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Chemotherapy-induced Nausea and VomitingPhase 3NCT03403712

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

A Phase 3 study testing fosnetupitant/ palonosetron, netupitant/palonosetron and dexamethasone in people with Chemotherapy-induced Nausea and Vomiting, run by Helsinn Healthcare SA at 40 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Chemotherapy-induced Nausea and Vomiting
What is being tested?
fosnetupitant/ palonosetron, netupitant/palonosetron and dexamethasone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
404 participants
Where
40 sitesin 2 countries
Study dates
16 Mar 2018to 19 Sep 2018
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Cycle 1:
  • The following inclusion criteria must be checked prior to inclusion at 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.
Show all 26Show fewer
  • 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.
  • If the patient has a known hepatic or renal impairment, she may be enrolled in the study at the discretion of the Investigator.
  • Able to read, understand, follow the study procedure and complete the patient diary.
  • All inclusion criteria will be checked at screening visit (Visit 1 of Cycle 1); inclusion criteria 7 will be re-checked at Day 1 (Visit 2).
  • 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 an AC chemotherapy regimen or AC chemotherapy together with other chemotherapies as defined in Inclusion criterion #5 for Cycle 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 dosing of investigational product.
  • Adequate hematologic and metabolic status for receiving a cycle of AC chemotherapy according to the Investigator's opinion.
  • All inclusion criteria will be checked at screening visit (Visit 1); inclusion criterion #3 will be re-checked at Day 1 (Visit 2).

Who cannot join

  • Cycle 1:
  • The following exclusion criteria must be checked prior to inclusion at 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.
Show all 46Show fewer
  • 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:
  • 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.
  • 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.
  • 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).
  • History or predisposition to cardiac conduction abnormalities, except for incomplete right bundle branch block.
  • History of risk factors for Torsades de Pointes (heart failure, hypokalemia, family history of Long QT Syndrome).
  • 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.
  • All exclusion criteria with the exception of criteria #5, #12, and #14 will be checked at screening visit (Visit 1). Exclusion criteria #5, #12, and #14 will be checked at Day 1 (Visit 2) only.
  • Exclusion criteria #3, #4, #7, #11, #13, #15, and #16 need to be re-checked at Day 1 (Visit 2).
  • Cycles 2 to 4:
  • The following exclusion criteria must be checked prior to inclusion at each repeated cycle:
  • 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.
  • Active infection or uncontrolled disease that may pose unwarranted risks in administering the study drugs to the patient.
  • Started any of the prohibited medications.
  • 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.
  • 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.
  • Symptomatic primary or metastatic CNS malignancy.
  • 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.
  • All exclusion criteria, with exception of criterion #4, will be checked at screening visit (Visit 1). Exclusion criterion #4 will be checked at Day 1 (Visit 2) only. Exclusion criteria #2, #3 and #5 need to be re-checked at Day 1 (Visit 2).

Trial locations and contacts

40 sites in 2 countries.

40 sites in 2 countries

United States36 sites

  • Pacific Cancer Medical Center, Inc.

    Anaheim, California, 92801

  • Ashland-Bellefonte Cancer Center

    Ashland, Kentucky, 41101

  • University Cancer & Blood Center, LLC

    Athens, Georgia, 30607

  • CBCC Global Research, INC at Comprehensive Blood and Cancer Center

    Bakersfield, California, 93309

  • Mercy Medical Center, Medical Oncology and Hematology

    Baltimore, Maryland, 21202

  • Cheyenne Regional Medical Center

    Cheyenne, Wyoming, 82001

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

    Columbus, Ohio, 43219

  • The Oncology Tnstitute of Hope and Innovation

    Corona, California, 92882

  • Cancer Center of !\!Iiddle Georgia

    Dublin, Georgia, 31021

  • Trinitas Cancer Center

    Elizabeth, New Jersey, 07207

  • San Juan Oncology Associates

    Farmington, New Mexico, 87401

  • Fort Wayne Medical Oncology and Hematology, Inc.

    Fort Wayne, Indiana, 46845

  • The West Clinic, PC dba West Cancer Center

    Germantown, Tennessee, 38138

  • Hattiesburg Clinic Hematology Oncology

    Hattiesburg, Mississippi, 39401

  • Uptimum Medical Group Inc.

    Inglewood, California, 90305

  • Cornell-Beshore Cancer Institute

    Joplin, Missouri, 64804

  • TU Health Arnett Cancer Center

    Lafayette, Indiana, 47904

  • Watson Clinic LLP

    Lakeland, Florida, 33805

  • Carti Cancer Center

    Little Rock, Arkansas, 72205

  • The Oncology Institute of Hope and Innnovation

    Long Beach, California, 90805

  • Hao Wei Zhang M.D.

    Los Angeles, California, 90033

  • Monongahela Valley Hospital

    Monongahela, Pennsylvania, 15063

  • Baptist Health Cancer Center

    New Albany, Indiana, 47150

  • Mid Florida Hematology and Oncology Center

    Orange City, Florida, 32763

  • Emad Ibrahim, MD, INC.

    Redlands, California, 92373

  • Carolina Blood and Cancer Care Associates, P.A.

    Rock Hill, South Carolina, 29732

  • Harbin Clinic

    Rome, Georgia, 30165

  • Summit Cancer Care

    Savannah, Georgia, 31404

  • CHRISTUS Cancer Treatment Center

    Shreveport, Louisiana, 71105

  • Edward H. Kaplan MD & Associates

    Skokie, Illinois, 60076

  • Presence Infusion Care - Skokie

    Skokie, Illinois, 60077

  • Cox Mcdical ·Centers

    Springfield, Missouri, 65807

  • Toledo Clinic Cancer Center - Toledo

    Toledo, Ohio, 43623

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

    Topeka, Kansas, 66606

  • The Oncology Inst. Of Hope and Innovation

    Tucson, Arizona, 85745

  • Cancer Center of Kansas

    Wichita, Kansas, 67214

Other trials in United States

Georgia4 sites

  • JSC Saint Nikolozi Surgery and Oncological Centre

    Kutaisi, 4600

  • LTD Institute of Clinical Oncology

    Tbilisi, 0159

  • LTD Tbilisi Oncology Dispensary

    Tbilisi, 0159

  • LTD S.Khechinashvili University Hospital

    Tbilisi, 0179

Other trials in Georgia

About this study

Official title: A Multicenter, Randomized, Double-blind, Double-dummy, Active-controlled, Parallel Group Phase 3b Study to Assess the Safety and to Describe the Efficacy of IV Fosnetupitant/Palonosetron (260 mg/0.25 mg) Combination (IV NEPA FDC) Compared to Oral Netupitant/Palonosetron (300 mg/0.5 mg) Combination (Akynzeo®) for the Prevention of Chemotherapy-induced Nausea and Vomiting in Initial and Repeated Cycles of Anthracycline-cyclophosphamide (AC) Chemotherapy in Women With Breast Cancer

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.

Being tested
fosnetupitant/ palonosetron, netupitant/palonosetron, dexamethasone
Medical subject headings
Vomiting

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • fosnetupitant/ palonosetronDrug

    Also called IV NEPA FDC

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

  • netupitant/palonosetronDrug

    Also called Akynzeo capsules

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

  • dexamethasoneDrug

    Oral dexamethasone (12 mg)

Study groups in NCT03403712
Study groupRoleWhat they receive
Test groupExperimentalintravenous 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)
Receives: Drug: fosnetupitant/ palonosetron; Drug: dexamethasone
Control groupActive comparatororal 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)
Receives: Drug: netupitant/palonosetron; Drug: dexamethasone

What is being measured

The primary outcome is the main question the study is designed to answer.

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

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

  2. Number of Participants With Treatment-emergent AEs All Cycles

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

  3. 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

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

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

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

Secondary outcomes (4)

  1. Complete Response in Cycle 1 During the Acute Phase

    defined as no emetic episodes [vomit or retch] and no rescue medication

    Measured: 24 hours after the start of AC chemotherapy administration

  2. Complete Response in Cycle 1 During the Delayed Phase

    defined as no emetic episodes [vomit or retch] and no rescue medication

    Measured: 120 hour after the start of AC chemotherapy administration

  3. Complete Response in Cycle 1 During the Overall Phase

    defined as no emetic episodes [vomit or retch] and no rescue medication

    Measured: 0-120 hours after the start of AC chemotherapy

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

    Percentage (including two-sided 95% CI using Wilson score method) of patients with NIDL based on FLIE scores (overall, by domain, and by individual item) are summarized by treatment group. NIDL was defined as a score greater than 108 points, 54 points, and 6 points for total FLIE score, domain score, and single item score, respectively. Differences between treatment groups for total FLIE score and domain scores (nausea and vomiting) were presented with two-sided 95% CIs using the CMH method adjusted for region and age class strata and also using Newcombe-Wilson's method without strata adjustment.

    No Impact on Daily Life (NIDL) Based on Functional Living Index-Emesis (FLIE) Scores. The FLIE is a nausea and vomiting specific self report instrument comprised of two domains (nausea and vomiting) with nine identical items in each domain

    Measured: cycle 1

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Jan 2018
  2. Study start16 Mar 2018
  3. Primary completion19 Sep 2018
  4. Study completion19 Sep 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
404 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03403712
Sponsor's protocol ID
NEPA-17-05
Status last verified
May 2020
First submitted
4 Jan 2018
Last updated
1 Jun 2020
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • 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.

    PubMed 36527702

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing fosnetupitant/ palonosetron, netupitant/palonosetron and dexamethasone in people with Chemotherapy-induced Nausea and Vomiting, run by Helsinn Healthcare SA at 40 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 46 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 40 sites in United States, Georgia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Apr 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Treatment-emergent AEs at Cycle 1 (time frame: At the end of Cycle 1 (each cycle is 21 days)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03403712, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jun 2020.

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