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

NCT02517021 | Completed Phase 3 Results DMC

• 1 other identifier: NEPA-15-18
• Study Type: interventional
• Target: 405
• Locations: 12 countries
• Sites: 74

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.

Conditions

Chemotherapy-Induced Nausea and Vomiting

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• 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

• 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

Study Arms (2)

Pro-netupitant/Palonosetron plus Dexamethasone

EXPERIMENTAL

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

Drug: Pro-netupitant/Palonosetron; Drug: Dexamethasone

Netupitant/Palonosetron plus Dexamethasone

ACTIVE COMPARATOR

Oral netupitant/palonosetron (300 mg/0.50 mg) hard capsule (on Day 1) with oral dexamethasone prior to each scheduled chemotherapy cycle

Drug: Netupitant/Palonosetron; Drug: Dexamethasone

Interventions

Pro-netupitant/Palonosetron DRUG

Also known as: IV NEPA FDC

Pro-netupitant/Palonosetron plus Dexamethasone

Netupitant/Palonosetron DRUG

Also known as: Oral NEPA FDC

Netupitant/Palonosetron plus Dexamethasone

Dexamethasone DRUG

Netupitant/Palonosetron plus Dexamethasone; Pro-netupitant/Palonosetron plus Dexamethasone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Helsinn Healthcare SA: lead
• PSI CRO: collaborator

Study Sites (74)

Sarcoma Oncology Center

Santa Monica, California, 90403-480, United States

Location

The Oncology Institute of Hope and Innovation

Whittier, California, 90603, United States

Location

St. Mary's Medical Center

Grand Junction, Colorado, 81501, United States

Location

Well Pharma Medical Research Corporation

Miami, Florida, 33143, United States

Location

Illinois CancerCare

Peoria, Illinois, 61615-7822, United States

Location

Indiana University Health Bloomington

Bloomington, Indiana, 47403, United States

Location

Christus St. Frances Cabrini Hospital

Alexandria, Louisiana, 71301, United States

Location

North Shore Hematology Oncology Associates PC

East Setauket, New York, 11733, United States

Location

Gabrail Cancer Center Research

Canton, Ohio, 44718, United States

Location

West Cancer Center

Germantown, Tennessee, 38138, United States

Location

Provision Center for Biomedical Research

Knoxville, Tennessee, 37909, United States

Location

University Hospital Graz, Department of Internal Medicine

Graz, 8036, Austria

Location

Krems Country Hospital

Krems, Austria

Location

Hospital Elisabethinen Linz GmbH, Internal Department #1 - Hemato-Oncology

Linz, 4020, Austria

Location

General Hospital Linz GmbH, Internal Medicine Department #3 - Center for Hematology and Medical Oncology

Linz, 4021, Austria

Location

University Hospital St. Poelten,1st Medical Department

Sankt Pölten, Austria

Location

Clinical Hospital Centre Osijek

Osijek, Croatia

Location

General Hospital Varazdin

Varaždin, Croatia

Location

Clinical Hospital Center "Sestre milosrdnice"

Zagreb, Croatia

Location

University Hospital Centre Zagreb "Jordanovac"

Zagreb, Croatia

Location

University Hospital Brno. Clinic of Pulmonary Diseases and Tuberculosis

Brno, Czechia

Location

University Hospital

Brno, Czechia

Location

Hospital Novy Jicin, Department of Oncology

Nový Jičín, Czechia

Location

Thomayer's Hospital, Clinic of Pneumology

Prague, 140 59, Czechia

Location

Hospital Na Bulovce

Prague, Czechia

Location

Masaryk's Hospital Usti nad Labem, Oncology Dept

Ústí nad Labem, Czechia

Location

Onkoligische Schwerpunktpraxis Bielefeld

Bielefeld, Germany

Location

OncoResearch Lerchenfeld GmbH

Hamburg, Germany

Location

Hannover Medical School

Hanover, Germany

Location

Universitaetsklinikum Leipzig; Universitaeres Krebszentrum (UCCL)

Leipzig, Germany

Location

Staedtisches Klinikum Muenchen GmbH; Klinikum N euperlach

München, Germany

Location

Barziali Medical Center, Oncology Unit

Ashkelon, Israel

Location

Soroka University Medical Center,Oncology division

Beersheba, Israel

Location

Rambam Health Care Campus

Haifa, Israel

Location

S. G. Moscati Hospital, Medical Oncology Division

Avellino, Italy

Location

cientific Institute of Romagna for the Study and Treatment of Cancer (IRST), IRCCS

Meldola, Italy

Location

National Cancer Institute, IRCCS, Medical Oncology Department

Milan, Italy

Location

Azienda Socio Sanitaria Territoriale-Monza (ASST-Monza) - Oncology Department

Monza, Italy

Location

Regional Hospital "San Carlo"

Potenza, Italy

Location

Local Healthcare Company of Vimercate (ASST Vimercate)

Vimercate, Italy

Location

Provincial Hospitals in Gdynia Sp. z o.o. (LLC)

Gdynia, Poland

Location

Lord's Transfiguration Teaching Hospital, Department of Chemotherapy

Poznan, 60-569, Poland

Location

Specialist Hospital in Prabuty Sp. z o .o. (LLC), Department of Pulmonology

Prabuty, 82-550, Poland

Location

Zofia Zamoyska nee Tarnowska Provincial Hospital in Tarnobrzeg

Tarnobrzeg, Poland

Location

Ludwik Rydygier Provincial Hospital

Torun, Poland

Location

Maria Sklodowska-Curie Institute of Oncology, Department of Lung and Thoracic Cancers

Warsaw, 02-781, Poland

Location

MAGODENT Sp. z o .o. (LLC), Branch No. 4, Department of Clinical Oncology/Chemotherapy

Warsaw, 03-291, Poland

Location

Clinical Center of Serbia, Clinic of Pulmonology

Belgrade, Serbia

Location

Clinical Hospital Center Bezanijska Kosa, Clinic of Oncology

Belgrade, Serbia

Location

Institute of Oncology and Radiology of Serbia, Clinic of Medical Oncology

Belgrade, Serbia

Location

Military Medical Academy

Belgrade, Serbia

Location

Institute of Pulmonary Diseases of Vojvodina, Pulmonary Oncology Clinic

Kamenitz, Serbia

Location

Oncology Institute of Vojvodina

Kamenitz, Serbia

Location

GVI Outeniqua Oncology Unit

George, South Africa

Location

Medical Oncology Centre of Rosebank

Johannesburg, South Africa

Location

Hospital Nuestra Senora de Valme

Seville, Andalusia, Spain

Location

Our Lady of Sonsoles Hospital

Ávila, 05004, Spain

Location

Hospital Puerta de Hierro

Madrid, 28035, Spain

Location

Hospital La Paz, Oncology Department

Madrid, Spain

Location

University Hospital Quiron Madrid, Department of Oncology

Madrid, Spain

Location

Chernivtsi Regional Clinical Oncology Center, Day Care Unit

Chernivtsi, 58013, Ukraine

Location

Clinical Oncology Center, Department of Chemotherapy

Dnipropetrovsk, 49055, Ukraine

Location

Dnipropetrovsk City Multispecialty Clinical Hospital #4, Department of Chemotherapy

Dnipropetrovsk, 49102, Ukraine

Location

Regional Clinical Oncology Center, Chemotherapy Department

Ivano-Frankivsk, 76000, Ukraine

Location

S.P. Hryhoriev Institute of Medical Radiology, Department of Chemotherapy

Kharkiv, 61024, Ukraine

Location

Kharkiv Regional Clinical Oncology Center, Chemotherapy Department #1

Kharkiv, 61070, Ukraine

Location

Khmelnytskyi Regional Oncology Center, Surgery Department #1

Khmelnytskyi, 29009, Ukraine

Location

Kryvyi Rih Oncology Center, Department of Chemotherapy

Kryvyi Rih, 50048, Ukraine

Location

Lviv State Regional Treatment and Diagnostics Oncology Center, Department of Chemotherapy

Lviv, 79031, Ukraine

Location

Ternopil Regional Public Clinical Oncology Center

Ternopil, 46023, Ukraine

Location

LTD UNIMED Adjara

Uzhhorod, 88000, Ukraine

Location

Zakarpattia Regional Clinical Oncology Center, Department of Chemotherapy

Uzhhorod, 88014, Ukraine

Location

Vinnytsia Regional Clinical Oncology Center, Department of Chemotherapy

Vinnytsia, 21029, Ukraine

Location

Zaporizhia Regional Clinical Oncology Center, Thoracic Department

Zaporizhia, 69040, Ukraine

Location

Related Publications (1)

• 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.

  PMID: 29722791 DERIVED

MeSH Terms

Conditions

Vomiting

Interventions

Palonosetron; netupitant, palosentron drug combination; Dexamethasone

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quinuclidines; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Dr. Ruben Giorgino
• Organization: Helsinn Healthcare SA

ruben.giorgino@helsinn.com

+41 91 985 2121

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2015
• First Posted: August 6, 2015
• Study Start: November 1, 2015
• Primary Completion: August 1, 2016
• Study Completion: August 1, 2016
• Last Updated: June 20, 2018
• Results First Posted: June 20, 2018

Record last verified: 2018-06

Locations

US (11); PL (7); SE (6); AU (5); ES (5); DE (5); CZ (6); IT (6); IL (3); ZA (2); CR (4); UA (14)