A 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, Unbalanced (3:1) Active Control Study to Assess the Safety and Describe the Efficacy of Netupitant and Palonosetron for the Prevention of Chemotherapy-induced Nausea and Vomiting in Repeated Chemotherapy Cycles.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01376297
• Other study ID #: NETU-10-29
• Status: Completed
• Phase: Phase 3
• First received: June 16, 2011
• Last updated: November 6, 2014
• Start date: July 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 AdministrationUnited States: Institutional Review BoardGermany: Federal Institute for Drugs and Medical DevicesHungary: National Institute of PharmacyCzech Republic: Ethics CommitteeCzech Republic: State Institute for Drug ControlPoland: Ministry of HealthPoland: Ethics CommitteeSerbia and Montenegro: Agency for Drugs and Medicinal DevicesUkraine: Ethics CommitteeUkraine: Ministry of HealthRussia: Pharmacological Committee, Ministry of HealthRussia: Ethics CommitteeBulgaria: Bulgarian Drug AgencyBulgaria: Ethics committeeIndia: Central Drugs Standard Control OrganizationIndia: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

NETU-10-29 is a clinical study assessing safety of netupitant and palonosetron, two antiemetic drugs, both given with oral dexamethasone. The objective of the study is to evaluate if netupitant and palonosetron are safe when administered to prevent nausea and vomiting after administration of repeated cycles of chemotherapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 413
• Est. primary completion date: September 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Signed written informed consent.

• Naïve to cytotoxic chemotherapy. Previous biological or hormonal therapy is permitted.

• Diagnosed with a malignant tumor.

• If scheduled to receive repeated consecutive courses of chemotherapy, a single dose of one or more of the following agents administered on Day 1 is allowed:

• Highly emetogenic chemotherapy: any I.V. dose of cisplatin, mechlorethamine, streptozocin, cyclophosphamide more or equal to 1500 mg/m2, carmustine, dacarbazine;

• Moderately emetogenic chemotherapy: any I.V. dose of oxaliplatin, carboplatin, epirubicin, idarubicin, ifosfamide, irinotecan, daunorubicin, doxorubicin, cyclophosphamide I.V. (less than 1500 mg/m2), cytarabine I.V. (more than 1 g/m2), azacidine, alemtuzumab, bendamustine, or clofarabine.

• If scheduled to receive combination regimens, the most emetogenic agent is to be given as first on Day 1 and the infusion must be completed within 6 hours.

• If scheduled to receive chemotherapy agents of minimal to low emetogenic potential, they are to be given on Day 1 following the most emetogenic agent or on any subsequent study day.

• 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)

Exclusion Criteria:

• If female, lactating or pregnant

• Current use of illicit drugs or current evidence of alcohol abuse.

• Scheduled to receive either 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).

• Scheduled to receive moderately or highly emetogenic chemotherapy from Day 2 to Day 5 following Day 1 chemotherapy administration.

• Active infection or uncontrolled disease except for malignancy that may pose unwarranted risks in administering the study drugs to the patient.

• Known hypersensitivity or contraindication to 5-HT3 receptor antagonists or dexamethasone.

• Previously received an 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. Topical and inhaled corticosteroids with a steroid dose of less or equal to 10 mg of prednisone daily or its equivalent are permitted. Non-study drug dexamethasone as pre-medication in patients scheduled to receive taxanes is allowed.

• 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: 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 within 3 months prior to Day 1, including myocardial infarction, unstable angina pectoris, significant valvular or pericardial disease, history of ventricular tachycardia, symptomatic Congestive Heart Failure 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 for 4 days such as systemic fungal infection or uncontrolled diabetes.

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, 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

• Aprepitant

• Palonosetron

• Dexamethasone

Locations

Country	Name	City	State
Bulgaria	UMHAT "Dr. Georgi Stranski"	Pleven
Bulgaria	Complex Oncology Center - Shumen Ltd. [Oncology]	Shumen
Bulgaria	COC - Veliko Tarnovo Dept. Medical Oncology	Tarnovo
Bulgaria	Specialized Hospital for Active Treatment in Oncology "Dr. Marko Markov" Varna	Varna
Bulgaria	COC - Vratsa Dept. of Palliative Care	Vratsa
Czech Republic	Oblastni nemocnice Mlada Boleslav a.s., Onkologie	Mlada Boleslav
Czech Republic	AVICENNUS s.r.o. Onkologie Nymburk	Nymburk
Czech Republic	Fakultni nemocnice v Motole	Praha 5
Czech Republic	Nemocnice Na Homolce, Oddeleni klinicke onkologie	Praha 5
Czech Republic	Nemocnice Znojmo, p.o.	Znojmo
Germany	Gemeinschaftspraxis, Dr. Med O.Brundler und B.Heinreich, PD Dr. med M.Bangerter Fachärzte für Innere Medizin, Hämatologie und internistische Onkologie	Augsburg
Germany	Charite - Campus Benjamin Franklin (CBF)	Berlin
Germany	Medizinisches Versorgungszentrum für Hämatologie und Tumorerkrankungen, HIV/AIDS und Hepatitiden	Berlin
Germany	Universitaetsklinikum Carl Gustav Carus	Dresden
Germany	St. Johannes Hospital Medizinische Klinik II, Hämatologie, Onkologie und klinische Immunologie	Duisburg
Germany	Praxis Fuer Interdisziplinaere Onkologie und Haematologie	Freiburg
Germany	Medizinische Hochschule, Zentrum für Innere Medizin, Klinik für Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation	Hannover
Germany	Ärzteforum Hennigsdorf	Hennigsdorf
Germany	Praxis für Innere Medizin, Hämatologie und Internistische Onkologie	Marburg
Germany	Krankenhaus, Maria Hilf, St. Franziskus Innere Medizin	Mönchengladbach
Germany	OncoPRO GbR Dr. R. Dengler, Dr. A. Kröber	Regensburg
Hungary	Országos Onkológiai Intézet, B. Belgyógyászati Osztály	Budapest
Hungary	Bekes Megyei Kepviselo-testulet Pandy Kalman Korhaz	Gyula
Hungary	Kaposi Mor Oktato Korhaz [Klinikai Onkologiai Centrum]	Kaposvár
Hungary	Borsod-Abaúj-Zemplén Megyei Kórház és Egyetemi Oktatók	Miskolc
Hungary	Fejér Megyei Szent György Kórház [Onkológiai Osztály]	Székesfehérvár
Hungary	Dr. Bugyi Istvan Korhaz [Oncology]	Szentes
India	Dr.Rai Memorial Medical centre	Chennai
India	Kumaran Hospital PVT Ltd	Chennai
India	Acharya Harihara Regional Cancer Centre [Oncology]	Cuttack
India	M.S Patel Cancer Hospital [Oncology]	Gujarat
India	Research Unit, The Karnatak cancer therapy & Research Instit	Hubli
India	S.M.S College And Hospital	Jaipur
India	Apollo Speciality Hospital [Oncology]	Madurai
India	Lucknow Cancer Institute [Oncology]	Uttar Pradesh
India	King George Hospital [Medical Oncology]	Visakhapatnam
Poland	Bialostockie Centrum Onkologii im. M.Sklodowskiej-Curie im dr. E.Pileckiej z Pododdzialem Chemioterapii Dziennej	Bialystok
Poland	Centrum Onkologii Ziemi Lubelskiej im.Sw.Jana z Dukli III Oddzial Onkologii Ginekologicznej, Radioterapii I Chemioterapii	Lublin
Poland	Ginekologiczno-Polozniczy Szpital Kliniczny UM w Poznaniu	Poznan
Poland	Szpital Kliniczny Przemienienia Panskiego UM w Poznaniu	Poznan
Poland	Wielkopolskie Centrum Onkologii im. M. Sklodowskiej-Curie i Onkologii Ginekologicznej	Poznan
Poland	Szpital Specjalistyczny	Prabuty
Poland	Szpital Rejonowy im. dr J. Rostka w Raciborzu	Raciborz
Russian Federation	GBUZ "Cheliabinsky Regional Oncology Dispensary"	Chelyabinsk
Russian Federation	GAUZ Republican Clinical Oncology Dispensary of Minzdrav of Republic of Tatarstan	Kazan
Russian Federation	Non-State healthcare Indtitution Central Clinical Hospital # 2 named after N.A. Semashko OAO "RZhD"	Moscow
Russian Federation	FBUZ Privolzhsky District Medical Center of FMBA	Novgorod
Russian Federation	Regional GUZ Orlovskiy Oncological Dispensary	Orel
Russian Federation	GBOU VPO "Saint-Petersburg State Medical University	Saint-Petersburg
Russian Federation	GUZ Leningradskiy Regional Oncology Dispensary	St. Petersburg
Russian Federation	GUZ Tula Regional Oncological Dispensary [Oncology]	Tula
Russian Federation	GBUZ Tyumen Regional Oncology Dispensary	Tyumen
Russian Federation	GBUZ Republican Clinical Oncology Dispensary of Minzdrav of Republic of Bashkortostan	Ufa
Serbia	Clinical Hospital Center Bezanijska Kosa	Belgrade
Serbia	Institute of oncology and radiology of Serbia	Beograd
Serbia	Clinical Center Kragujevac	Kragujevac
Ukraine	Chernivtsi Regional Cancer Hospital [Outpatient Department]	Chernivtsi
Ukraine	Komunalnyi zaklad Miska bahatoprofilna klinichna likarnia #4	Dnipropetrovks
Ukraine	KZ MKL19, MOTsr, vd khimter [viddilennia khimioterapii]	Dnipropetrovsk
Ukraine	KKLPZ DnOPTsr [radio vd#3]	Donetsk
Ukraine	DU IMR AMNU [vd khemter]	Kharkiv
Ukraine	Poltavskyi oblasnyi klinichnyi onkolohichnyi dyspanser Pol	Poltava
Ukraine	Zakarpatskyi oblasnyi klinichnyi onkodyspanser [viddilennia	Uzhgorod
Ukraine	ZaOKOD [abdom vd]	Zaporizhia
United States	East Valley Hematology and Oncology Medical Group	Burbank	California
United States	Hematology and Oncology Associates, Inc.	Canton	Ohio
United States	South Texas Comrehensive Cancer Centers	Corpus Christi	Texas
United States	Veterans Administration New Jersey Health Care System	East Orange	New Jersey
United States	MD Anderson Cancer Center	Houston	Texas
United States	American Institute of Research	Los Angeles	California
United States	Tri-County Hematology & Oncology Associates, Inc	Massillon	Ohio
United States	Northwest Alabama Cancer Center PC	Muscle Shoals,	Alabama
United States	Hematology Oncology Associates of Rockland	Nyack	New York
United States	Cancer Center at Memorial Hospital of RI	Pawtucket	Rhode Island
United States	Spartanburg Regional Health Services	Spartanburg	South Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Helsinn Healthcare SA	Parexel

Countries where clinical trial is conducted

United States,  Bulgaria,  Czech Republic,  Germany,  Hungary,  India,  Poland,  Russian Federation,  Serbia,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Patients With Adverse Events	This was a safety study where Adverse Events is the primary outcome (defined by the current ICH Guideline for Good Clinical Practice). Patients were randomized according to a 3:1 ratio (netupitant/palonosetron:aprepitant/palonosetron). No formal comparison was planned, the presence of a control in the same patient population helped interpret any unexpected safety finding in the experimental arm.The number of patients was estimated in order to have more than 100 patients treated with the netupitant/palonosetron comination for up to at least six cycles. Based on 100 patients, if a given 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 24 weeks assuming 6 chemotherapy cycles given every 4 weeks	No