An Efficacy and Safety Study of Oral Netupitant and Palonosetron for the Prevention of Nausea and Vomiting

NCT ID: NCT01339260

Last Updated: 2014-11-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1455 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-04-30

Brief Summary

NETU-08-18 is a two-arm clinical study assessing efficacy and safety of a single oral dose of netupitant and palonosetron, two antiemetic drugs, versus oral palonosetron, both given with oral dexamethasone. The objective of the study is to demonstrate that netupitant and palonosetron are more effective than palonosetron alone, to prevent nausea and vomiting induced by moderately emetogenic cancer chemotherapy after administration of repeated cycles of chemotherapy.

Detailed Description

NETU-08-18 is a two-arm clinical study assessing efficacy and safety of a single oral dose of netupitant and palonosetron, two antiemetic drugs, versus oral palonosetron, both given with oral dexamethasone. Study is organised in two phases: cycle-1 and a multi-cycle extension. Safety assessment is performed separately in cycle 1 (arm 1 and arm 2) and in multi-cycle extension (arm 3 and arm 4).

Conditions

Chemotherapy-Induced Nausea and Vomiting

Study Design

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

Study Groups

Netupitant and Palonosetron+dexamethasone-cycle 1

Oral netupitant/palonosetron (300 mg/0.50 mg) hard capsule with oral dexamethasone (12 mg), both given on Day 1, prior to each scheduled chemotherapy cycle

Group Type: EXPERIMENTAL

Netupitant and Palonosetron

Intervention Type: DRUG

Dexamethasone

Intervention Type: DRUG

Palonosetron+dexamethasone-cycle 1

Oral palonosetron 0.50 mg (Aloxi) with oral dexamethasone (20 mg) both given on Day 1, prior to each scheduled chemotherapy cycle

Group Type: ACTIVE_COMPARATOR

Palonosetron

Intervention Type: DRUG

Dexamethasone

Intervention Type: DRUG

Netupitant and Palonosetron+dexamethasone-multicycle extension

Oral netupitant/palonosetron (300 mg/0.50 mg) hard capsule with oral dexamethasone (12 mg), both given on Day 1, prior to each scheduled chemotherapy cycle

Group Type: EXPERIMENTAL

Netupitant and Palonosetron

Intervention Type: DRUG

Dexamethasone

Intervention Type: DRUG

Palonosetron+dexamethasone-multicycle extension

Oral palonosetron 0.50 mg (Aloxi) with oral dexamethasone (20 mg) both given on Day 1, prior to each scheduled chemotherapy cycle

Group Type: ACTIVE_COMPARATOR

Palonosetron

Intervention Type: DRUG

Dexamethasone

Intervention Type: DRUG

Interventions

Netupitant and Palonosetron

Intervention Type: DRUG

Palonosetron

Intervention Type: DRUG

Dexamethasone

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Naïve to cytotoxic chemotherapy. Previous biological or hormonal therapy will be permitted.
• Scheduled to receive first course of an anthracycline and cyclophosphamide containing moderately emetogenic chemotherapy (MEC) regimen for the treatment of a solid malignant tumor: cyclophosphamide I.V. (500 to 1500 mg/m2) and I.V. doxorubicin (more or equal to 40 mg/m2) or cyclophosphamide I.V. (500 to 1500 mg/m2) and I.V. epirubicin (more or equal to 60 mg/m2).
• If scheduled to receive chemotherapy agents of minimal to low emetogenic potential they could be given on any day.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2.
• Female patients of either non-childbearing potential or child-bearing potential with a commitment to use contraceptive methods throughout the clinical trial
• Hematologic and metabolic status adequate for receiving a moderately emetogenic regimen based on laboratory criteria (Total Neutrophils,Platelets, Bilirubin, Liver enzymes, Serum Creatinine or Creatinine Clearance)

• Participation in the study during the next cycle of chemotherapy is considered appropriate by the investigator Satisfactory study compliance in the preceding cycle of chemotherapy and related study procedures.
• Scheduled to receive the same chemotherapy regimen as cycle 1
• Adequate hematologic and metabolic status as defined for cycle 1

Exclusion Criteria

• If female, pregnant or lactating.
• Current use of illicit drugs or current evidence of alcohol abuse.
• Scheduled to receive any highly emetogenic chemotherapy (HEC) from Day 1 to Day 5 or moderately emetogenic chemotherapy (MEC) from Day 2 to Day 5 following the allowed MEC regimen.
• Received or is scheduled to receive radiation therapy to the abdomen or the pelvis within 1 week prior to Day 1 or between Days 1 to 5 in cycle 1.
• Any vomiting, retching, or mild nausea within 24 hours prior to Day 1.
• Symptomatic primary or metastatic central nervous system (CNS) malignancy.
• Active peptic ulcer disease, gastrointestinal obstruction, increased intracranial pressure, hypercalcemia, an active infection or any uncontrolled medical condition (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, CINV) or pose unwarranted risks in administering the study drugs to the patient.
• Known hypersensitivity or contraindication to 5-HT3 receptor antagonists or dexamethasone.
• Previously received a neurokin-1 (NK1) receptor antagonist
• Participation in a clinical trial involving oral netupitant administered in combination with palonosetron.
• Any investigational drugs taken within 4 weeks prior to Day 1 of cycle 1, and/or is scheduled to receive any investigational drug during the study.
• Systemic corticosteroid therapy at any dose within 72 hours prior to Day 1 of cycle 1.
• 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 Day 1 of cycle 1
• Scheduled to receive any strong or moderate inhibitor of cytocrome P450 3A4 (CYP3A4) or its intake within 1 week prior to Day 1.
• Scheduled to receive any of the following CYP3A4 substrates: terfenadine, cisapride, astemizole, pimozide.
• Scheduled to receive any CYP3A4 inducer or its intake within 4 weeks prior to Day 1.
• History or predisposition to cardiac conduction abnormalities, except for incomplete right bundle branch block.
• History of risk factors for Torsade de Point (heart failure, hypokalemia, family history of Long QT Syndrome).
• Severe cardiovascular diseases, including myocardial infarction within 3 months prior to Day 1, 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.

• If female, pregnant or lactating
• Active infection or uncontrolled disease except for malignancy.
• Started any of the restricted medications.
• Any vomiting, retching, or mild nausea within 24 hours prior to Day 1.

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

Sponsors

Parexel

INDUSTRY

Sponsor Role: collaborator

Helsinn Healthcare SA

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Anniston Oncology/Regional Medical Center

Anniston, Alabama, United States

Northwest Alabama Cancer Center

Muscle Shoals, Alabama, United States

Genesis Cancer Centre

Hot Springs, Arkansas, United States

Compassionate Cancer Care Medical Group Inc

Corona, California, United States

Compassionate Cancer Centre Medical Group

Fountain Valley, California, United States

American Institute of Research

Los Angeles, California, United States

Facey Medical Group

Mission Hills, California, United States

Compassionate Cancer Care Medical Group

Riverside, California, United States

American Institute of Research

Whittier, California, United States

Denver Health and Hospital Authority

Denver, Colorado, United States

Palm Beach Institute of Hematology and Oncology

Boynton Beach, Florida, United States

Baptist Cancer Institute

Jacksonville, Florida, United States

Deaconess Clinic Downtown

Evansville, Indiana, United States

Floyd Memorial Cancer Center of Indiana

New Albany, Indiana, United States

Kentucky Cancer Clinic

Hazard, Kentucky, United States

The John R Marsh Cancer Center

Hagerstown, Maryland, United States

Fallon Clinic at Worcester Medical Center

Worcester, Massachusetts, United States

Duke University Medical Center

Durham, North Carolina, United States

Piedmont Hematology Oncology Associates PA

Winston-Salem, North Carolina, United States

Tri-County Hematology and Oncolgy Associates Inc.

Massillon, Ohio, United States

Signal Point Clinical Research Center LLC

Middletown, Ohio, United States

Charleston Cancer Center

Charleston, South Carolina, United States

Charleston Hematology Oncology

Charleston, South Carolina, United States

Wellmont Medical Associates-Oncology and Hematology

Bristol, Tennessee, United States

Cancer Specialists of South Texas, P.A.

Corpus Christi, Texas, United States

The University of Texas Health Center

Tyler, Texas, United States

Northern Utah Associates Hematology / Oncology

Ogden, Utah, United States

Northwest Medical Specialties

Tacoma, Washington, United States

Hospital Italiano de Cordoba

Córdoba, , Argentina

Clínica Universitaria Reina Fabiola (Universidad Católica de Córdoba)

Córdoba, , Argentina

Instituto Oncológico de Córdoba - Sanatorio Aconcagua

Córdoba, , Argentina

Centro Oncológico Integral (COI)

Mar del Plata, , Argentina

Centro Oncologico de Integracion Regional (COIR)

Mendoza, , Argentina

Instituto Médico CER [Oncology]

Quilmes, , Argentina

Sanatorio Parque

Rosario, , Argentina

Centro Medico San Roque

San Miguel de Tucumán, , Argentina

ISIS Clinica Especializada

Santa Fe, , Argentina

Bobruisk Interregional Oncological Dispensary

Babruysk, , Belarus

Brest Regional Oncological Dispensary

Brest, , Belarus

Gomel Regional Clinical Oncological Dispensary

Brest, , Belarus

Minsk city Clinical Oncological Dispensary [Oncology]

Minsk, , Belarus

State institution N.N. Alexandrov Republican Scientific and Practical Center of Oncology and Medical Radiology

Minsk, , Belarus

Mogilev Regional Oncological Dispensary [Oncology]

Mogilev, , Belarus

OXION-Medicina Oncológica

Belo Horizonte, , Brazil

Centro de Pesquisas Clínicas em Oncologia

Cachoeiro de Itapemirim, , Brazil

IPCEM - Centro de Ciências da Saúde - Universidade de Caxias

Caxias do Sul, , Brazil

Hospital Araújo Jorge

Goiânia, , Brazil

Clinica de Neoplasias do Litoral

ItajaÃ, , Brazil

Clinica De Oncologia De Porto Alegre S S Ltda

Porto Alegre, , Brazil

Hospital Moinhos de Vento

Porto Alegre, , Brazil

Instituto Ribeirãopretano de Combate ao Cancer

Ribeirão Preto, , Brazil

Oncotrat Oncologia Medica Ltda [Oncology]

Rio de Janeiro, , Brazil

Nucleo de Oncologia da Bahia

Salvador Bahia, , Brazil

Hospital Santa Cruz

São Paulo, , Brazil

Casa de Saude Santa Marcelina

São Paulo, , Brazil

SHATO "Sveti Mina"

Blagoevgrad, , Bulgaria

MHAT Dr. Tota Venkova [Oncology]

Gabrovo, , Bulgaria

Specialized Hospital for Active Treatment of Oncology

Haskovo, , Bulgaria

UMHAT ""Dr. Georgi Stranski"" Dept. Medical Oncology

Pleven, , Bulgaria

UMHAT "Sveti Georgi" [Clinic of Oncology and Hematology]

Plovdiv, , Bulgaria

District Dispensery with Stationary - Sofia District

Sofia, , Bulgaria

UMHAT "Tsaritsa Yoanna - ISUL" Ltd.Medical Oncology Clinic

Sofia, , Bulgaria

Specialized Hospital for Active Treatment in Oncology

Sofia, , Bulgaria

Specialized Hospital for Active Treatment of Onclogy Diseases - Sofia City

Sofia, , Bulgaria

Complex Oncology Centre

Stara Zagora, , Bulgaria

COC - Veliko Tarnovo Dept. Medical Oncology

Veliko Tarnovo, , Bulgaria

Comprehensive Cancer Center - Vratsa Dept. of Palliative Care

Vratsa, , Bulgaria

Županijska bolnica Cakovec

Čakovec, , Croatia

Klinicki bolnicki centar Osijek [Oncology]

Osijek, , Croatia

Opca bolnica Pula [Odjel za onklologiju]

Pula, , Croatia

KBC Rijeka [Gastroenterology]

Rijeka, , Croatia

Opca bolnica Varazdin [Odjel za hem.onko i klin.imun.]

Varaždin, , Croatia

Opca Bolnica Zadal Ulica

Zadar, , Croatia

Klinički bolnički centar Zagreb [Oncology]

Zagreb, , Croatia

Klinicka bolnica [Sestre milosrdnice]

Zagreb, , Croatia

Klinika za tumore [Odjel za kemoter. i internisticku onkolog

Zagreb, , Croatia

Klinik und Poliklinik für Onkologie und Hämatologie Universitatsmedizin Charite Mitte

Berlin, , Germany

Gynäkologische Arztpraxis

Berlin, , Germany

OncoResearch Lerchenfeld UG

Hamburg, , Germany

Schwerpktprxs gynäkolog Onkologie Prof. Dr. Diel, Dr. Gebert

Mannheim, , Germany

Rotkreuzklinikum [München]

München, , Germany

Tumorzentrum Munchen Sued - Städtisches Klinikum [Hämato-, Onkologie + Palliativmed]

München, , Germany

Staedtisches Krankenhaus Muenchen Neuperlach

München, , Germany

OncoPRO GbR Dr. R. Dengler, Dr. A. Kröber Gesellschaft für klinische Studien in der ambulanten Hämatologie und Onkologie

Regensburg, , Germany

Universitätsklinikum Tübingen

Tübingen, , Germany

Praxis Dr. G. Dresemann

Velen, , Germany

Onkologische Gemeinschaftspraxis Dr. med M. Perker / PF Dr. med M. Sandherr

Weilheim, , Germany

Semmelweis Egyetem Kútvölgyi Klinikai Tömb

Budapest, , Hungary

Fővárosi Önkormányzat Uzsoki utcai Kórház

Budapest, , Hungary

Petz Aladár Megyei Oktató Kórház [Onkoradiológiai Oszt

Győr, , Hungary

Bács-Kiskun Megyei Önkormányzat Kórháza, Szegedi

Kecskemét, , Hungary

Borsod-Abaúj-Zemplén Megyei Kórház és Egyetemi Oktató Kórház

Miskolc, , Hungary

Josa Andras Oktato Korhaz [Onkologiai Osztaly]

Nyíregyháza, , Hungary

Pécsi Tudományegyetem Klinikai Köpont

Pécs, , Hungary

Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz

Szolnok, , Hungary

HCG - Multy Speciality Hospital

Ahmedabad, , India

Hemato-Oncology Clinic Ahmedabad Pvt Ltd

Ahmedabad, , India

Sujan Surgical Cancer Hospital and Amracvati Cancer Foundation

Amravati, , India

Sri Venkateshwara Hospital [Medical Oncology]

Bangalore, , India

Apollo Speciality Hospital

Chennai, , India

Dr. Kamahshi Memorial Hospital [Oncology]

Chennai, , India

BIBI General Hospital & Cancer Centre [Oncology]

Hyderabad, , India

Yashoda B-Block Hospital

Hyderabad, , India

B.P.Poddar Hospital and Medical Research Ltd

Kolkata, , India

Apollo Gleneagles Hospitals Kolkata

Kolkata, , India

Shatabdhi Superspeciality Hospital

Nashik, , India

Grant Medical Foundation - Ruby Hall Clinic

Pune, , India

City Cancer Centre [Surgical and Medical Oncology]

Vijayawada, , India

Fondazione Poliambulanza Istituto Ospedaliero

Brescia, , Italy

Ospedale Vito Fazzi, ASL Lecce

Lecce, , Italy

Presidio Ospedaliero "Alessandro Manzoni", AO Provincia di Lecco

Lecco, , Italy

Ospedale Sacro Cuore e Don Calabria - Negrar

Negrar, , Italy

Ospedale S.Carlo di Potenza [U.O. di Oncologia Medica]

Potenza, , Italy

Centro Oncologico De Chihuahua

Chihuahua City, , Mexico

Hospital de Jesus

México, , Mexico

Centro Medico Quirurgico

México, , Mexico

OCA Hospital/Monterrey International Research Center

Monterrey, , Mexico

Centro Regiomontano de Investigación Clínica

Monterrey, , Mexico

Bialostockie Centrum Onkologii im. M.Sklodowskiej-Curie

Bialystok, , Poland

Wojewodzki Szpital Zespolony w Elblagu, Oddzial Onkologiczny

Elblag, , Poland

Niepubliczny Specjalist. Onkol. Zaklad Opieki Zdrowotnej

Kościerzyna, , Poland

Wojewodzki Szpital Specjalistyczny im. M.Kopernika

Lodz, , Poland

Olsztynski Osrodek Onkologiczny "KOPERNIK"

Olsztyn, , Poland

Szpital Rejonowy im. dr J. Rostka w Raciborzu

Racibórz, , Poland

Wojewodzki Szpital Specjalistyczny im. J. Korczaka

Słupsk, , Poland

Centrum Onkologii - Instytut im. Marii Sklodowskiej - Curie

Warsaw, , Poland

NZOZ Magodent - Centrum Medczyne Ostrobramska

Warsaw, , Poland

Szpital Wojewodzki w Lomzy im. Kardynala S. Wyszynskiego

Łomża, , Poland

Spitalul Judetean de Urgenta "Dr. Constantin Opris" Baia-Mare [Oncologie Medicala]

Baia Mare, , Romania

Spitalul Universitar de Urgenta Elias [Oncologie Medicala]

Bucharest, , Romania

Spitalul Clinic CF nr.2 Bucuresti [Oncologie Medicala]

Bucharest, , Romania

Spitalul Universitar de Urgenta Bucuresti

Bucharest, , Romania

Institutul Oncologic "Prof. Dr. Alex. Trestioreanu" [Sectia Clinica Radioterapie II]

Bucharest, , Romania

Oncolab - Oncology Center Craiova

Craiova, , Romania

Institutul Regional de Oncologia

Iași, , Romania

Spitalul Municipal Onesti [Sectia Oncologie Medicala]

Onești, , Romania

Spitalul Clinic Judetean Mures

Tg Mures, , Romania

Oncomed SRL

Timișoara, , Romania

GUZ Arkhangelsk Regional Clinical Oncological Dispensary

Arkhangelsk, , Russia

Ivanovo Regional Oncological Dispensary [Chemotherapy]

Ivanovo, , Russia

GAUZ Republic Clinical Oncology Dispensary of Ministry of Health of Republic Tatarstan

Kazan', , Russia

GOU VPO Krasnoyarsk State Medical University n.a. prof. V.F.

Krasnoyarsk, , Russia

GUZ Lipetsk Regional Oncology Dispensary [General Oncology]

Lipetsk, , Russia

GUZ Regional Oncology Dispensary #2

Magnitogorsk, , Russia

Russian Cancer Research Center

Moscow, , Russia

SBHI of Moscow City Oncology Clinical Hospital #62

Moscow, , Russia

MBUZ City Clinical Hospital #1

Novosibirsk, , Russia

FGBU Medical Radiology Scientific Center

Obninsk, , Russia

GUZ Perm Regional Oncology Dispensary

Perm, , Russia

GUZ Pyatigorsk Oncology Dispensary [Outpatient Department]

Pyatigorsk, , Russia

GOU VPO - Ryazan State Med. Univer. n.a. I.I.Pavlov based Ryazan Regio

Ryazan, , Russia

GUZ "Leningrad Regional Oncology Dispensary"

Saint Petersburg, , Russia

City Oncology Dispensary

Saint Petersburg, , Russia

GOU VPO Saint-Petersburg State Medical University n.a. acad.

Saint Petersburg, , Russia

St. Petersburg Clinical Oncology Dispesary - 3rd Gynecology D

Saint Petersburg, , Russia

FGU Research Institute of Oncology n.a. N.N.Petrov of Rosmed

Saint Petersburg, , Russia

GUZ Samara Regional Clinical Oncology Dispensary

Samara, , Russia

Stavropol Regional Clinical Oncology Dispensary

Stavropol, , Russia

GBUZ - Clinical Oncology Dispensary of MoH of Republic Bahkortostan

Ufa, , Russia

GUZ Republican Clinical Oncological Dispensary of public

Ufa, , Russia

Komunalnyi "Cherkaskyi oblasnyi onkolohichnyi dyspanser" Cherkaskoi oblasnoi rady, oblasnyi onkokhimioterapevtychnyi tsentr, m. Cherkasy

Cherkasy, , Ukraine

Komunalnyi likuvalno-profilaktychnyi zaklad "Chernigivskyi

Chernihiv, , Ukraine

Chmelnytskyi Regional Clinical Oncology Centre [Oncology]

Chmelnytskyi, , Ukraine

Komunalnyizaklad Miska bahatoprofilna klinichna likarnia #4

Dnipropetrovks, , Ukraine

Donetskyi oblasnyi protypukhlynnyi tsentr

Donetsk, , Ukraine

Kharkivskyi oblasnyi onkologichnyi klinichnyi tsentr

Kharkiv, , Ukraine

Kyirskyi Miskyi klinichnyi onkolohichnyi tsentr

Kyiv, , Ukraine

KZ KOR Kyivskyi oblasnyi onkologichnyi dyspanser

Kyiv, , Ukraine

Lvivskyi derzhavnyi onkologichnyi regionalnyi likuvalno diahnostychyi tsentr

Lviv, , Ukraine

Odeska oblasna klinichna likarnia

Odesa, , Ukraine

Poltavskyi oblasnyi klinichnyi onkolohichnyi dyspanser Pol

Poltava, , Ukraine

Zakarpatskyi oblasnyi klinichnyi onkodyspanser

Uzhhorod, , Ukraine

Countries

United States; Argentina; Belarus; Brazil; Bulgaria; Croatia; Germany; Hungary; India; Italy; Mexico; Poland; Romania; Russia; Ukraine

References

Schwartzberg L, Karthaus M, Rossi G, Rizzi G, Borroni ME, Rugo HS, Jordan K, Hansen V. Fixed combination of oral NEPA (netupitant-palonosetron) for the prevention of acute and delayed chemotherapy-induced nausea and vomiting in patients receiving multiple cycles of chemotherapy: Efficacy data from 2 randomized, double-blind phase III studies. Cancer Med. 2019 May;8(5):2064-2073. doi: 10.1002/cam4.2091. Epub 2019 Apr 9.

Reference Type: DERIVED

PMID: 30968588 (View on PubMed)

Rugo HS, Rossi G, Rizzi G, Aapro M. Efficacy of NEPA (netupitant/palonosetron) across multiple cycles of chemotherapy in breast cancer patients: A subanalysis from two phase III trials. Breast. 2017 Jun;33:76-82. doi: 10.1016/j.breast.2017.02.017. Epub 2017 Mar 10.

Reference Type: DERIVED

PMID: 28285236 (View on PubMed)

Other Identifiers

NETU-08-18

Identifier Type: -

Identifier Source: org_study_id