An Efficacy and Safety Study of Oral Netupitant and Palonosetron for the Prevention of Nausea and Vomiting
Chemotherapy-Induced Nausea and Vomiting
About this trial
This is an interventional prevention trial for Chemotherapy-Induced Nausea and Vomiting
Eligibility Criteria
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.
Sites / Locations
- Anniston Oncology/Regional Medical Center
- Northwest Alabama Cancer Center
- Genesis Cancer Centre
- Compassionate Cancer Care Medical Group Inc
- Compassionate Cancer Centre Medical Group
- American Institute of Research
- Facey Medical Group
- Compassionate Cancer Care Medical Group
- American Institute of Research
- Denver Health and Hospital Authority
- Palm Beach Institute of Hematology and Oncology
- Baptist Cancer Institute
- Deaconess Clinic Downtown
- Floyd Memorial Cancer Center of Indiana
- Kentucky Cancer Clinic
- The John R Marsh Cancer Center
- Fallon Clinic at Worcester Medical Center
- Duke University Medical Center
- Piedmont Hematology Oncology Associates PA
- Tri-County Hematology and Oncolgy Associates Inc.
- Signal Point Clinical Research Center LLC
- Charleston Cancer Center
- Charleston Hematology Oncology
- Wellmont Medical Associates-Oncology and Hematology
- Cancer Specialists of South Texas, P.A.
- The University of Texas Health Center
- Northern Utah Associates Hematology / Oncology
- Northwest Medical Specialties
- Instituto Oncológico de Córdoba - Sanatorio Aconcagua
- Hospital Italiano de Cordoba
- Clínica Universitaria Reina Fabiola (Universidad Católica de Córdoba)
- Centro Oncológico Integral (COI)
- Centro Oncologico de Integracion Regional (COIR)
- Instituto Médico CER [Oncology]
- Sanatorio Parque
- Centro Medico San Roque
- ISIS Clinica Especializada
- Bobruisk Interregional Oncological Dispensary
- Brest Regional Oncological Dispensary
- Gomel Regional Clinical Oncological Dispensary
- Minsk city Clinical Oncological Dispensary [Oncology]
- State institution N.N. Alexandrov Republican Scientific and Practical Center of Oncology and Medical Radiology
- Mogilev Regional Oncological Dispensary [Oncology]
- OXION-Medicina Oncológica
- Centro de Pesquisas Clínicas em Oncologia
- IPCEM - Centro de Ciências da Saúde - Universidade de Caxias
- Hospital Araújo Jorge
- Clinica de Neoplasias do Litoral
- Clinica De Oncologia De Porto Alegre S S Ltda
- Hospital Moinhos de Vento
- Instituto Ribeirãopretano de Combate ao Cancer
- Oncotrat Oncologia Medica Ltda [Oncology]
- Nucleo de Oncologia da Bahia
- Hospital Santa Cruz
- Casa de Saude Santa Marcelina
- SHATO "Sveti Mina"
- MHAT Dr. Tota Venkova [Oncology]
- Specialized Hospital for Active Treatment of Oncology
- UMHAT ""Dr. Georgi Stranski"" Dept. Medical Oncology
- UMHAT "Sveti Georgi" [Clinic of Oncology and Hematology]
- District Dispensery with Stationary - Sofia District
- UMHAT "Tsaritsa Yoanna - ISUL" Ltd.Medical Oncology Clinic
- Specialized Hospital for Active Treatment in Oncology
- Specialized Hospital for Active Treatment of Onclogy Diseases - Sofia City
- Complex Oncology Centre
- COC - Veliko Tarnovo Dept. Medical Oncology
- Comprehensive Cancer Center - Vratsa Dept. of Palliative Care
- Županijska bolnica Cakovec
- Klinicki bolnicki centar Osijek [Oncology]
- Opca bolnica Pula [Odjel za onklologiju]
- KBC Rijeka [Gastroenterology]
- Opca bolnica Varazdin [Odjel za hem.onko i klin.imun.]
- Opca Bolnica Zadal Ulica
- Klinički bolnički centar Zagreb [Oncology]
- Klinicka bolnica [Sestre milosrdnice]
- Klinika za tumore [Odjel za kemoter. i internisticku onkolog
- Klinik und Poliklinik für Onkologie und Hämatologie Universitatsmedizin Charite Mitte
- Gynäkologische Arztpraxis
- OncoResearch Lerchenfeld UG
- Schwerpktprxs gynäkolog Onkologie Prof. Dr. Diel, Dr. Gebert
- Rotkreuzklinikum [München]
- Tumorzentrum Munchen Sued - Städtisches Klinikum [Hämato-, Onkologie + Palliativmed]
- Staedtisches Krankenhaus Muenchen Neuperlach
- OncoPRO GbR Dr. R. Dengler, Dr. A. Kröber Gesellschaft für klinische Studien in der ambulanten Hämatologie und Onkologie
- Universitätsklinikum Tübingen
- Praxis Dr. G. Dresemann
- Onkologische Gemeinschaftspraxis Dr. med M. Perker / PF Dr. med M. Sandherr
- Semmelweis Egyetem Kútvölgyi Klinikai Tömb
- Fővárosi Önkormányzat Uzsoki utcai Kórház
- Petz Aladár Megyei Oktató Kórház [Onkoradiológiai Oszt
- Bács-Kiskun Megyei Önkormányzat Kórháza, Szegedi
- Borsod-Abaúj-Zemplén Megyei Kórház és Egyetemi Oktató Kórház
- Josa Andras Oktato Korhaz [Onkologiai Osztaly]
- Pécsi Tudományegyetem Klinikai Köpont
- Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz
- HCG - Multy Speciality Hospital
- Hemato-Oncology Clinic Ahmedabad Pvt Ltd
- Sujan Surgical Cancer Hospital and Amracvati Cancer Foundation
- Sri Venkateshwara Hospital [Medical Oncology]
- Apollo Speciality Hospital
- Dr. Kamahshi Memorial Hospital [Oncology]
- BIBI General Hospital & Cancer Centre [Oncology]
- Yashoda B-Block Hospital
- B.P.Poddar Hospital and Medical Research Ltd
- Apollo Gleneagles Hospitals Kolkata
- Shatabdhi Superspeciality Hospital
- Grant Medical Foundation - Ruby Hall Clinic
- City Cancer Centre [Surgical and Medical Oncology]
- Fondazione Poliambulanza Istituto Ospedaliero
- Ospedale Vito Fazzi, ASL Lecce
- Presidio Ospedaliero "Alessandro Manzoni", AO Provincia di Lecco
- Ospedale Sacro Cuore e Don Calabria - Negrar
- Ospedale S.Carlo di Potenza [U.O. di Oncologia Medica]
- Centro Oncologico De Chihuahua
- Hospital de Jesus
- Centro Medico Quirurgico
- OCA Hospital/Monterrey International Research Center
- Centro Regiomontano de Investigación Clínica
- Bialostockie Centrum Onkologii im. M.Sklodowskiej-Curie
- Wojewodzki Szpital Zespolony w Elblagu, Oddzial Onkologiczny
- Niepubliczny Specjalist. Onkol. Zaklad Opieki Zdrowotnej
- Wojewodzki Szpital Specjalistyczny im. M.Kopernika
- Szpital Wojewodzki w Lomzy im. Kardynala S. Wyszynskiego
- Olsztynski Osrodek Onkologiczny "KOPERNIK"
- Szpital Rejonowy im. dr J. Rostka w Raciborzu
- Wojewodzki Szpital Specjalistyczny im. J. Korczaka
- Centrum Onkologii - Instytut im. Marii Sklodowskiej - Curie
- NZOZ Magodent - Centrum Medczyne Ostrobramska
- Spitalul Judetean de Urgenta "Dr. Constantin Opris" Baia-Mare [Oncologie Medicala]
- Spitalul Universitar de Urgenta Elias [Oncologie Medicala]
- Spitalul Clinic CF nr.2 Bucuresti [Oncologie Medicala]
- Spitalul Universitar de Urgenta Bucuresti
- Institutul Oncologic "Prof. Dr. Alex. Trestioreanu" [Sectia Clinica Radioterapie II]
- Oncolab - Oncology Center Craiova
- Institutul Regional de Oncologia
- Spitalul Municipal Onesti [Sectia Oncologie Medicala]
- Spitalul Clinic Judetean Mures
- Oncomed SRL
- GUZ Arkhangelsk Regional Clinical Oncological Dispensary
- Ivanovo Regional Oncological Dispensary [Chemotherapy]
- GAUZ Republic Clinical Oncology Dispensary of Ministry of Health of Republic Tatarstan
- GOU VPO Krasnoyarsk State Medical University n.a. prof. V.F.
- GUZ Lipetsk Regional Oncology Dispensary [General Oncology]
- GUZ Regional Oncology Dispensary #2
- Russian Cancer Research Center
- SBHI of Moscow City Oncology Clinical Hospital #62
- MBUZ City Clinical Hospital #1
- FGBU Medical Radiology Scientific Center
- GUZ Perm Regional Oncology Dispensary
- GUZ Pyatigorsk Oncology Dispensary [Outpatient Department]
- GOU VPO - Ryazan State Med. Univer. n.a. I.I.Pavlov based Ryazan Regio
- City Oncology Dispensary
- GOU VPO Saint-Petersburg State Medical University n.a. acad.
- St. Petersburg Clinical Oncology Dispesary - 3rd Gynecology D
- GUZ "Leningrad Regional Oncology Dispensary"
- GUZ Samara Regional Clinical Oncology Dispensary
- FGU Research Institute of Oncology n.a. N.N.Petrov of Rosmed
- Stavropol Regional Clinical Oncology Dispensary
- GBUZ - Clinical Oncology Dispensary of MoH of Republic Bahkortostan
- GUZ Republican Clinical Oncological Dispensary of public
- Komunalnyi "Cherkaskyi oblasnyi onkolohichnyi dyspanser" Cherkaskoi oblasnoi rady, oblasnyi onkokhimioterapevtychnyi tsentr, m. Cherkasy
- Komunalnyi likuvalno-profilaktychnyi zaklad "Chernigivskyi
- Chmelnytskyi Regional Clinical Oncology Centre [Oncology]
- Komunalnyizaklad Miska bahatoprofilna klinichna likarnia #4
- Donetskyi oblasnyi protypukhlynnyi tsentr
- Kharkivskyi oblasnyi onkologichnyi klinichnyi tsentr
- Kyirskyi Miskyi klinichnyi onkolohichnyi tsentr
- KZ KOR Kyivskyi oblasnyi onkologichnyi dyspanser
- Lvivskyi derzhavnyi onkologichnyi regionalnyi likuvalno diahnostychyi tsentr
- Odeska oblasna klinichna likarnia
- Poltavskyi oblasnyi klinichnyi onkolohichnyi dyspanser Pol
- Zakarpatskyi oblasnyi klinichnyi onkodyspanser
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Experimental
Active Comparator
Experimental
Active Comparator
Netupitant and Palonosetron+dexamethasone-cycle 1
Palonosetron+dexamethasone-cycle 1
Netupitant and Palonosetron+dexamethasone-multicycle extension
Palonosetron+dexamethasone-multicycle extension
Oral netupitant/palonosetron (300 mg/0.50 mg) hard capsule with oral dexamethasone (12 mg), both given on Day 1, prior to each scheduled chemotherapy cycle
Oral palonosetron 0.50 mg (Aloxi) with oral dexamethasone (20 mg) both given on Day 1, prior to each scheduled chemotherapy cycle
Oral netupitant/palonosetron (300 mg/0.50 mg) hard capsule with oral dexamethasone (12 mg), both given on Day 1, prior to each scheduled chemotherapy cycle
Oral palonosetron 0.50 mg (Aloxi) with oral dexamethasone (20 mg) both given on Day 1, prior to each scheduled chemotherapy cycle