Clinical trial NCT01376297: A Safety Study of Oral Netupitant and Palonosetron for the Prevention of Nausea and Vomiting
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chemotherapy-Induced Nausea and Vomiting
Lead sponsor: Helsinn Healthcare SA
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2011-06-20
Enrollment: 413
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.


Eligibility criteria: 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.

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