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

NCT03403712 | Completed Phase 3 Results FDA Drug

• 1 other identifier: NEPA-17-05
• Study Type: interventional
• Target: 404
• Locations: 2 countries
• Sites: 40

Brief Summary

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.

Conditions

Chemotherapy-induced Nausea and Vomiting

Outcome Measures

Primary Outcomes (4)

• Number of Participants With Treatment-emergent AEs at Cycle 1

  At the end of Cycle 1 (each cycle is 21 days)

• Number of Participants With Treatment-emergent AEs All Cycles

  At the end of Cycle 4 (each cycle is 21 days)

• Number of Participants With Severe (i.e., CTCAE Grade ≥3) TEAEs Reported for ≥2% of Patients in Either Treatment Group and Overall Throughout the Study

  At the end of Cycle 4 (each cycle is 21 days)

• Number of Participants With Study-Drug-Related TEAEs Reported for ≥2% of Patients in Either Treatment Group Throughout the Study

  At the end of Cycle 4 (each cycle is 21 days)

Secondary Outcomes (4)

• Complete Response in Cycle 1 During the Acute Phase

  24 hours after the start of AC chemotherapy administration

• Complete Response in Cycle 1 During the Delayed Phase

  120 hour after the start of AC chemotherapy administration

• Complete Response in Cycle 1 During the Overall Phase

  0-120 hours after the start of AC chemotherapy

• Overall Percentage of Patients With NIDL Based on FLIE Scores for Cycles 1

  cycle 1

Study Arms (2)

Test group

EXPERIMENTAL

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)

Drug: fosnetupitant/ palonosetron; Drug: dexamethasone

Control group

ACTIVE COMPARATOR

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)

Drug: netupitant/palonosetron; Drug: dexamethasone

Interventions

fosnetupitant/ palonosetron DRUG

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

Also known as: IV NEPA FDC

Test group

netupitant/palonosetron DRUG

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

Also known as: Akynzeo capsules

Control group

dexamethasone DRUG

Oral dexamethasone (12 mg)

Control group; Test group

Eligibility Criteria

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

You may qualify if:

• Cycle 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.
• Female patient of at least 8 years of age.
• Histologically or cytologically confirmed breast cancer, including recurrent or metastatic.
• Naïve to moderately or highly emetogenic antineoplastic agents.
• Scheduled to receive at least 4 consecutive cycles of an AC combination regimen.
• Notes:
• additional not emetogenic, minimally or low emetogenic antineoplastic agents are permitted at any time after start of AC combination on Day 1.
• 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.
• ECOG Performance Status of 0 or 1.
• 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:
• 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.
• Reliable contraceptive measures include implants, injectables, combined oral contraceptives, intrauterine devices, vasectomized partner or complete (long term) sexual abstinence;
• Hematologic and metabolic status adequate for receiving a cycle of AC chemotherapy based on investigator's assessment.

You may not qualify if:

• Cycle 1:
• Lactating patient.
• Current use of illicit drugs or current evidence of alcohol abuse.
• 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.
• 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.
• 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.
• Symptomatic primary or metastatic central nervous system (CNS) malignancy.
• 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.
• 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).
• Known contraindication to the IV administration of 50 mL 5% glucose solution.
• Participation in a previous clinical trial involving IV fosnetupitant or oral netupitant administered alone or in combination with palonosetron.
• 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.
• 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.
• Scheduled to receive bone marrow transplantation and/or stem cell rescue therapy during the study participation.
• 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:

Sponsors & Collaborators

• Helsinn Healthcare SA: lead
• Emerald Clinical Inc.: collaborator
• The Physicians' Services Incorporated Foundation: collaborator

Study Sites (40)

The Oncology Inst. Of Hope and Innovation

Tucson, Arizona, 85745, United States

Location

Carti Cancer Center

Little Rock, Arkansas, 72205, United States

Location

Pacific Cancer Medical Center, Inc.

Anaheim, California, 92801, United States

Location

CBCC Global Research, INC at Comprehensive Blood and Cancer Center

Bakersfield, California, 93309, United States

Location

The Oncology Tnstitute of Hope and Innovation

Corona, California, 92882, United States

Location

Uptimum Medical Group Inc.

Inglewood, California, 90305, United States

Location

The Oncology Institute of Hope and Innnovation

Long Beach, California, 90805, United States

Location

Hao Wei Zhang M.D.

Los Angeles, California, 90033, United States

Location

Emad Ibrahim, MD, INC.

Redlands, California, 92373, United States

Location

Watson Clinic LLP

Lakeland, Florida, 33805, United States

Location

Mid Florida Hematology and Oncology Center

Orange City, Florida, 32763, United States

Location

University Cancer & Blood Center, LLC

Athens, Georgia, 30607, United States

Location

Cancer Center of !\!Iiddle Georgia

Dublin, Georgia, 31021, United States

Location

Harbin Clinic

Rome, Georgia, 30165, United States

Location

Summit Cancer Care

Savannah, Georgia, 31404, United States

Location

Edward H. Kaplan MD & Associates

Skokie, Illinois, 60076, United States

Location

Presence Infusion Care - Skokie

Skokie, Illinois, 60077, United States

Location

Fort Wayne Medical Oncology and Hematology, Inc.

Fort Wayne, Indiana, 46845, United States

Location

TU Health Arnett Cancer Center

Lafayette, Indiana, 47904, United States

Location

Baptist Health Cancer Center

New Albany, Indiana, 47150, United States

Location

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

Topeka, Kansas, 66606, United States

Location

Cancer Center of Kansas

Wichita, Kansas, 67214, United States

Location

Ashland-Bellefonte Cancer Center

Ashland, Kentucky, 41101, United States

Location

CHRISTUS Cancer Treatment Center

Shreveport, Louisiana, 71105, United States

Location

Mercy Medical Center, Medical Oncology and Hematology

Baltimore, Maryland, 21202, United States

Location

Hattiesburg Clinic Hematology Oncology

Hattiesburg, Mississippi, 39401, United States

Location

Cornell-Beshore Cancer Institute

Joplin, Missouri, 64804, United States

Location

Cox Mcdical ·Centers

Springfield, Missouri, 65807, United States

Location

Trinitas Cancer Center

Elizabeth, New Jersey, 07207, United States

Location

San Juan Oncology Associates

Farmington, New Mexico, 87401, United States

Location

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

Columbus, Ohio, 43219, United States

Location

Toledo Clinic Cancer Center - Toledo

Toledo, Ohio, 43623, United States

Location

Monongahela Valley Hospital

Monongahela, Pennsylvania, 15063, United States

Location

Carolina Blood and Cancer Care Associates, P.A.

Rock Hill, South Carolina, 29732, United States

Location

The West Clinic, PC dba West Cancer Center

Germantown, Tennessee, 38138, United States

Location

Cheyenne Regional Medical Center

Cheyenne, Wyoming, 82001, United States

Location

JSC Saint Nikolozi Surgery and Oncological Centre

Kutaisi, 4600, Georgia

Location

LTD Institute of Clinical Oncology

Tbilisi, 0159, Georgia

Location

LTD Tbilisi Oncology Dispensary

Tbilisi, 0159, Georgia

Location

LTD S.Khechinashvili University Hospital

Tbilisi, 0179, Georgia

Location

Related Publications (1)

• 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.

  PMID: 36527702 DERIVED

MeSH Terms

Conditions

Vomiting

Interventions

netupitant, palosentron drug combination; Dexamethasone

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Head of Clinical Development
• Organization: Helsinn SA

info-HHC@helsinn.com

+41 91 985 2121

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: January 4, 2018
• First Posted: January 19, 2018
• Study Start: March 16, 2018
• Primary Completion: September 19, 2018
• Study Completion: September 19, 2018
• Last Updated: June 1, 2020
• Results First Posted: April 15, 2020

Record last verified: 2020-05

Locations

US (36); GE (4)