Clinical trial NCT02517021: A Safety Study of Intravenous Pro-Netupitant and Palonosetron Combination for the Prevention of Nausea and Vomiting
Official title: A Phase 3, Multicenter, Randomized, Double-blind, Active Control Study to Evaluate the Safety and Efficacy of IV Pro-netupitant/Palonosetron (260 mg/0.25 mg) Combination for the Prevention of Chemotherapy-induced Nausea and Vomiting in Repeated Chemotherapy Cycles in Patients Receiving Highly Emetogenic Chemotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chemotherapy-Induced Nausea and Vomiting
Lead sponsor: Helsinn Healthcare SA
Sponsor class: INDUSTRY
Collaborators: name: PSI CRO
First posted: 2015-08-06
Enrollment: 405
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: NEPA-15-18 is a clinical study assessing safety of pro-netupitant and palonosetron, two antiemetic drugs, given with oral dexamethasone. The objective of the study is to evaluate if pro-netupitant and palonosetron are safe when administered to prevent nausea and vomiting after administration of repeated cycles of chemotherapy.


Eligibility criteria: Inclusion Criteria:

Cycle 1

* Signed written informed consent
* Histologically or cytologically confirmed solid tumor malignancy.
* Naïve to cytotoxic chemotherapy. Previous biological or hormonal therapy will be permitted.
* Scheduled to receive at least 4 repeated consecutive cycles of the following highly emetogenic reference chemotherapies (HEC), alone or in combination with other chemotherapeutic agents on Day 1: cisplatin administered as a single IV dose of ≥ 70 mg/m2; cyclophosphamide ≥1500 mg/m2; carmustine (BCNU) \>250mg/m2; dacarbazine (DTIC); mechloretamine (nitrogen mustard)
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2 .
* If a patient is female, she shall be of non-childbearing potential or of childbearing potential using reliable contraceptive measures and having a negative urine pregnancy test.
* Hematologic and metabolic status adequate for receiving an highly emetogenic regimen based on laboratory criteria (Total Neutrophils,Platelets, Bilirubin, Liver enzymes, Serum Creatinine or Creatinine Clearance)
* Able to read, understand, follow the study procedure and complete patient diary.

Cycles 2 to 4:

The following inclusion criteria must be checked prior to inclusion at each repeated cycle:

* Participation in the study during the next cycle of chemotherapy is considered appropriate by the Investigator and does not pose unwarranted risk to the patient.
* Scheduled to receive the same chemotherapy regimen as Cycle 1 or one of the reference chemotherapies as defined in Inclusion criterion 5 for Cycle 1.
* If a patient is female, she shall be of non--childbearing potential or of childbearing potential using reliable contraceptive measures and having a negative urine pregnancy test.
* Adequate hematologic and metabolic status according to the Investigator's opinion.

Exclusion Criteria:

Cycle 1

* Lactating woman.
* Active infection or uncontrolled disease except for malignancy that may pose unwarranted risks in administering the study drugs to the patient.
* Current use of illicit drugs or current evidence of alcohol abuse.
* Scheduled to receive moderately or highly emetogenic chemotherapies from Day 2 to Day 5.
* Received or is scheduled to receive radiation therapy to the abdomen or the pelvis within 1 week prior to the start of the reference chemotherapy administration on Day 1 or between Days 1 to 5.
* Any vomiting, retching, or nausea (grade ≥ 1 as defined by National Cancer Institute) within 24 hours prior to the start of the reference chemotherapy administration on Day 1.
* Symptomatic primary or metastatic CNS malignancy.
* Known hypersensitivity or contraindication to 5-HT3 receptor antagonists, to dexamethasone or to NK-1 receptor antagonists.
* Known contraindication to the IV administration of 50 mL 5% glucose solution.
* Previously received an NK-1 receptor antagonist.
* Participation in a previous clinical trial involving IV pro-netupitant or oral netupitant administered alone or in combination with palonosetron.
* Any investigational drugs (other than those given in this study) taken within 4 weeks prior to Day 1, and/or is scheduled to receive any investigational drug during the present study.
* Systemic corticosteroid therapy at any dose within 72 hours prior to the start of reference chemotherapy administration on Day 1. Topical and inhaled corticosteroids are permitted.
* 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 within 1 week prior to Day 1: terfenadine, cisapride, astemizole, pimozide.
* Received within 4 weeks prior to Day 1 or scheduled to receive any CYP3A4 inducer.
* Any medication with known or potential antiemetic activity within 24 hours prior to the start of reference chemotherapy administration on Day 1 of Cycle 1, including but not limited to 5-HT3 receptor antagonists and NK-1 receptor antagonists
* History or predisposition to cardiac conduction abnormalities, except for incomplete right bundle branch block
* History of Torsade de Point or known history of risk factors for Torsade de Point (heart failure, hypokalemia, family history of Long QT Syndrome).
* Severe cardiovascular diseases diagnosed within 3 months prior to Day 1 of first cycle, including myocardial infarction, 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.

Cycles 2 to 4:

The following exclusion criteria must be checked prior to inclusion in each repeated cycle:

* Lactating woman.
* Active infection or uncontrolled disease except for malignancy that may pose unwarranted risks in administering the study drugs to the patient.
* Started any of the restricted medications.
* Any vomiting, retching, or nausea (grade ≥ 1 as defined by National Cancer Institute) within 24 hours prior to the start of reference chemotherapy administration on Day 1.
* Received or is scheduled to receive radiation therapy to the abdomen or the pelvis within 1 week prior to the start of the reference chemotherapy administration on Day 1 or between Days 1 to 5.
* Symptomatic primary or metastatic CNS malignancy.

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 14 weeks assuming a maximum of 4 chemotherapy cycles given every 3 weeks.
Secondary outcomes:
measure: Percentage of Patients With Complete Response (CR) Defined as no Emesis, no Rescue Medication, in the Acute Phase
timeFrame: 0-24 hours
measure: Percentage of Patients With Complete Response (CR) Defined as no Emesis, no Rescue Medication, in the Delayed Phase
timeFrame: >24-120 hours
measure: Percentage of Patients With Complete Response (CR) Defined as no Emesis, no Rescue Medication, in the Overall Phase
timeFrame: 0-120 hours
measure: Percentage of Patients With no Emetic Episodes in the Acute Phase
timeFrame: 0-24 hours
measure: Percentage of Patients With no Emetic Episodes in the Delayed Phase
timeFrame: >24-120 hours
measure: Percentage of Patients With no Emetic Episodes in the Overall Phase
timeFrame: 0-120 hours
measure: Percentage of Patients With no Significant Nausea (VAS <25 mm) During the Acute Phase
timeFrame: 0-24 hours
measure: Percentage of Patients With no Significant Nausea (VAS <25 mm) During the Delayed Phase
timeFrame: >24-120 hours
measure: Percentage of Patients With no Significant Nausea (VAS <25 mm) During the Overall Phase
timeFrame: 0-120 hours
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: Sarcoma Oncology Center
state: California
city: Whittier
country: United States
facility: The Oncology Institute of Hope and Innovation
state: California
city: Grand Junction
country: United States
facility: St. Mary's Medical Center
state: Colorado
city: Miami
country: United States
facility: Well Pharma Medical Research Corporation
state: Florida
city: Peoria
country: United States
facility: Illinois CancerCare
state: Illinois
city: Bloomington
country: United States
facility: Indiana University Health Bloomington
state: Indiana
city: Alexandria
country: United States
facility: Christus St. Frances Cabrini Hospital
state: Louisiana
city: East Setauket
country: United States
facility: North Shore Hematology Oncology Associates PC
state: New York
city: Canton
country: United States
facility: Gabrail Cancer Center Research
state: Ohio
city: Germantown
country: United States
facility: West Cancer Center
state: Tennessee
city: Knoxville
country: United States
facility: Provision Center for Biomedical Research
state: Tennessee
city: Graz
country: Austria
facility: University Hospital Graz, Department of Internal Medicine
city: Krems
country: Austria
facility: Krems Country Hospital
city: Linz
country: Austria
facility: Hospital Elisabethinen Linz GmbH, Internal Department #1 - Hemato-Oncology
city: Linz
country: Austria
facility: General Hospital Linz GmbH, Internal Medicine Department #3 - Center for Hematology and Medical Oncology
city: St. Poelten
country: Austria
facility: University Hospital St. Poelten,1st Medical Department
city: Osijek
country: Croatia
facility: Clinical Hospital Centre Osijek
city: Varazdin
country: Croatia
facility: General Hospital Varazdin
city: Zagreb
country: Croatia
facility: Clinical Hospital Center "Sestre milosrdnice"
city: Zagreb
country: Croatia
facility: University Hospital Centre Zagreb "Jordanovac"
city: Brno
country: Czechia
facility: University Hospital Brno. Clinic of Pulmonary Diseases and Tuberculosis
city: Brno
country: Czechia
facility: University Hospital
city: Novy Jicin
country: Czechia
facility: Hospital Novy Jicin, Department of Oncology
city: Prague
country: Czechia
facility: Thomayer's Hospital, Clinic of Pneumology
city: Prague
country: Czechia
facility: Hospital Na Bulovce
city: Usti nad Labem
country: Czechia
facility: Masaryk's Hospital Usti nad Labem, Oncology Dept
city: Bielefeld
country: Germany
facility: Onkoligische Schwerpunktpraxis Bielefeld
city: Hamburg
country: Germany
facility: OncoResearch Lerchenfeld GmbH
city: Hannover
country: Germany
facility: Hannover Medical School
city: Leipzig
country: Germany
facility: Universitaetsklinikum Leipzig; Universitaeres Krebszentrum (UCCL)
city: München
country: Germany
facility: Staedtisches Klinikum Muenchen GmbH; Klinikum N euperlach
city: Ashkelon
country: Israel
facility: Barziali Medical Center, Oncology Unit
city: Beer Sheva
country: Israel
facility: Soroka University Medical Center,Oncology division
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Avellino
country: Italy
facility: S. G. Moscati Hospital, Medical Oncology Division
city: Meldola
country: Italy
facility: cientific Institute of Romagna for the Study and Treatment of Cancer (IRST), IRCCS
city: Milan
country: Italy
facility: National Cancer Institute, IRCCS, Medical Oncology Department
city: Monza
country: Italy
facility: Azienda Socio Sanitaria Territoriale-Monza (ASST-Monza) - Oncology Department
city: Potenza
country: Italy
facility: Regional Hospital "San Carlo"
city: Vimercate
country: Italy
facility: Local Healthcare Company of Vimercate (ASST Vimercate)
city: Gdynia
country: Poland
facility: Provincial Hospitals in Gdynia Sp. z o.o. (LLC)
city: Poznan
country: Poland
facility: Lord's Transfiguration Teaching Hospital, Department of Chemotherapy
city: Prabuty
country: Poland
facility: Specialist Hospital in Prabuty Sp. z o .o. (LLC), Department of Pulmonology
city: Tarnobrzeg
country: Poland
facility: Zofia Zamoyska nee Tarnowska Provincial Hospital in Tarnobrzeg
city: Torun
country: Poland
facility: Ludwik Rydygier Provincial Hospital
city: Warsaw
country: Poland
facility: Maria Sklodowska-Curie Institute of Oncology, Department of Lung and Thoracic Cancers
city: Warsaw
country: Poland
facility: MAGODENT Sp. z o .o. (LLC), Branch No. 4, Department of Clinical Oncology/Chemotherapy
city: Belgrade
country: Serbia
facility: Clinical Center of Serbia, Clinic of Pulmonology
city: Belgrade
country: Serbia
facility: Clinical Hospital Center Bezanijska Kosa, Clinic of Oncology
city: Belgrade
country: Serbia
facility: Institute of Oncology and Radiology of Serbia, Clinic of Medical Oncology
city: Belgrade
country: Serbia
facility: Military Medical Academy
city: Sremska Kamenica
country: Serbia
facility: Institute of Pulmonary Diseases of Vojvodina, Pulmonary Oncology Clinic
city: Sremska Kamenica
country: Serbia
facility: Oncology Institute of Vojvodina
city: George
country: South Africa
facility: GVI Outeniqua Oncology Unit
city: Johannesburg
country: South Africa
facility: Medical Oncology Centre of Rosebank
city: Sevilla
country: Spain
facility: Hospital Nuestra Senora de Valme
state: Andalucia
city: Avila
country: Spain
facility: Our Lady of Sonsoles Hospital
city: Madrid
country: Spain
facility: Hospital Puerta de Hierro
city: Madrid
country: Spain
facility: Hospital La Paz, Oncology Department
city: Madrid
country: Spain
facility: University Hospital Quiron Madrid, Department of Oncology
city: Chernivtsi
country: Ukraine
facility: Chernivtsi Regional Clinical Oncology Center, Day Care Unit
city: Dnipropetrovsk
country: Ukraine
facility: Clinical Oncology Center, Department of Chemotherapy
city: Dnipropetrovsk
country: Ukraine
facility: Dnipropetrovsk City Multispecialty Clinical Hospital #4, Department of Chemotherapy
city: Ivano-Frankivsk
country: Ukraine
facility: Regional Clinical Oncology Center, Chemotherapy Department
city: Kharkiv
country: Ukraine
facility: S.P. Hryhoriev Institute of Medical Radiology, Department of Chemotherapy
city: Kharkiv
country: Ukraine
facility: Kharkiv Regional Clinical Oncology Center, Chemotherapy Department #1
city: Khmelnytskyi
country: Ukraine
facility: Khmelnytskyi Regional Oncology Center, Surgery Department #1
city: Kryvyi Rih
country: Ukraine
facility: Kryvyi Rih Oncology Center, Department of Chemotherapy
city: Lviv
country: Ukraine
facility: Lviv State Regional Treatment and Diagnostics Oncology Center, Department of Chemotherapy
city: Ternopil
country: Ukraine
facility: Ternopil Regional Public Clinical Oncology Center
city: Uzhhorod
country: Ukraine
facility: LTD UNIMED Adjara
city: Uzhhorod
country: Ukraine
facility: Zakarpattia Regional Clinical Oncology Center, Department of Chemotherapy
city: Vinnytsia
country: Ukraine
facility: Vinnytsia Regional Clinical Oncology Center, Department of Chemotherapy
city: Zaporizhia
country: Ukraine
facility: Zaporizhia Regional Clinical Oncology Center, Thoracic Department
Study officials:
References:
citation: Schwartzberg L, Roeland E, Andric Z, Kowalski D, Radic J, Voisin D, Rizzi G, Navari R, Gralla RJ, Karthaus M. Phase III safety study of intravenous NEPA: a novel fixed antiemetic combination of fosnetupitant and palonosetron in patients receiving highly emetogenic chemotherapy. Ann Oncol. 2018 Jul 1;29(7):1535-1540. doi: 10.1093/annonc/mdy169.