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

Phase 3
Completed
Conditions
Chemotherapy-Induced Nausea and Vomiting
Interventions
Registration Number
NCT01376297
Lead Sponsor
Helsinn Healthcare SA
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
413
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)

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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.
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Aprepitant and Palonosetron plus dexamethasoneDexamethasoneOral 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.
Netupitant and Palonosetron plus dexamethasoneNetupitant and PalonosetronOral netupitant/palonosetron (300 mg/0.50 mg) hard capsule (on Day 1) with oral dexamethasone prior to each scheduled chemotherapy cycle
Aprepitant and Palonosetron plus dexamethasoneAprepitantOral 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.
Netupitant and Palonosetron plus dexamethasoneDexamethasoneOral netupitant/palonosetron (300 mg/0.50 mg) hard capsule (on Day 1) with oral dexamethasone prior to each scheduled chemotherapy cycle
Aprepitant and Palonosetron plus dexamethasonePalonosetronOral 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.
Primary Outcome Measures
NameTimeMethod
Percentage of Patients With Adverse EventsParticipants 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

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.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (75)

MD Anderson Cancer Center

🇺🇸

Houston, Texas, United States

Veterans Administration New Jersey Health Care System

🇺🇸

East Orange, New Jersey, United States

East Valley Hematology and Oncology Medical Group

🇺🇸

Burbank, California, United States

Hematology Oncology Associates of Rockland

🇺🇸

Nyack, New York, United States

Cancer Center at Memorial Hospital of RI

🇺🇸

Pawtucket, Rhode Island, United States

COC - Vratsa Dept. of Palliative Care

🇧🇬

Vratsa, Bulgaria

Universitaetsklinikum Carl Gustav Carus

🇩🇪

Dresden, Germany

Gemeinschaftspraxis, Dr. Med O.Brundler und B.Heinreich, PD Dr. med M.Bangerter Fachärzte für Innere Medizin, Hämatologie und internistische Onkologie

🇩🇪

Augsburg, Germany

Krankenhaus, Maria Hilf, St. Franziskus Innere Medizin

🇩🇪

Mönchengladbach, Germany

Bekes Megyei Kepviselo-testulet Pandy Kalman Korhaz

🇭🇺

Gyula, Hungary

Praxis für Innere Medizin, Hämatologie und Internistische Onkologie

🇩🇪

Marburg, Germany

Praxis Fuer Interdisziplinaere Onkologie und Haematologie

🇩🇪

Freiburg, Germany

Dr. Bugyi Istvan Korhaz [Oncology]

🇭🇺

Szentes, Hungary

Kaposi Mor Oktato Korhaz [Klinikai Onkologiai Centrum]

🇭🇺

Kaposvár, Hungary

Bialostockie Centrum Onkologii im. M.Sklodowskiej-Curie im dr. E.Pileckiej z Pododdzialem Chemioterapii Dziennej

🇵🇱

Bialystok, Poland

Ginekologiczno-Położniczy Szpital Kliniczny UM w Poznaniu

🇵🇱

Poznan, Poland

Szpital Specjalistyczny

🇵🇱

Prabuty, Poland

GBUZ "Cheliabinsky Regional Oncology Dispensary"

🇷🇺

Chelyabinsk, Russian Federation

GUZ Leningradskiy Regional Oncology Dispensary

🇷🇺

St. Petersburg, Russian Federation

GBOU VPO "Saint-Petersburg State Medical University

🇷🇺

Saint-Petersburg, Russian Federation

GBUZ Tyumen Regional Oncology Dispensary

🇷🇺

Tyumen, Russian Federation

GUZ Tula Regional Oncological Dispensary [Oncology]

🇷🇺

Tula, Russian Federation

M.S Patel Cancer Hospital [Oncology]

🇮🇳

Gujarat, India

Apollo Speciality Hospital [Oncology]

🇮🇳

Madurai, India

American Institute of Research

🇺🇸

Los Angeles, California, United States

Northwest Alabama Cancer Center PC

🇺🇸

Muscle Shoals,, Alabama, United States

South Texas Comrehensive Cancer Centers

🇺🇸

Corpus Christi, Texas, United States

UMHAT "Dr. Georgi Stranski"

🇧🇬

Pleven, Bulgaria

Hematology and Oncology Associates, Inc.

🇺🇸

Canton, Ohio, United States

Spartanburg Regional Health Services

🇺🇸

Spartanburg, South Carolina, United States

COC - Veliko Tarnovo Dept. Medical Oncology

🇧🇬

Tarnovo, Bulgaria

Tri-County Hematology & Oncology Associates, Inc

🇺🇸

Massillon, Ohio, United States

Complex Oncology Center - Shumen Ltd. [Oncology]

🇧🇬

Shumen, Bulgaria

Charite - Campus Benjamin Franklin (CBF)

🇩🇪

Berlin, Germany

Országos Onkológiai Intézet, B. Belgyógyászati Osztály

🇭🇺

Budapest, Hungary

Specialized Hospital for Active Treatment in Oncology "Dr. Marko Markov" Varna

🇧🇬

Varna, Bulgaria

Fakultni nemocnice v Motole

🇨🇿

Praha 5, Czech Republic

Nemocnice Na Homolce, Oddeleni klinicke onkologie

🇨🇿

Praha 5, Czech Republic

Nemocnice Znojmo, p.o.

🇨🇿

Znojmo, Czech Republic

Oblastni nemocnice Mlada Boleslav a.s., Onkologie

🇨🇿

Mlada Boleslav, Czech Republic

AVICENNUS s.r.o. Onkologie Nymburk

🇨🇿

Nymburk, Czech Republic

Medizinische Hochschule, Zentrum für Innere Medizin, Klinik für Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation

🇩🇪

Hannover, Germany

Borsod-Abaúj-Zemplén Megyei Kórház és Egyetemi Oktatók

🇭🇺

Miskolc, Hungary

Acharya Harihara Regional Cancer Centre [Oncology]

🇮🇳

Cuttack, India

Fejér Megyei Szent György Kórház [Onkológiai Osztály]

🇭🇺

Székesfehérvár, Hungary

Centrum Onkologii Ziemi Lubelskiej im.Sw.Jana z Dukli III Oddzial Onkologii Ginekologicznej, Radioterapii I Chemioterapii

🇵🇱

Lublin, Poland

Kumaran Hospital PVT Ltd

🇮🇳

Chennai, India

Dr.Rai Memorial Medical centre

🇮🇳

Chennai, India

Research Unit, The Karnatak cancer therapy & Research Instit

🇮🇳

Hubli, India

S.M.S College And Hospital

🇮🇳

Jaipur, India

Lucknow Cancer Institute [Oncology]

🇮🇳

Uttar Pradesh, India

King George Hospital [Medical Oncology]

🇮🇳

Visakhapatnam, India

FBUZ Privolzhsky District Medical Center of FMBA

🇷🇺

Novgorod, Russian Federation

GAUZ Republican Clinical Oncology Dispensary of Minzdrav of Republic of Tatarstan

🇷🇺

Kazan, Russian Federation

Szpital Kliniczny Przemienienia Panskiego UM w Poznaniu

🇵🇱

Poznan, Poland

Wielkopolskie Centrum Onkologii im. M. Sklodowskiej-Curie i Onkologii Ginekologicznej

🇵🇱

Poznan, Poland

Szpital Rejonowy im. dr J. Rostka w Raciborzu

🇵🇱

Raciborz, Poland

Non-State healthcare Indtitution Central Clinical Hospital # 2 named after N.A. Semashko OAO "RZhD"

🇷🇺

Moscow, Russian Federation

Regional GUZ Orlovskiy Oncological Dispensary

🇷🇺

Orel, Russian Federation

GBUZ Republican Clinical Oncology Dispensary of Minzdrav of Republic of Bashkortostan

🇷🇺

Ufa, Russian Federation

Clinical Hospital Center Bezanijska Kosa

🇷🇸

Belgrade, Serbia

Institute of oncology and radiology of Serbia

🇷🇸

Beograd, Serbia

Chernivtsi Regional Cancer Hospital [Outpatient Department]

🇺🇦

Chernivtsi, Ukraine

Komunalnyi zaklad Miska bahatoprofilna klinichna likarnia #4

🇺🇦

Dnipropetrovks, Ukraine

Clinical Center Kragujevac

🇷🇸

Kragujevac, Serbia

KZ MKL19, MOTsr, vd khimter [viddilennia khimioterapii]

🇺🇦

Dnipropetrovsk, Ukraine

KKLPZ DnOPTsr [radio vd#3]

🇺🇦

Donetsk, Ukraine

Medizinisches Versorgungszentrum für Hämatologie und Tumorerkrankungen, HIV/AIDS und Hepatitiden

🇩🇪

Berlin, Germany

St. Johannes Hospital Medizinische Klinik II, Hämatologie, Onkologie und klinische Immunologie

🇩🇪

Duisburg, Germany

OncoPRO GbR Dr. R. Dengler, Dr. A. Kröber

🇩🇪

Regensburg, Germany

Ärzteforum Hennigsdorf

🇩🇪

Hennigsdorf, Germany

DU IMR AMNU [vd khemter]

🇺🇦

Kharkiv, Ukraine

Poltavskyi oblasnyi klinichnyi onkolohichnyi dyspanser Pol

🇺🇦

Poltava, Ukraine

ZaOKOD [abdom vd]

🇺🇦

Zaporizhia, Ukraine

Zakarpatskyi oblasnyi klinichnyi onkodyspanser [viddilennia

🇺🇦

Uzhgorod, Ukraine

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