A Safety Study of Intravenous Pro-Netupitant and Palonosetron Combination for the Prevention of Nausea and Vomiting

Chemotherapy-Induced Nausea and Vomiting Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02517021
• Other study ID #: NEPA-15-18
• Status: Completed
• Phase: Phase 3
• Start date: November 2015
• Est. completion date: August 2016

Study information

• Verified date: June 2018
• Source: Helsinn Healthcare SA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 405
• Est. completion date: August 2016
• Est. primary completion date: August 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Chemotherapy-Induced Nausea and Vomiting
• Nausea
• Vomiting

Intervention

Drug:
• Pro-netupitant/Palonosetron

• Netupitant/Palonosetron

• Dexamethasone

Locations

Country	Name	City	State
Austria	University Hospital Graz, Department of Internal Medicine	Graz
Austria	Krems Country Hospital	Krems
Austria	General Hospital Linz GmbH, Internal Medicine Department #3 - Center for Hematology and Medical Oncology	Linz
Austria	Hospital Elisabethinen Linz GmbH, Internal Department #1 - Hemato-Oncology	Linz
Austria	University Hospital St. Poelten,1st Medical Department	St. Poelten
Croatia	Clinical Hospital Centre Osijek	Osijek
Croatia	General Hospital Varazdin	Varazdin
Croatia	Clinical Hospital Center "Sestre milosrdnice"	Zagreb
Croatia	University Hospital Centre Zagreb "Jordanovac"	Zagreb
Czechia	University Hospital	Brno
Czechia	University Hospital Brno. Clinic of Pulmonary Diseases and Tuberculosis	Brno
Czechia	Hospital Novy Jicin, Department of Oncology	Novy Jicin
Czechia	Hospital Na Bulovce	Prague
Czechia	Thomayer's Hospital, Clinic of Pneumology	Prague
Czechia	Masaryk's Hospital Usti nad Labem, Oncology Dept	Usti nad Labem
Germany	Onkoligische Schwerpunktpraxis Bielefeld	Bielefeld
Germany	OncoResearch Lerchenfeld GmbH	Hamburg
Germany	Hannover Medical School	Hannover
Germany	Universitaetsklinikum Leipzig; Universitaeres Krebszentrum (UCCL)	Leipzig
Germany	Staedtisches Klinikum Muenchen GmbH; Klinikum N euperlach	München
Israel	Barziali Medical Center, Oncology Unit	Ashkelon
Israel	Soroka University Medical Center,Oncology division	Beer Sheva
Israel	Rambam Health Care Campus	Haifa
Italy	S. G. Moscati Hospital, Medical Oncology Division	Avellino
Italy	cientific Institute of Romagna for the Study and Treatment of Cancer (IRST), IRCCS	Meldola
Italy	National Cancer Institute, IRCCS, Medical Oncology Department	Milan
Italy	Azienda Socio Sanitaria Territoriale-Monza (ASST-Monza) - Oncology Department	Monza
Italy	Regional Hospital "San Carlo"	Potenza
Italy	Local Healthcare Company of Vimercate (ASST Vimercate)	Vimercate
Poland	Provincial Hospitals in Gdynia Sp. z o.o. (LLC)	Gdynia
Poland	Lord's Transfiguration Teaching Hospital, Department of Chemotherapy	Poznan
Poland	Specialist Hospital in Prabuty Sp. z o .o. (LLC), Department of Pulmonology	Prabuty
Poland	Zofia Zamoyska nee Tarnowska Provincial Hospital in Tarnobrzeg	Tarnobrzeg
Poland	Ludwik Rydygier Provincial Hospital	Torun
Poland	MAGODENT Sp. z o .o. (LLC), Branch No. 4, Department of Clinical Oncology/Chemotherapy	Warsaw
Poland	Maria Sklodowska-Curie Institute of Oncology, Department of Lung and Thoracic Cancers	Warsaw
Serbia	Clinical Center of Serbia, Clinic of Pulmonology	Belgrade
Serbia	Clinical Hospital Center Bezanijska Kosa, Clinic of Oncology	Belgrade
Serbia	Institute of Oncology and Radiology of Serbia, Clinic of Medical Oncology	Belgrade
Serbia	Military Medical Academy	Belgrade
Serbia	Institute of Pulmonary Diseases of Vojvodina, Pulmonary Oncology Clinic	Sremska Kamenica
Serbia	Oncology Institute of Vojvodina	Sremska Kamenica
South Africa	GVI Outeniqua Oncology Unit	George
South Africa	Medical Oncology Centre of Rosebank	Johannesburg
Spain	Our Lady of Sonsoles Hospital	Avila
Spain	Hospital La Paz, Oncology Department	Madrid
Spain	Hospital Puerta de Hierro	Madrid
Spain	University Hospital Quiron Madrid, Department of Oncology	Madrid
Spain	Hospital Nuestra Senora de Valme	Sevilla	Andalucia
Ukraine	Chernivtsi Regional Clinical Oncology Center, Day Care Unit	Chernivtsi
Ukraine	Clinical Oncology Center, Department of Chemotherapy	Dnipropetrovsk
Ukraine	Dnipropetrovsk City Multispecialty Clinical Hospital #4, Department of Chemotherapy	Dnipropetrovsk
Ukraine	Regional Clinical Oncology Center, Chemotherapy Department	Ivano-Frankivsk
Ukraine	Kharkiv Regional Clinical Oncology Center, Chemotherapy Department #1	Kharkiv
Ukraine	S.P. Hryhoriev Institute of Medical Radiology, Department of Chemotherapy	Kharkiv
Ukraine	Khmelnytskyi Regional Oncology Center, Surgery Department #1	Khmelnytskyi
Ukraine	Kryvyi Rih Oncology Center, Department of Chemotherapy	Kryvyi Rih
Ukraine	Lviv State Regional Treatment and Diagnostics Oncology Center, Department of Chemotherapy	Lviv
Ukraine	Ternopil Regional Public Clinical Oncology Center	Ternopil
Ukraine	LTD UNIMED Adjara	Uzhhorod
Ukraine	Zakarpattia Regional Clinical Oncology Center, Department of Chemotherapy	Uzhhorod
Ukraine	Vinnytsia Regional Clinical Oncology Center, Department of Chemotherapy	Vinnytsia
Ukraine	Zaporizhia Regional Clinical Oncology Center, Thoracic Department	Zaporizhia
United States	Christus St. Frances Cabrini Hospital	Alexandria	Louisiana
United States	Indiana University Health Bloomington	Bloomington	Indiana
United States	Gabrail Cancer Center Research	Canton	Ohio
United States	North Shore Hematology Oncology Associates PC	East Setauket	New York
United States	West Cancer Center	Germantown	Tennessee
United States	St. Mary's Medical Center	Grand Junction	Colorado
United States	Provision Center for Biomedical Research	Knoxville	Tennessee
United States	Well Pharma Medical Research Corporation	Miami	Florida
United States	Illinois CancerCare	Peoria	Illinois
United States	Sarcoma Oncology Center	Santa Monica	California
United States	The Oncology Institute of Hope and Innovation	Whittier	California

Sponsors (2)

Lead Sponsor	Collaborator
Helsinn Healthcare SA	PSI CRO AG

Countries where clinical trial is conducted

United States,  Austria,  Croatia,  Czechia,  Germany,  Israel,  Italy,  Poland,  Serbia,  South Africa,  Spain,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Patients With Adverse Events	This is a safety study where Adverse Events is the primary outcome (defined by the current ICH Guideline for Good Clinical Practice). Patients are randomized according to a 1:1 ratio (IV NEPA FDC : oral NEPA FDC). No formal comparison is planned, the presence of a control in the same patient population helps interpret any unexpected safety finding in the experimental arm. It is expected that the number of patients randomized to the test group, i.e., 200, will allow approximately 100 patients to be treated with the test drug for 4 cycles. Based on 100 patients treated at Cycle 4 with the IV NEPA FDC , if a given Adverse Event (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 14 weeks assuming a maximum of 4 chemotherapy cycles given every 3 weeks.
Secondary	Percentage of Patients With Complete Response (CR) Defined as no Emesis, no Rescue Medication, in the Acute Phase		0-24 hours
Secondary	Percentage of Patients With Complete Response (CR) Defined as no Emesis, no Rescue Medication, in the Delayed Phase		>24-120 hours
Secondary	Percentage of Patients With Complete Response (CR) Defined as no Emesis, no Rescue Medication, in the Overall Phase		0-120 hours
Secondary	Percentage of Patients With no Emetic Episodes in the Acute Phase		0-24 hours
Secondary	Percentage of Patients With no Emetic Episodes in the Delayed Phase		>24-120 hours
Secondary	Percentage of Patients With no Emetic Episodes in the Overall Phase		0-120 hours
Secondary	Percentage of Patients With no Significant Nausea (VAS <25 mm) During the Acute Phase		0-24 hours
Secondary	Percentage of Patients With no Significant Nausea (VAS <25 mm) During the Delayed Phase		>24-120 hours
Secondary	Percentage of Patients With no Significant Nausea (VAS <25 mm) During the Overall Phase		0-120 hours