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

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

Sponsors

Lead Sponsor: Helsinn Healthcare SA

Collaborator: PSI CRO AG

Source 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.

Overall Status Completed
Start Date November 2015
Completion Date August 2016
Primary Completion Date August 2016
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
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.
Secondary Outcome
Measure Time Frame
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
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
Enrollment 405
Condition
Intervention

Intervention Type: Drug

Intervention Name: Pro-netupitant/Palonosetron

Arm Group Label: Pro-netupitant/Palonosetron plus Dexamethasone

Other Name: IV NEPA FDC

Intervention Type: Drug

Intervention Name: Netupitant/Palonosetron

Arm Group Label: Netupitant/Palonosetron plus Dexamethasone

Other Name: Oral NEPA FDC

Intervention Type: Drug

Intervention Name: Dexamethasone

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.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Location
Facility:
Sarcoma Oncology Center | Santa Monica, California, 90403-480, United States
The Oncology Institute of Hope and Innovation | Whittier, California, 90603, United States
St. Mary's Medical Center | Grand Junction, Colorado, 81501, United States
Well Pharma Medical Research Corporation | Miami, Florida, 33143, United States
Illinois CancerCare | Peoria, Illinois, 61615-7822, United States
Indiana University Health Bloomington | Bloomington, Indiana, 47403, United States
Christus St. Frances Cabrini Hospital | Alexandria, Louisiana, 71301, United States
North Shore Hematology Oncology Associates PC | East Setauket, New York, 11733, United States
Gabrail Cancer Center Research | Canton, Ohio, 44718, United States
West Cancer Center | Germantown, Tennessee, 38138, United States
Provision Center for Biomedical Research | Knoxville, Tennessee, 37909, United States
University Hospital Graz, Department of Internal Medicine | Graz, 8036, Austria
Krems Country Hospital | Krems, Austria
Hospital Elisabethinen Linz GmbH, Internal Department #1 - Hemato-Oncology | Linz, 4020, Austria
General Hospital Linz GmbH, Internal Medicine Department #3 - Center for Hematology and Medical Oncology | Linz, 4021, Austria
University Hospital St. Poelten,1st Medical Department | St. Poelten, Austria
Clinical Hospital Centre Osijek | Osijek, Croatia
General Hospital Varazdin | Varazdin, Croatia
Clinical Hospital Center "Sestre milosrdnice" | Zagreb, Croatia
University Hospital Centre Zagreb "Jordanovac" | Zagreb, Croatia
University Hospital Brno. Clinic of Pulmonary Diseases and Tuberculosis | Brno, Czechia
University Hospital | Brno, Czechia
Hospital Novy Jicin, Department of Oncology | Novy Jicin, Czechia
Thomayer's Hospital, Clinic of Pneumology | Prague, 140 59, Czechia
Hospital Na Bulovce | Prague, Czechia
Masaryk's Hospital Usti nad Labem, Oncology Dept | Usti nad Labem, Czechia
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, Germany
Barziali Medical Center, Oncology Unit | Ashkelon, Israel
Soroka University Medical Center,Oncology division | Beer Sheva, Israel
Rambam Health Care Campus | Haifa, Israel
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, Italy
Provincial Hospitals in Gdynia Sp. z o.o. (LLC) | Gdynia, Poland
Lord's Transfiguration Teaching Hospital, Department of Chemotherapy | Poznan, 60-569, Poland
Specialist Hospital in Prabuty Sp. z o .o. (LLC), Department of Pulmonology | Prabuty, 82-550, Poland
Zofia Zamoyska nee Tarnowska Provincial Hospital in Tarnobrzeg | Tarnobrzeg, Poland
Ludwik Rydygier Provincial Hospital | Torun, Poland
Maria Sklodowska-Curie Institute of Oncology, Department of Lung and Thoracic Cancers | Warsaw, 02-781, Poland
MAGODENT Sp. z o .o. (LLC), Branch No. 4, Department of Clinical Oncology/Chemotherapy | Warsaw, 03-291, Poland
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, Serbia
GVI Outeniqua Oncology Unit | George, South Africa
Medical Oncology Centre of Rosebank | Johannesburg, South Africa
Hospital Nuestra Senora de Valme | Sevilla, Andalucia, Spain
Our Lady of Sonsoles Hospital | Avila, 05004, Spain
Hospital Puerta de Hierro | Madrid, 28035, Spain
Hospital La Paz, Oncology Department | Madrid, Spain
University Hospital Quiron Madrid, Department of Oncology | Madrid, Spain
Chernivtsi Regional Clinical Oncology Center, Day Care Unit | Chernivtsi, 58013, Ukraine
Clinical Oncology Center, Department of Chemotherapy | Dnipropetrovsk, 49055, Ukraine
Dnipropetrovsk City Multispecialty Clinical Hospital #4, Department of Chemotherapy | Dnipropetrovsk, 49102, Ukraine
Regional Clinical Oncology Center, Chemotherapy Department | Ivano-Frankivsk, 76000, Ukraine
S.P. Hryhoriev Institute of Medical Radiology, Department of Chemotherapy | Kharkiv, 61024, Ukraine
Kharkiv Regional Clinical Oncology Center, Chemotherapy Department #1 | Kharkiv, 61070, Ukraine
Khmelnytskyi Regional Oncology Center, Surgery Department #1 | Khmelnytskyi, 29009, Ukraine
Kryvyi Rih Oncology Center, Department of Chemotherapy | Kryvyi Rih, 50048, Ukraine
Lviv State Regional Treatment and Diagnostics Oncology Center, Department of Chemotherapy | Lviv, 79031, Ukraine
Ternopil Regional Public Clinical Oncology Center | Ternopil, 46023, Ukraine
LTD UNIMED Adjara | Uzhhorod, 88000, Ukraine
Zakarpattia Regional Clinical Oncology Center, Department of Chemotherapy | Uzhhorod, 88014, Ukraine
Vinnytsia Regional Clinical Oncology Center, Department of Chemotherapy | Vinnytsia, 21029, Ukraine
Zaporizhia Regional Clinical Oncology Center, Thoracic Department | Zaporizhia, 69040, Ukraine
Location Countries

Austria

Croatia

Czechia

Germany

Israel

Italy

Poland

Serbia

South Africa

Spain

Ukraine

United States

Verification Date

June 2018

Responsible Party

Type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Pro-netupitant/Palonosetron plus Dexamethasone

Type: Experimental

Description: 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

Label: Netupitant/Palonosetron plus Dexamethasone

Type: Active Comparator

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

Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Prevention

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Source: ClinicalTrials.gov