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

NCT ID: NCT02517021

Last Updated: 2018-06-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 405 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-11-30
• Study Completion Date: 2016-08-31

Brief Summary

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.

Conditions

Chemotherapy-Induced Nausea and Vomiting

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

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

Group Type: EXPERIMENTAL

Pro-netupitant/Palonosetron

Intervention Type: DRUG

Dexamethasone

Intervention Type: DRUG

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

Group Type: ACTIVE_COMPARATOR

Netupitant/Palonosetron

Intervention Type: DRUG

Dexamethasone

Intervention Type: DRUG

Interventions

Pro-netupitant/Palonosetron

Intervention Type: DRUG

Netupitant/Palonosetron

Intervention Type: DRUG

Dexamethasone

Intervention Type: DRUG

Other Intervention Names

IV NEPA FDC; Oral NEPA FDC

Eligibility Criteria

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:

• 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:

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

PSI CRO

INDUSTRY

Sponsor Role: collaborator

Helsinn Healthcare SA

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Sarcoma Oncology Center

Santa Monica, California, United States

The Oncology Institute of Hope and Innovation

Whittier, California, United States

St. Mary's Medical Center

Grand Junction, Colorado, United States

Well Pharma Medical Research Corporation

Miami, Florida, United States

Illinois CancerCare

Peoria, Illinois, United States

Indiana University Health Bloomington

Bloomington, Indiana, United States

Christus St. Frances Cabrini Hospital

Alexandria, Louisiana, United States

North Shore Hematology Oncology Associates PC

East Setauket, New York, United States

Gabrail Cancer Center Research

Canton, Ohio, United States

West Cancer Center

Germantown, Tennessee, United States

Provision Center for Biomedical Research

Knoxville, Tennessee, United States

University Hospital Graz, Department of Internal Medicine

Graz, , Austria

Krems Country Hospital

Krems, , Austria

Hospital Elisabethinen Linz GmbH, Internal Department #1 - Hemato-Oncology

Linz, , Austria

General Hospital Linz GmbH, Internal Medicine Department #3 - Center for Hematology and Medical Oncology

Linz, , Austria

University Hospital St. Poelten,1st Medical Department

Sankt Pölten, , Austria

Clinical Hospital Centre Osijek

Osijek, , Croatia

General Hospital Varazdin

Varaždin, , Croatia

Clinical Hospital Center "Sestre milosrdnice"

Zagreb, , Croatia

University Hospital Centre Zagreb "Jordanovac"

Zagreb, , Croatia

University Hospital Brno. Clinic of Pulmonary Diseases and Tuberculosis

Brno, , Czechia

University Hospital

Brno, , Czechia

Hospital Novy Jicin, Department of Oncology

Nový Jičín, , Czechia

Thomayer's Hospital, Clinic of Pneumology

Prague, , Czechia

Hospital Na Bulovce

Prague, , Czechia

Masaryk's Hospital Usti nad Labem, Oncology Dept

Ústí nad Labem, , Czechia

Onkoligische Schwerpunktpraxis Bielefeld

Bielefeld, , Germany

OncoResearch Lerchenfeld GmbH

Hamburg, , Germany

Hannover Medical School

Hanover, , Germany

Universitaetsklinikum Leipzig; Universitaeres Krebszentrum (UCCL)

Leipzig, , Germany

Staedtisches Klinikum Muenchen GmbH; Klinikum N euperlach

München, , Germany

Barziali Medical Center, Oncology Unit

Ashkelon, , Israel

Soroka University Medical Center,Oncology division

Beersheba, , Israel

Rambam Health Care Campus

Haifa, , Israel

S. G. Moscati Hospital, Medical Oncology Division

Avellino, , Italy

cientific Institute of Romagna for the Study and Treatment of Cancer (IRST), IRCCS

Meldola, , Italy

National Cancer Institute, IRCCS, Medical Oncology Department

Milan, , Italy

Azienda Socio Sanitaria Territoriale-Monza (ASST-Monza) - Oncology Department

Monza, , Italy

Regional Hospital "San Carlo"

Potenza, , Italy

Local Healthcare Company of Vimercate (ASST Vimercate)

Vimercate, , Italy

Provincial Hospitals in Gdynia Sp. z o.o. (LLC)

Gdynia, , Poland

Lord's Transfiguration Teaching Hospital, Department of Chemotherapy

Poznan, , Poland

Specialist Hospital in Prabuty Sp. z o .o. (LLC), Department of Pulmonology

Prabuty, , Poland

Zofia Zamoyska nee Tarnowska Provincial Hospital in Tarnobrzeg

Tarnobrzeg, , Poland

Ludwik Rydygier Provincial Hospital

Torun, , Poland

Maria Sklodowska-Curie Institute of Oncology, Department of Lung and Thoracic Cancers

Warsaw, , Poland

MAGODENT Sp. z o .o. (LLC), Branch No. 4, Department of Clinical Oncology/Chemotherapy

Warsaw, , Poland

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

Belgrade, , Serbia

Military Medical Academy

Belgrade, , Serbia

Institute of Pulmonary Diseases of Vojvodina, Pulmonary Oncology Clinic

Kamenitz, , Serbia

Oncology Institute of Vojvodina

Kamenitz, , Serbia

GVI Outeniqua Oncology Unit

George, , South Africa

Medical Oncology Centre of Rosebank

Johannesburg, , South Africa

Hospital Nuestra Senora de Valme

Seville, Andalusia, Spain

Our Lady of Sonsoles Hospital

Ávila, , Spain

Hospital Puerta de Hierro

Madrid, , Spain

Hospital La Paz, Oncology Department

Madrid, , Spain

University Hospital Quiron Madrid, Department of Oncology

Madrid, , Spain

Chernivtsi Regional Clinical Oncology Center, Day Care Unit

Chernivtsi, , Ukraine

Clinical Oncology Center, Department of Chemotherapy

Dnipropetrovsk, , Ukraine

Dnipropetrovsk City Multispecialty Clinical Hospital #4, Department of Chemotherapy

Dnipropetrovsk, , Ukraine

Regional Clinical Oncology Center, Chemotherapy Department

Ivano-Frankivsk, , Ukraine

S.P. Hryhoriev Institute of Medical Radiology, Department of Chemotherapy

Kharkiv, , Ukraine

Kharkiv Regional Clinical Oncology Center, Chemotherapy Department #1

Kharkiv, , Ukraine

Khmelnytskyi Regional Oncology Center, Surgery Department #1

Khmelnytskyi, , Ukraine

Kryvyi Rih Oncology Center, Department of Chemotherapy

Kryvyi Rih, , Ukraine

Lviv State Regional Treatment and Diagnostics Oncology Center, Department of Chemotherapy

Lviv, , Ukraine

Ternopil Regional Public Clinical Oncology Center

Ternopil, , Ukraine

LTD UNIMED Adjara

Uzhhorod, , Ukraine

Zakarpattia Regional Clinical Oncology Center, Department of Chemotherapy

Uzhhorod, , Ukraine

Vinnytsia Regional Clinical Oncology Center, Department of Chemotherapy

Vinnytsia, , Ukraine

Zaporizhia Regional Clinical Oncology Center, Thoracic Department

Zaporizhia, , Ukraine

Countries

United States; Austria; Croatia; Czechia; Germany; Israel; Italy; Poland; Serbia; South Africa; Spain; Ukraine

References

Schwartzberg L, Roeland E, Andric Z, Kowalski D, Radic J, Voisin D, Rizzi G, Navari R, Gralla RJ, Karthaus M. Phase III safety study of intravenous NEPA: a novel fixed antiemetic combination of fosnetupitant and palonosetron in patients receiving highly emetogenic chemotherapy. Ann Oncol. 2018 Jul 1;29(7):1535-1540. doi: 10.1093/annonc/mdy169.

Reference Type: DERIVED

PMID: 29722791 (View on PubMed)

Other Identifiers

NEPA-15-18

Identifier Type: -

Identifier Source: org_study_id