A Study to Assess the Safety and the Efficacy of IV Fosnetupitant/Palonosetron (260 mg/0.25 mg) Combination Compared to Oral Netupitant/Palonosetron (300 mg/0.5 mg) Combination for the Prevention of CINV in AC Chemotherapy in Women With Breast Cancer

NCT ID: NCT03403712

Last Updated: 2020-06-01

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

404 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-03-16

Study Completion Date

2018-09-19

Brief Summary

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Multicenter, randomized, double-blind, double-dummy, parallel group, stratified study assessing the safety and describing the efficacy of a single dose of intravenous (IV) fosnetupitant/palonosetron (260 mg/0.25 mg) infusion \[test\] versus oral netupitant/palonosetron (300 mg/0.5 mg) combination \[control\]; each administered with oral dexamethasone prior to initial and repeated cycles of AC chemotherapy in female breast cancer patients.

Detailed Description

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Conditions

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Chemotherapy-induced Nausea and Vomiting

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Test group

intravenous fosnetupitant/ palonosetron (260 mg/0.25 mg) fixed-dose combination, administered as a 30-minute infusion of a 50 mL solution, on Day 1 of each cycle.

Oral dexamethasone will be administered on Day 1 of each cycle (12 mg)

Group Type EXPERIMENTAL

fosnetupitant/ palonosetron

Intervention Type DRUG

intravenous fosnetupitant/ palonosetron (260 mg/0.25 mg) fixed-dose combination

dexamethasone

Intervention Type DRUG

Oral dexamethasone (12 mg)

Control group

oral netupitant/palonosetron (300 mg/0.50 mg) fixed-dose combination on Day 1 of each cycle.

Oral dexamethasone will be administered on Day 1 of each cycle (12 mg)

Group Type ACTIVE_COMPARATOR

netupitant/palonosetron

Intervention Type DRUG

oral netupitant/palonosetron (300 mg/0.50 mg) fixed-dose combination

dexamethasone

Intervention Type DRUG

Oral dexamethasone (12 mg)

Interventions

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fosnetupitant/ palonosetron

intravenous fosnetupitant/ palonosetron (260 mg/0.25 mg) fixed-dose combination

Intervention Type DRUG

netupitant/palonosetron

oral netupitant/palonosetron (300 mg/0.50 mg) fixed-dose combination

Intervention Type DRUG

dexamethasone

Oral dexamethasone (12 mg)

Intervention Type DRUG

Other Intervention Names

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IV NEPA FDC Akynzeo capsules

Eligibility Criteria

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Inclusion Criteria

Cycle 1:


1. Patient read, understood and signed the written informed consent before any study related activity, agreeing to participate in the study and to comply with study requirements.
2. Female patient of at least 8 years of age.
3. Histologically or cytologically confirmed breast cancer, including recurrent or metastatic.
4. Naïve to moderately or highly emetogenic antineoplastic agents.
5. Scheduled to receive at least 4 consecutive cycles of an AC combination regimen.

Notes:
1. additional not emetogenic, minimally or low emetogenic antineoplastic agents are permitted at any time after start of AC combination on Day 1.
2. additional highly or moderately emetogenic antineoplastic agents are only allowed on Day 1 after the start of AC combination, provided their administration is completed within 6 hours from the start of the AC combination administration.
6. ECOG Performance Status of 0 or 1.
7. Patient shall be: a) of non-childbearing potential or b) of childbearing potential using reliable contraceptive measures and having a negative urine pregnancy test within 24 hours prior to dose of investigational product.

Notes:
1. Female patients of non-childberaring potential are defined as being in post-menopausal state since at least 1 year; or having documented surgical sterilization or hysterectomy at least 3 months before study participation.
2. Reliable contraceptive measures include implants, injectables, combined oral contraceptives, intrauterine devices, vasectomized partner or complete (long term) sexual abstinence;
8. Hematologic and metabolic status adequate for receiving a cycle of AC chemotherapy based on investigator's assessment.
9. If the patient has a known hepatic or renal impairment, she may be enrolled in the study at the discretion of the Investigator.
10. Able to read, understand, follow the study procedure and complete the patient diary.


Cycles 2 to 4:


1. 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.
2. Scheduled to receive an AC chemotherapy regimen or AC chemotherapy together with other chemotherapies as defined in Inclusion criterion #5 for Cycle 1.
3. Patient shall be: a) of non-childbearing potential or b) of childbearing potential using reliable contraceptive measures and having a negative urine pregnancy test within 24 hours prior to dosing of investigational product.
4. Adequate hematologic and metabolic status for receiving a cycle of AC chemotherapy according to the Investigator's opinion.

Exclusion Criteria

Cycle 1:


1. Lactating patient.
2. Current use of illicit drugs or current evidence of alcohol abuse.
3. Scheduled to receive moderately or highly emetogenic antineoplastic agent in addition to the AC regimen, from 6 hours after the start of the AC chemotherapy on Day 1 and up to Day 1 of Cycle 2.
4. Received or is scheduled to receive radiation therapy to the abdomen or the pelvis within 1 week prior to the start of AC chemotherapy administration on Day 1 or between Days 1 to 5, inclusive.
5. Any vomiting, retching, or nausea (grade 1 as defined by National Cancer Institute) within 24 hours prior to the start of AC chemotherapy administration on Day 1.
6. Symptomatic primary or metastatic central nervous system (CNS) malignancy.
7. Active peptic ulcer disease, gastrointestinal obstruction, increased intracranial pressure, hypercalcemia, an active infection or any illness or medical conditions (other than malignancy) that, in the opinion of the Investigator, may confound the results of the study, represent another potential etiology for emesis and nausea (other than chemotherapy-induced nausea and vomiting \[CINV\]) or pose unwarranted risks in administering the study drugs to the patient.
8. Known hypersensitivity or contraindication to 5 hydroxytryptamine type 3 (5-HT3) receptor antagonists (e.g., palonosetron, ondansetron, granisetron, dolasetron, tropisetron, ramosetron), to dexamethasone, or to neurokinin-1 (NK1) receptor antagonists (e.g., aprepitant, rolapitant).
9. Known contraindication to the IV administration of 50 mL 5% glucose solution.
10. Participation in a previous clinical trial involving IV fosnetupitant or oral netupitant administered alone or in combination with palonosetron.
11. Any investigational drugs taken within 4 weeks prior to Day 1, and/or is scheduled to receive any investigational drug (other than those planned by the study protocol) during the present study.
12. Systemic corticosteroid therapy within 72 hours prior to the start of AC chemotherapy administration on Day 1, except the dexamethasone provided as additional study drug. However, topical and inhaled corticosteroids are permitted.
13. Scheduled to receive bone marrow transplantation and/or stem cell rescue therapy during the study participation.
14. Other than as administered as part of the study protocol, any medication with known or potential antiemetic activity within 24 hours prior to the start of AC chemotherapy administration on Day 1, including:

* 5-HT3 receptor antagonists (e.g., ondansetron, granisetron, dolasetron, tropisetron, ramosetron, palonosetron)
* NK1 receptor antagonists (e.g., aprepitant, fosaprepitant, rolapitant or any other new drug of this class)
* benzamides (e.g., metoclopramide, alizapride)
* phenothiazines (e.g., prochlorperazine, promethazine, fluphenazine, perphenazine, thiethylperazine, chlorpromazine)
* benzodiazepines (except if the subject is receiving such medication for sleep or anxiety and has been on a stable dose for at least seven days prior to Day 1).
* butyrophenones (e.g., haloperidol, droperidol)
* anticholinergics (e.g., scopolamine, with the exception of inhaled anticholinergics for respiratory disorders, e.g., ipratropium bromide)
* antihistamines (e.g., cyclizine, hydroxyzine, diphenhydramine, chlorpheniramine)
* domperidone
* mirtazapine
* olanzapine
* prescribed cannabinoids (e.g., tetrahydrocannabinol or nabilone)
* Over The Counter (OTC) antiemetics, OTC cold or OTC allergy medications.
15. Scheduled to receive any strong or moderate inhibitor of CYP3A4 during the efficacy assessment period (Day 1 to Day 5, inclusive) or its intake within 1 week prior to Day 1.
16. Scheduled to receive any CYP3A4 inducer during the efficacy assessment period (Day 1 to Day 5, inclusive) or its intake within 4 weeks prior to Day 1, with the exception of corticosteroids (for which exclusion criterion #12 applies).
17. History or predisposition to cardiac conduction abnormalities, except for incomplete right bundle branch block.
18. History of risk factors for Torsades de Pointes (heart failure, hypokalemia, family history of Long QT Syndrome).
19. Severe or uncontrolled cardiovascular diseases, including myocardial infarction within 3 months prior to Day 1, 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.



Cycles 2 to 4:


1. Scheduled to receive moderately or highly emetogenic antineoplastic agent in addition to the AC regimen, from 6 hours after the start of the AC chemotherapy on Day 1 of current cycle and up to Day 1 of the next cycle.
2. Active infection or uncontrolled disease that may pose unwarranted risks in administering the study drugs to the patient.
3. Started any of the prohibited medications.
4. Any vomiting, retching, or nausea (grade ≥ 1 as defined by National Cancer Institute) within 24 hours prior to the start of AC chemotherapy administration on Day 1.
5. Received or is scheduled to receive radiation therapy to the abdomen or the pelvis within 1 week prior to the start of AC chemotherapy administration on Day 1 or between Days 1 to 5.
6. Symptomatic primary or metastatic CNS malignancy.
7. Any illness or medical condition that, in the opinion of the investigator, may confound the results of the study or pose unwarranted risks in administering the investigational product or dexamethasone to the patient.
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Emerald Clinical Inc.

INDUSTRY

Sponsor Role collaborator

The Physicians' Services Incorporated Foundation

OTHER

Sponsor Role collaborator

Helsinn Healthcare SA

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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The Oncology Inst. Of Hope and Innovation

Tucson, Arizona, United States

Site Status

Carti Cancer Center

Little Rock, Arkansas, United States

Site Status

Pacific Cancer Medical Center, Inc.

Anaheim, California, United States

Site Status

CBCC Global Research, INC at Comprehensive Blood and Cancer Center

Bakersfield, California, United States

Site Status

The Oncology Tnstitute of Hope and Innovation

Corona, California, United States

Site Status

Uptimum Medical Group Inc.

Inglewood, California, United States

Site Status

The Oncology Institute of Hope and Innnovation

Long Beach, California, United States

Site Status

Hao Wei Zhang M.D.

Los Angeles, California, United States

Site Status

Emad Ibrahim, MD, INC.

Redlands, California, United States

Site Status

Watson Clinic LLP

Lakeland, Florida, United States

Site Status

Mid Florida Hematology and Oncology Center

Orange City, Florida, United States

Site Status

University Cancer & Blood Center, LLC

Athens, Georgia, United States

Site Status

Cancer Center of !\!Iiddle Georgia

Dublin, Georgia, United States

Site Status

Harbin Clinic

Rome, Georgia, United States

Site Status

Summit Cancer Care

Savannah, Georgia, United States

Site Status

Edward H. Kaplan MD & Associates

Skokie, Illinois, United States

Site Status

Presence Infusion Care - Skokie

Skokie, Illinois, United States

Site Status

Fort Wayne Medical Oncology and Hematology, Inc.

Fort Wayne, Indiana, United States

Site Status

TU Health Arnett Cancer Center

Lafayette, Indiana, United States

Site Status

Baptist Health Cancer Center

New Albany, Indiana, United States

Site Status

Cotton O'Neil Clinical Res. Ctr., Hematology & Oncology

Topeka, Kansas, United States

Site Status

Cancer Center of Kansas

Wichita, Kansas, United States

Site Status

Ashland-Bellefonte Cancer Center

Ashland, Kentucky, United States

Site Status

CHRISTUS Cancer Treatment Center

Shreveport, Louisiana, United States

Site Status

Mercy Medical Center, Medical Oncology and Hematology

Baltimore, Maryland, United States

Site Status

Hattiesburg Clinic Hematology Oncology

Hattiesburg, Mississippi, United States

Site Status

Cornell-Beshore Cancer Institute

Joplin, Missouri, United States

Site Status

Cox Mcdical ·Centers

Springfield, Missouri, United States

Site Status

Trinitas Cancer Center

Elizabeth, New Jersey, United States

Site Status

San Juan Oncology Associates

Farmington, New Mexico, United States

Site Status

Mid Ohio Oncology/Hematology Inc. DBA The Mark H. Zangmeister Center

Columbus, Ohio, United States

Site Status

Toledo Clinic Cancer Center - Toledo

Toledo, Ohio, United States

Site Status

Monongahela Valley Hospital

Monongahela, Pennsylvania, United States

Site Status

Carolina Blood and Cancer Care Associates, P.A.

Rock Hill, South Carolina, United States

Site Status

The West Clinic, PC dba West Cancer Center

Germantown, Tennessee, United States

Site Status

Cheyenne Regional Medical Center

Cheyenne, Wyoming, United States

Site Status

JSC Saint Nikolozi Surgery and Oncological Centre

Kutaisi, , Georgia

Site Status

LTD Institute of Clinical Oncology

Tbilisi, , Georgia

Site Status

LTD Tbilisi Oncology Dispensary

Tbilisi, , Georgia

Site Status

LTD S.Khechinashvili University Hospital

Tbilisi, , Georgia

Site Status

Countries

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United States Georgia

References

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Navari R, Binder G, Molasiotis A, Herrstedt J, Roeland EJ, Ruddy KJ, LeBlanc TW, Kloth DD, Klute KA, Papademetriou E, Schmerold L, Schwartzberg L. Duration of Chemotherapy-Induced Nausea and Vomiting (CINV) as a Predictor of Recurrent CINV in Later Cycles. Oncologist. 2023 Mar 17;28(3):208-213. doi: 10.1093/oncolo/oyac240.

Reference Type DERIVED
PMID: 36527702 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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NEPA-17-05

Identifier Type: -

Identifier Source: org_study_id

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