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

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.

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.

Study Overview

• Status: Completed
• Conditions: Chemotherapy-Induced Nausea and Vomiting
• Intervention / Treatment: Drug: Dexamethasone; Drug: Palonosetron; Drug: Netupitant and Palonosetron; Drug: Aprepitant

• Study Type: Interventional
• Enrollment (Actual): 413
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Pleven, Bulgaria, 5800
    • UMHAT "Dr. Georgi Stranski"
  • Shumen, Bulgaria, 9700
    • Complex Oncology Center - Shumen Ltd. [Oncology]
  • Tarnovo, Bulgaria, 5000
    • COC - Veliko Tarnovo Dept. Medical Oncology
  • Varna, Bulgaria, 9010
    • Specialized Hospital for Active Treatment in Oncology "Dr. Marko Markov" Varna
  • Vratsa, Bulgaria, 3000
    • COC - Vratsa Dept. of Palliative Care
• Czech Republic
  • Mlada Boleslav, Czech Republic, 293 50
    • Oblastni nemocnice Mlada Boleslav a.s., Onkologie
  • Nymburk, Czech Republic, 288 01
    • AVICENNUS s.r.o. Onkologie Nymburk
  • Praha 5, Czech Republic, 150 06
    • Fakultni nemocnice v Motole
  • Praha 5, Czech Republic, 150 30
    • Nemocnice Na Homolce, Oddeleni klinicke onkologie
  • Znojmo, Czech Republic, 669 02
    • Nemocnice Znojmo, p.o.
• Germany
  • Augsburg, Germany, 86150
    • Gemeinschaftspraxis, Dr. Med O.Brundler und B.Heinreich, PD Dr. med M.Bangerter Fachärzte für Innere Medizin, Hämatologie und internistische Onkologie
  • Berlin, Germany, 12200
    • Charite - Campus Benjamin Franklin (Cbf)
  • Berlin, Germany, 13347
    • Medizinisches Versorgungszentrum für Hämatologie und Tumorerkrankungen, HIV/AIDS und Hepatitiden
  • Dresden, Germany, 01307
    • Universitaetsklinikum Carl Gustav Carus
  • Duisburg, Germany, 47166
    • St. Johannes Hospital Medizinische Klinik II, Hämatologie, Onkologie und klinische Immunologie
  • Freiburg, Germany, 79106
    • Praxis Fuer Interdisziplinaere Onkologie und Haematologie
  • Hannover, Germany, 30625
    • Medizinische Hochschule, Zentrum für Innere Medizin, Klinik für Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation
  • Hennigsdorf, Germany, 16761
    • Ärzteforum Hennigsdorf
  • Marburg, Germany, 35037
    • Praxis für Innere Medizin, Hämatologie und Internistische Onkologie
  • Mönchengladbach, Germany, 41062
    • Krankenhaus, Maria Hilf, St. Franziskus Innere Medizin
  • Regensburg, Germany, 93053
    • OncoPRO GbR Dr. R. Dengler, Dr. A. Kröber
• Hungary
  • Budapest, Hungary, 1122
    • Országos Onkológiai Intézet, B. Belgyógyászati Osztály
  • Gyula, Hungary, 5700
    • Bekes Megyei Kepviselo-testulet Pandy Kalman Korhaz
  • Kaposvár, Hungary, 7400
    • Kaposi Mor Oktato Korhaz [Klinikai Onkologiai Centrum]
  • Miskolc, Hungary, 3501
    • Borsod-Abaúj-Zemplén Megyei Kórház és Egyetemi Oktatók
  • Szentes, Hungary, 6600
    • Dr. Bugyi Istvan Korhaz [Oncology]
  • Székesfehérvár, Hungary, 8000
    • Fejér Megyei Szent György Kórház [Onkológiai Osztály]
• India
  • Chennai, India, 600010
    • Kumaran Hospital PVT Ltd
  • Chennai, India, 600018
    • Dr.Rai Memorial Medical centre
  • Cuttack, India, 753007
    • Acharya Harihara Regional Cancer Centre [Oncology]
  • Gujarat, India, 388325
    • M.S Patel Cancer Hospital [Oncology]
  • Hubli, India, 580025
    • Research Unit, The Karnatak cancer therapy & Research Instit
  • Jaipur, India, 302016
    • S.M.S College And Hospital
  • Madurai, India, 625020
    • Apollo Speciality Hospital [Oncology]
  • Uttar Pradesh, India, 226001
    • Lucknow Cancer Institute [Oncology]
  • Visakhapatnam, India, 530002
    • King George Hospital [Medical Oncology]
• Poland
  • Bialystok, Poland, 15-027
    • Bialostockie Centrum Onkologii im. M.Sklodowskiej-Curie im dr. E.Pileckiej z Pododdzialem Chemioterapii Dziennej
  • Lublin, Poland, 20-090
    • Centrum Onkologii Ziemi Lubelskiej im.Sw.Jana z Dukli III Oddzial Onkologii Ginekologicznej, Radioterapii I Chemioterapii
  • Poznan, Poland, 60-535
    • Ginekologiczno-Położniczy Szpital Kliniczny UM w Poznaniu
  • Poznan, Poland, 60-569
    • Szpital Kliniczny Przemienienia Panskiego UM w Poznaniu
  • Poznan, Poland, 61-866
    • Wielkopolskie Centrum Onkologii im. M. Sklodowskiej-Curie i Onkologii Ginekologicznej
  • Prabuty, Poland, 82-550
    • Szpital Specjalistyczny
  • Raciborz, Poland, 47-400
    • Szpital Rejonowy im. dr J. Rostka w Raciborzu
• Russian Federation
  • Chelyabinsk, Russian Federation, 454087
    • GBUZ "Cheliabinsky Regional Oncology Dispensary"
  • Kazan, Russian Federation, 420029
    • GAUZ Republican Clinical Oncology Dispensary of Minzdrav of Republic of Tatarstan
  • Moscow, Russian Federation, 129128
    • Non-State healthcare Indtitution Central Clinical Hospital # 2 named after N.A. Semashko OAO "RZhD"
  • Novgorod, Russian Federation, 603001
    • FBUZ Privolzhsky District Medical Center of FMBA
  • Orel, Russian Federation, 302020
    • Regional GUZ Orlovskiy Oncological Dispensary
  • Saint-Petersburg, Russian Federation, 197022
    • GBOU VPO "Saint-Petersburg State Medical University
  • St. Petersburg, Russian Federation, 191104
    • GUZ Leningradskiy Regional Oncology Dispensary
  • Tula, Russian Federation, 300040
    • GUZ Tula Regional Oncological Dispensary [Oncology]
  • Tyumen, Russian Federation, 625041
    • GBUZ Tyumen Regional Oncology Dispensary
  • Ufa, Russian Federation, 450054
    • GBUZ Republican Clinical Oncology Dispensary of Minzdrav of Republic of Bashkortostan
• Serbia
  • Belgrade, Serbia, 11000
    • Clinical Hospital Center Bezanijska Kosa
  • Beograd, Serbia, 11000
    • Institute of Oncology and Radiology of Serbia
  • Kragujevac, Serbia, 34000
    • Clinical Center Kragujevac
• Ukraine
  • Chernivtsi, Ukraine, 58013
    • Chernivtsi Regional Cancer Hospital [Outpatient Department]
  • Dnipropetrovks, Ukraine, 49102
    • Komunalnyi zaklad Miska bahatoprofilna klinichna likarnia #4
  • Dnipropetrovsk, Ukraine, 49100
    • KZ MKL19, MOTsr, vd khimter [viddilennia khimioterapii]
  • Donetsk, Ukraine, 83092
    • KKLPZ DnOPTsr [radio vd#3]
  • Kharkiv, Ukraine, 61024
    • DU IMR AMNU [vd khemter]
  • Poltava, Ukraine, 36011
    • Poltavskyi oblasnyi klinichnyi onkolohichnyi dyspanser Pol
  • Uzhgorod, Ukraine, 88014
    • Zakarpatskyi oblasnyi klinichnyi onkodyspanser [viddilennia
  • Zaporizhia, Ukraine, 69040
    • ZaOKOD [abdom vd]
• United States
  • Alabama
    • Muscle Shoals,, Alabama, United States, 35661
      • Northwest Alabama Cancer Center PC
  • California
    • Burbank, California, United States, 91505
      • East Valley Hematology and Oncology medical Group
    • Los Angeles, California, United States, 90017
      • American Institute of Research
  • New Jersey
    • East Orange, New Jersey, United States, 07018
      • Veterans Administration New Jersey Health Care System
  • New York
    • Nyack, New York, United States, 10960
      • Hematology Oncology Associates of Rockland
  • Ohio
    • Canton, Ohio, United States, 44708
      • Hematology and Oncology Associates, Inc.
    • Massillon, Ohio, United States, 44646
      • Tri-County Hematology & Oncology Associates, Inc
  • Rhode Island
    • Pawtucket, Rhode Island, United States, 02860
      • Cancer Center at Memorial Hospital of RI
  • South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Regional Health Services
  • Texas
    • Corpus Christi, Texas, United States, 78405
      • South Texas Comrehensive Cancer Centers
    • Houston, Texas, United States, 77030-4009
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Netupitant and 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	Drug: Dexamethasone; Drug: Netupitant and Palonosetron
ACTIVE_COMPARATOR: Aprepitant and Palonosetron plus dexamethasone; Oral aprepitant hard capsule 125 mg (on Day 1) + 80 mg daily (for the following two days) and oral palonosetron soft capsule 0.50 mg (on Day 1) given with oral dexamethasone at each scheduled chemotherapy cycle.	Drug: Dexamethasone; Drug: Palonosetron; Drug: Aprepitant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Helsinn Healthcare SA
• Collaborators: Parexel

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (ACTUAL): September 1, 2012

Study Registration Dates

• First Submitted: June 16, 2011
• First Submitted That Met QC Criteria: June 17, 2011
• First Posted (ESTIMATE): June 20, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): November 17, 2014
• Last Update Submitted That Met QC Criteria: November 6, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Nausea; Vomiting; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Serotonin Agents; Serotonin Antagonists; Serotonin 5-HT3 Receptor Antagonists; Neurokinin-1 Receptor Antagonists; Dexamethasone; Palonosetron; Aprepitant
• Other Study ID Numbers: NETU-10-29