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

Chemotherapy-Induced Nausea and Vomiting Clinical Trial

Official title:

A Phase III Multicenter, Randomized, Double-blind, Double-dummy, Active-controlled, Parallel Group Study of the Efficacy and Safety of Oral Netupitant Administered in Combination With Palonosetron and Dexamethasone Compared to Oral Palonosetron and Dexamethasone for the Prevention of Nausea and Vomiting in Cancer Patients Receiving Moderately Emetogenic Chemotherapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01339260
• Other study ID #: NETU-08-18
• Status: Completed
• Phase: Phase 3
• First received: April 19, 2011
• Last updated: November 19, 2014
• Start date: April 2011

Study information

• Verified date: November 2014
• Source: Helsinn Healthcare SA
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationArgentina: Ministry of HealthBelarus: Ministry of HealthBrazil: Ministry of HealthBrazil: National Committee of Ethics in ResearchHungary: National Institute of PharmacyGermany: Federal Institute for Drugs and Medical DevicesRomania: National Medicines AgencyRomania: Ethics CommitteeBulgaria: Bulgarian Drug AgencyBulgaria: Ethics committeeCroatia: Agency for Medicinal Product and Medical DevicesCroatia: Ethics CommitteePoland: National Institute of MedicinesPoland: Ethics CommitteeItaly: National Monitoring Centre for Clinical Trials - Ministry of HealthUkraine: Ethics CommitteeUkraine: Ministry of HealthRussia: Pharmacological Committee, Ministry of HealthMexico: Ministry of HealthMexico: Ethics CommitteeIndia: Central Drugs Standard Control OrganizationIndia: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1455
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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)

The following inclusion criteria must be checked prior inclusion at each cycle of the Multiple-Cycle Extension:

• 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.

The following exclusion criteria must be checked prior inclusion at each cycle of the Multiple-Cycle Extension:

• 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.

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Chemotherapy-Induced Nausea and Vomiting
• Nausea
• Vomiting

Intervention

Drug:
• Netupitant and Palonosetron

• Palonosetron

• Dexamethasone

Locations

Country	Name	City	State
Argentina	Instituto Oncológico de Córdoba - Sanatorio Aconcagua	Cordoba
Argentina	Clínica Universitaria Reina Fabiola (Universidad Católica de Córdoba)	Córdoba
Argentina	Hospital Italiano de Cordoba	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 Tucuman
Argentina	ISIS Clinica Especializada	Santa Fe
Belarus	Bobruisk Interregional Oncological Dispensary	Bobruisk
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
Brazil	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	Casa de Saude Santa Marcelina	São Paulo
Brazil	Hospital Santa Cruz	São Paulo
Bulgaria	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	Specialized Hospital for Active Treatment in Oncology	Sofia
Bulgaria	Specialized Hospital for Active Treatment of Onclogy Diseases - Sofia City	Sofia
Bulgaria	UMHAT "Tsaritsa Yoanna - ISUL" Ltd.Medical Oncology Clinic	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
Croatia	Županijska bolnica Cakovec	Cakovec
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.]	Varazdin
Croatia	Opca Bolnica Zadal Ulica	Zadar
Croatia	Klinicka bolnica [Sestre milosrdnice]	Zagreb
Croatia	Klinicki bolnicki centar Zagreb [Oncology]	Zagreb
Croatia	Klinika za tumore [Odjel za kemoter. i internisticku onkolog	Zagreb
Germany	Gynäkologische Arztpraxis	Berlin
Germany	Klinik und Poliklinik für Onkologie und Hämatologie Universitatsmedizin Charite Mitte	Berlin
Germany	OncoResearch Lerchenfeld UG	Hamburg
Germany	Schwerpktprxs gynäkolog Onkologie Prof. Dr. Diel, Dr. Gebert	Mannheim
Germany	Rotkreuzklinikum [München]	München
Germany	Staedtisches Krankenhaus Muenchen Neuperlach	München
Germany	Tumorzentrum Munchen Sued - Städtisches Klinikum [Hämato-, Onkologie + Palliativmed]	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
Hungary	Fovárosi Önkormányzat Uzsoki utcai Kórház	Budapest
Hungary	Semmelweis Egyetem Kútvölgyi Klinikai Tömb	Budapest
Hungary	Petz Aladár Megyei Oktató Kórház [Onkoradiológiai Oszt	Gyor
Hungary	Bács-Kiskun Megyei Önkormányzat Kórháza, Szegedi	Kecskemet
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
India	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	Apollo Gleneagles Hospitals Kolkata	Kolkata
India	B.P.Poddar Hospital and Medical Research Ltd	Kolkata
India	Shatabdhi Superspeciality Hospital	Nashik
India	Grant Medical Foundation - Ruby Hall Clinic	Pune
India	City Cancer Centre [Surgical and Medical Oncology]	Vijayawada
Italy	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
Mexico	Centro Oncologico De Chihuahua	Chihuahua
Mexico	Centro Medico Quirurgico	Mexico
Mexico	Hospital de Jesus	Mexico
Mexico	Centro Regiomontano de Investigación Clínica	Monterrey
Mexico	OCA Hospital/Monterrey International Research Center	Monterrey
Poland	Bialostockie Centrum Onkologii im. M.Sklodowskiej-Curie	Bialystok
Poland	Wojewodzki Szpital Zespolony w Elblagu, Oddzial Onkologiczny	Elblag
Poland	Niepubliczny Specjalist. Onkol. Zaklad Opieki Zdrowotnej	Koscierzyna
Poland	Wojewodzki Szpital Specjalistyczny im. M.Kopernika	Lodz
Poland	Szpital Wojewodzki w Lomzy im. Kardynala S. Wyszynskiego	Lomza
Poland	Olsztynski Osrodek Onkologiczny "KOPERNIK"	Olsztyn
Poland	Szpital Rejonowy im. dr J. Rostka w Raciborzu	Raciborz
Poland	Wojewodzki Szpital Specjalistyczny im. J. Korczaka	Slupsk
Poland	Centrum Onkologii - Instytut im. Marii Sklodowskiej - Curie	Warszawa
Poland	NZOZ Magodent - Centrum Medczyne Ostrobramska	Warszawa
Romania	Spitalul Judetean de Urgenta "Dr. Constantin Opris" Baia-Mare [Oncologie Medicala]	Baia-Mare
Romania	Institutul Oncologic "Prof. Dr. Alex. Trestioreanu" [Sectia Clinica Radioterapie II]	Bucuresti
Romania	Spitalul Clinic CF nr.2 Bucuresti [Oncologie Medicala]	Bucuresti
Romania	Spitalul Universitar de Urgenta Bucuresti	Bucuresti
Romania	Spitalul Universitar de Urgenta Elias [Oncologie Medicala]	Bucuresti
Romania	Oncolab - Oncology Center Craiova	Craiova
Romania	Institutul Regional de Oncologia	Iasi
Romania	Spitalul Municipal Onesti [Sectia Oncologie Medicala]	Onesti
Romania	Spitalul Clinic Judetean Mures	Tg Mures
Romania	Oncomed SRL	Timisoara
Russian Federation	GUZ Arkhangelsk Regional Clinical Oncological Dispensary	Arkhangelsk
Russian Federation	Ivanovo Regional Oncological Dispensary [Chemotherapy]	Ivanovo
Russian Federation	GAUZ Republic Clinical Oncology Dispensary of Ministry of Health of Republic Tatarstan	Kazan
Russian Federation	GOU VPO Krasnoyarsk State Medical University n.a. prof. V.F.	Krasnoyarsk
Russian Federation	GUZ Lipetsk Regional Oncology Dispensary [General Oncology]	Lipetsk
Russian Federation	GUZ Regional Oncology Dispensary #2	Magnitogorsk
Russian Federation	Russian Cancer Research Center	Moscow
Russian Federation	SBHI of Moscow City Oncology Clinical Hospital #62	Moscow
Russian Federation	MBUZ City Clinical Hospital #1	Novosibirsk
Russian Federation	FGBU Medical Radiology Scientific Center	Obninsk
Russian Federation	GUZ Perm Regional Oncology Dispensary	Perm
Russian Federation	GUZ Pyatigorsk Oncology Dispensary [Outpatient Department]	Pyatigorsk
Russian Federation	GOU VPO - Ryazan State Med. Univer. n.a. I.I.Pavlov based Ryazan Regio	Ryazan
Russian Federation	City Oncology Dispensary	Saint Petersburg
Russian Federation	GOU VPO Saint-Petersburg State Medical University n.a. acad.	Saint Petersburg
Russian Federation	St. Petersburg Clinical Oncology Dispesary - 3rd Gynecology D	Saint Petersburg
Russian Federation	GUZ "Leningrad Regional Oncology Dispensary"	Saint-Petersburg
Russian Federation	GUZ Samara Regional Clinical Oncology Dispensary	Samara
Russian Federation	FGU Research Institute of Oncology n.a. N.N.Petrov of Rosmed	St. Petersburg
Russian Federation	Stavropol Regional Clinical Oncology Dispensary	Stavropol
Russian Federation	GBUZ - Clinical Oncology Dispensary of MoH of Republic Bahkortostan	Ufa
Russian Federation	GUZ Republican Clinical Oncological Dispensary of public	Ufa
Ukraine	Komunalnyi "Cherkaskyi oblasnyi onkolohichnyi dyspanser" Cherkaskoi oblasnoi rady, oblasnyi onkokhimioterapevtychnyi tsentr, m. Cherkasy	Cherkasy
Ukraine	Komunalnyi likuvalno-profilaktychnyi zaklad "Chernigivskyi	Chernigiv
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	Odessa
Ukraine	Poltavskyi oblasnyi klinichnyi onkolohichnyi dyspanser Pol	Poltava
Ukraine	Zakarpatskyi oblasnyi klinichnyi onkodyspanser	Uzhgorod
United States	Anniston Oncology/Regional Medical Center	Anniston	Alabama
United States	Palm Beach Institute of Hematology and Oncology	Boynton Beach	Florida
United States	Wellmont Medical Associates-Oncology and Hematology	Bristol	Tennessee
United States	Charleston Cancer Center	Charleston	South Carolina
United States	Charleston Hematology Oncology	Charleston	South Carolina
United States	Compassionate Cancer Care Medical Group Inc	Corona	California
United States	Cancer Specialists of South Texas, P.A.	Corpus Christi	Texas
United States	Denver Health and Hospital Authority	Denver	Colorado
United States	Duke University Medical Center	Durham	North Carolina
United States	Deaconess Clinic Downtown	Evansville	Indiana
United States	Compassionate Cancer Centre Medical Group	Fountain Valley	California
United States	The John R Marsh Cancer Center	Hagerstown	Maryland
United States	Kentucky Cancer Clinic	Hazard	Kentucky
United States	Genesis Cancer Centre	Hot Springs	Arkansas
United States	Baptist Cancer Institute	Jacksonville	Florida
United States	American Institute of Research	Los Angeles	California
United States	Tri-County Hematology and Oncolgy Associates Inc.	Massillon	Ohio
United States	Signal Point Clinical Research Center LLC	Middletown	Ohio
United States	Facey Medical Group	Mission Hills	California
United States	Northwest Alabama Cancer Center	Muscle Shoals	Alabama
United States	Floyd Memorial Cancer Center of Indiana	New Albany	Indiana
United States	Northern Utah Associates Hematology / Oncology	Ogden	Utah
United States	Compassionate Cancer Care Medical Group	Riverside	California
United States	Northwest Medical Specialties	Tacoma	Washington
United States	The University of Texas Health Center	Tyler	Texas
United States	American Institute of Research	Whittier	California
United States	Piedmont Hematology Oncology Associates PA	Winston-Salem	North Carolina
United States	Fallon Clinic at Worcester Medical Center	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Helsinn Healthcare SA	Parexel

Countries where clinical trial is conducted

United States,  Argentina,  Belarus,  Brazil,  Bulgaria,  Croatia,  Germany,  Hungary,  India,  Italy,  Mexico,  Poland,  Romania,  Russian Federation,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Patients With Complete Response (CR) Defined as no Emesis, no Rescue Medication, at Cycle 1		25-120 hours	No
Secondary	Percentage of Patients With Complete Response (CR) Defined as no Emesis, no Rescue Medication at Cycle 1		0-24 hours	No
Secondary	Percentage of Patients With Complete Response (CR) Defined as no Emesis, no Rescue Medication, at Cycle 1		0-120 hours	No