netupitant/Palonosetron
Other Names:
  • Oral NEPA FDC

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Percentage of Patients With Adverse Events
Time Frame: Participants will be followed for the duration of the chemotherapy, an expected average duration of up to 14 weeks assuming a maximum of 4 chemotherapy cycles given every 3 weeks.
This is a safety study where Adverse Events is the primary outcome (defined by the current ICH Guideline for Good Clinical Practice). Patients are randomized according to a 1:1 ratio (IV NEPA FDC : oral NEPA FDC). No formal comparison is planned, the presence of a control in the same patient population helps interpret any unexpected safety finding in the experimental arm. It is expected that the number of patients randomized to the test group, i.e., 200, will allow approximately 100 patients to be treated with the test drug for 4 cycles. Based on 100 patients treated at Cycle 4 with the IV NEPA FDC , if a given Adverse Event (AE) is not observed, an AE incidence of 3% or greater can be excluded with 95% confidence.
Participants will be followed for the duration of the chemotherapy, an expected average duration of up to 14 weeks assuming a maximum of 4 chemotherapy cycles given every 3 weeks.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Percentage of Patients With Complete Response (CR) Defined as no Emesis, no Rescue Medication, in the Acute Phase
Time Frame: 0-24 hours
0-24 hours
Percentage of Patients With Complete Response (CR) Defined as no Emesis, no Rescue Medication, in the Delayed Phase
Time Frame: >24-120 hours
>24-120 hours
Percentage of Patients With Complete Response (CR) Defined as no Emesis, no Rescue Medication, in the Overall Phase
Time Frame: 0-120 hours
0-120 hours
Percentage of Patients With no Emetic Episodes in the Acute Phase
Time Frame: 0-24 hours
0-24 hours
Percentage of Patients With no Emetic Episodes in the Delayed Phase
Time Frame: >24-120 hours
>24-120 hours
Percentage of Patients With no Emetic Episodes in the Overall Phase
Time Frame: 0-120 hours
0-120 hours
Percentage of Patients With no Significant Nausea (VAS <25 mm) During the Acute Phase
Time Frame: 0-24 hours
0-24 hours
Percentage of Patients With no Significant Nausea (VAS <25 mm) During the Delayed Phase
Time Frame: >24-120 hours
>24-120 hours
Percentage of Patients With no Significant Nausea (VAS <25 mm) During the Overall Phase
Time Frame: 0-120 hours
0-120 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Helsinn Healthcare SA

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
PSI CRO

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 3, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 5, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 6, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 20, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 18, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • NEPA-15-18

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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