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

Phase 3

Completed

Conditions: Chemotherapy-Induced Nausea and Vomiting

Interventions: Drug: Pro-netupitant/Palonosetron
Drug: Netupitant/Palonosetron
Drug: Dexamethasone

Registration Number: NCT02517021

Lead Sponsor: Helsinn Healthcare SA

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 405

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pro-netupitant/Palonosetron plus Dexamethasone	Pro-netupitant/Palonosetron	Intravenous Pro-netupitant/Palonosetron (260 mg/0.25 mg) powder for solution for infusion (on Day 1) with oral dexamethasone prior to each scheduled chemotherapy cycle
Netupitant/Palonosetron plus Dexamethasone	Netupitant/Palonosetron	Oral netupitant/palonosetron (300 mg/0.50 mg) hard capsule (on Day 1) with oral dexamethasone prior to each scheduled chemotherapy cycle
Pro-netupitant/Palonosetron plus Dexamethasone	Dexamethasone	Intravenous Pro-netupitant/Palonosetron (260 mg/0.25 mg) powder for solution for infusion (on Day 1) with oral dexamethasone prior to each scheduled chemotherapy cycle
Netupitant/Palonosetron plus Dexamethasone	Dexamethasone	Oral netupitant/palonosetron (300 mg/0.50 mg) hard capsule (on Day 1) with oral dexamethasone prior to each scheduled chemotherapy cycle

Primary Outcome Measures

Name	Time	Method
Percentage of Patients With Adverse Events	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.	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.

Secondary Outcome Measures

Name	Time	Method
Percentage of Patients With no Emetic Episodes in the Acute Phase	0-24 hours
Percentage of Patients With no Emetic Episodes in the Delayed Phase	>24-120 hours
Percentage of Patients With no Emetic Episodes in the Overall Phase	0-120 hours
Percentage of Patients With no Significant Nausea (VAS <25 mm) During the Acute Phase	0-24 hours
Percentage of Patients With no Significant Nausea (VAS <25 mm) During the Delayed Phase	>24-120 hours
Percentage of Patients With no Significant Nausea (VAS <25 mm) During the Overall Phase	0-120 hours
Percentage of Patients With Complete Response (CR) Defined as no Emesis, no Rescue Medication, in the Acute Phase	0-24 hours
Percentage of Patients With Complete Response (CR) Defined as no Emesis, no Rescue Medication, in the Delayed Phase	>24-120 hours
Percentage of Patients With Complete Response (CR) Defined as no Emesis, no Rescue Medication, in the Overall Phase	0-120 hours

Trial Locations

Locations (74): Zakarpattia Regional Clinical Oncology Center, Department of Chemotherapy
🇺🇦
Uzhhorod, Ukraine
Well Pharma Medical Research Corporation
🇺🇸
Miami, Florida, United States
University Hospital Centre Zagreb "Jordanovac"
🇭🇷
Zagreb, Croatia
Masaryk's Hospital Usti nad Labem, Oncology Dept
🇨🇿
Usti nad Labem, Czechia
Provision Center for Biomedical Research
🇺🇸
Knoxville, Tennessee, United States
Krems Country Hospital
🇦🇹
Krems, Austria
Clinical Hospital Centre Osijek
🇭🇷
Osijek, Croatia
General Hospital Varazdin
🇭🇷
Varazdin, Croatia
Christus St. Frances Cabrini Hospital
🇺🇸
Alexandria, Louisiana, United States
North Shore Hematology Oncology Associates PC
🇺🇸
East Setauket, New York, United States
University Hospital Graz, Department of Internal Medicine
🇦🇹
Graz, Austria
University Hospital St. Poelten,1st Medical Department
🇦🇹
St. Poelten, Austria
Specialist Hospital in Prabuty Sp. z o .o. (LLC), Department of Pulmonology
🇵🇱
Prabuty, Poland
Clinical Hospital Center "Sestre milosrdnice"
🇭🇷
Zagreb, Croatia
Ternopil Regional Public Clinical Oncology Center
🇺🇦
Ternopil, Ukraine
Hospital La Paz, Oncology Department
🇪🇸
Madrid, Spain
Soroka University Medical Center,Oncology division
🇮🇱
Beer Sheva, Israel
The Oncology Institute of Hope and Innovation
🇺🇸
Whittier, California, United States
Illinois CancerCare
🇺🇸
Peoria, Illinois, United States
OncoResearch Lerchenfeld GmbH
🇩🇪
Hamburg, Germany
Regional Hospital "San Carlo"
🇮🇹
Potenza, Italy
Hospital Novy Jicin, Department of Oncology
🇨🇿
Novy Jicin, Czechia
Staedtisches Klinikum Muenchen GmbH; Klinikum N euperlach
🇩🇪
München, Germany
Ludwik Rydygier Provincial Hospital
🇵🇱
Torun, Poland
Chernivtsi Regional Clinical Oncology Center, Day Care Unit
🇺🇦
Chernivtsi, Ukraine
cientific Institute of Romagna for the Study and Treatment of Cancer (IRST), IRCCS
🇮🇹
Meldola, Italy
Dnipropetrovsk City Multispecialty Clinical Hospital #4, Department of Chemotherapy
🇺🇦
Dnipropetrovsk, Ukraine
Our Lady of Sonsoles Hospital
🇪🇸
Avila, Spain
Thomayer's Hospital, Clinic of Pneumology
🇨🇿
Prague, Czechia
Onkoligische Schwerpunktpraxis Bielefeld
🇩🇪
Bielefeld, Germany
Lord's Transfiguration Teaching Hospital, Department of Chemotherapy
🇵🇱
Poznan, Poland
Institute of Oncology and Radiology of Serbia, Clinic of Medical Oncology
🇷🇸
Belgrade, Serbia
Khmelnytskyi Regional Oncology Center, Surgery Department #1
🇺🇦
Khmelnytskyi, Ukraine
Hospital Puerta de Hierro
🇪🇸
Madrid, Spain
Hospital Na Bulovce
🇨🇿
Prague, Czechia
University Hospital Quiron Madrid, Department of Oncology
🇪🇸
Madrid, Spain
Regional Clinical Oncology Center, Chemotherapy Department
🇺🇦
Ivano-Frankivsk, Ukraine
Lviv State Regional Treatment and Diagnostics Oncology Center, Department of Chemotherapy
🇺🇦
Lviv, Ukraine
LTD UNIMED Adjara
🇺🇦
Uzhhorod, Ukraine
Vinnytsia Regional Clinical Oncology Center, Department of Chemotherapy
🇺🇦
Vinnytsia, Ukraine
S. G. Moscati Hospital, Medical Oncology Division
🇮🇹
Avellino, Italy
GVI Outeniqua Oncology Unit
🇿🇦
George, South Africa
National Cancer Institute, IRCCS, Medical Oncology Department
🇮🇹
Milan, Italy
Rambam Health Care Campus
🇮🇱
Haifa, Israel
Kryvyi Rih Oncology Center, Department of Chemotherapy
🇺🇦
Kryvyi Rih, Ukraine
Clinical Center of Serbia, Clinic of Pulmonology
🇷🇸
Belgrade, Serbia
Institute of Pulmonary Diseases of Vojvodina, Pulmonary Oncology Clinic
🇷🇸
Sremska Kamenica, Serbia
Provincial Hospitals in Gdynia Sp. z o.o. (LLC)
🇵🇱
Gdynia, Poland
Hospital Elisabethinen Linz GmbH, Internal Department #1 - Hemato-Oncology
🇦🇹
Linz, Austria
MAGODENT Sp. z o .o. (LLC), Branch No. 4, Department of Clinical Oncology/Chemotherapy
🇵🇱
Warsaw, Poland
Zofia Zamoyska nee Tarnowska Provincial Hospital in Tarnobrzeg
🇵🇱
Tarnobrzeg, Poland
Clinical Hospital Center Bezanijska Kosa, Clinic of Oncology
🇷🇸
Belgrade, Serbia
Oncology Institute of Vojvodina
🇷🇸
Sremska Kamenica, Serbia
Military Medical Academy
🇷🇸
Belgrade, Serbia
Sarcoma Oncology Center
🇺🇸
Santa Monica, California, United States
St. Mary's Medical Center
🇺🇸
Grand Junction, Colorado, United States
Indiana University Health Bloomington
🇺🇸
Bloomington, Indiana, United States
Gabrail Cancer Center Research
🇺🇸
Canton, Ohio, United States
Azienda Socio Sanitaria Territoriale-Monza (ASST-Monza) - Oncology Department
🇮🇹
Monza, Italy
West Cancer Center
🇺🇸
Germantown, Tennessee, United States
General Hospital Linz GmbH, Internal Medicine Department #3 - Center for Hematology and Medical Oncology
🇦🇹
Linz, Austria
University Hospital
🇨🇿
Brno, Czechia
University Hospital Brno. Clinic of Pulmonary Diseases and Tuberculosis
🇨🇿
Brno, Czechia
Hannover Medical School
🇩🇪
Hannover, Germany
Barziali Medical Center, Oncology Unit
🇮🇱
Ashkelon, Israel
Universitaetsklinikum Leipzig; Universitaeres Krebszentrum (UCCL)
🇩🇪
Leipzig, Germany
Local Healthcare Company of Vimercate (ASST Vimercate)
🇮🇹
Vimercate, Italy
Maria Sklodowska-Curie Institute of Oncology, Department of Lung and Thoracic Cancers
🇵🇱
Warsaw, Poland
Clinical Oncology Center, Department of Chemotherapy
🇺🇦
Dnipropetrovsk, Ukraine
Hospital Nuestra Senora de Valme
🇪🇸
Sevilla, Andalucia, Spain
Medical Oncology Centre of Rosebank
🇿🇦
Johannesburg, South Africa
Kharkiv Regional Clinical Oncology Center, Chemotherapy Department #1
🇺🇦
Kharkiv, Ukraine
S.P. Hryhoriev Institute of Medical Radiology, Department of Chemotherapy
🇺🇦
Kharkiv, Ukraine
Zaporizhia Regional Clinical Oncology Center, Thoracic Department
🇺🇦
Zaporizhia, Ukraine