Trial Title:
A Window-of-Opportunity Trial of Giredestrant +/- Triptorelin vs. Anastrozole + Triptorelin in Premenopausal Patients With ER-positive/HER2-negative Early Breast Cancer
NCT ID:
NCT05896566
Condition:
Breast Cancer
Conditions: Official terms:
Breast Neoplasms
Anastrozole
Triptorelin Pamoate
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
Window of opportunity trial with no therapeutic intent, no efficacy.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Giredestrant
Description:
Giredestrant: 30 mg daily, PO from day 1 until the day of re-biopsy/surgery.
Arm group label:
Arm A: Giredestrant
Arm group label:
Arm B: Giredestrant plus triptorelin
Intervention type:
Drug
Intervention name:
Triptorelin
Description:
Triptorelin: 3.75 mg IM on day 1. Note: If re-biopsy/surgery cannot be done on day 29 (±3
days) from the first injection, then a second dose of triptorelin should be given on day
29 (±3 days).
Arm group label:
Arm B: Giredestrant plus triptorelin
Arm group label:
Arm C: Anastrozole plus triptorelin
Intervention type:
Drug
Intervention name:
Anastrozole
Description:
Anastrozole: 1 mg daily, PO from day 1 until the day of re-biopsy/surgery.
Arm group label:
Arm C: Anastrozole plus triptorelin
Summary:
PREcoopERA is a randomized (2:2:1), multicenter, open-label, three-arm (A, B, C),
Window-of-Opportunity (WOO) trial to evaluate the activity and safety of giredestrant (A)
versus giredestrant plus triptorelin (B) versus anastrozole plus triptorelin (C).
Detailed description:
The primary objectives are:
- to determine if 4 weeks of giredestrant plus triptorelin provides greater
anti-proliferative activity than anastrozole plus triptorelin among premenopausal
patients with ER-positive/HER2-negative operable invasive breast cancer.
- to determine if 4 weeks of giredestrant without triptorelin provides
anti-proliferative activity that is similar (non-inferior) to giredestrant plus
triptorelin among premenopausal patients with ER-positive/HER2-negative operable
invasive breast cancer.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Premenopausal women age ≥18 years, premenopausal status defined as:
Estradiol (E2) in the premenopausal range (according to institution parameters) or
Patient has been menstruating regularly during the 6 months prior to screening and has
not used any form of hormonal contraception or any other hormonal treatments during this
time.
- Histologically confirmed, operable invasive breast carcinoma.
- Eligible for upfront breast conservative surgery or upfront mastectomy: stage I,
stage II or operable stage III (excludes T4) (AJCC Cancer Staging Manual 8th edition
2017).46 Tumor size must be ≥1.0 cm Multicentric and multifocal tumors and bilateral
breast cancers are allowed but investigators must ensure the same tumor foci is
biopsied pre-treatment and post-treatment (e.g., via clipping of the biopsied tumor
foci).
- Documented estrogen receptor (ER)-positive tumor in accordance to ASCO/CAP
guidelines (Allison et al. 2020),47 assessed locally and defined as ≥1% of tumor
cells stained positive.
- Documented human epidermal growth factor receptor-2 (HER2)-negative tumor in
accordance to 2018 ASCO/CAP guidelines (Wolff et al. 2018)48, as determined per
local assessment.
- Ki 67 ≥10% in diagnostic biopsy as determined per local assessment.
- Eastern Cooperative Oncology Group Performance Status 0-1.
- Resting heart rate ≥40 bpm.
- Normal hematologic status
- Normal renal function
- Normal liver function
- INR <1.5× ULN and PTT <1.5x ULN Except for patients receiving anticoagulation
therapy. For patients receiving warfarin, a stable INR between 2 and 3 is required.
For patients receiving heparin, PTT between 1.5 and 2.5 x ULN (or value before
patient started heparin treatment) is required.
If anticoagulation therapy is required for a prosthetic heart valve, stable INR between
2.5 and 3.5 is permitted.
- Negative serum or urine beta HCG pregnancy test within 5 weeks prior to
randomization.
Pregnancy test will be repeated on day 1, before the first dose of WOO treatment.
Women of childbearing potential must use highly effective contraceptive methods during
the treatment period and for 10 days after the final dose.
- Written Informed Consent (IC) must be signed and dated by the patient and the
Investigator prior to randomization.
- The patient has been informed of and agrees to data transfer and handling, in
accordance with national data protection guidelines.
- The patient agrees to the submission of tumor (diagnostic pre-treatment core biopsy
and post-treatment re-biopsy) and blood samples for central pathology review (CPR)
and for translational studies as part of this protocol.
Exclusion Criteria:
- Stage IV (metastatic) breast cancer.
- Inflammatory breast cancer (cT4d).
- Previous systemic or local treatment for the primary breast cancer currently under
investigation.
- Received any GnRH/LHRH analog within 12 months prior to randomization
- Major surgery within 4 weeks prior to randomization.
- Known clinically significant history of liver disease consistent with Child-Pugh
Class B or C, including hepatitis.
- Other severe acute or chronic medical or psychiatric condition or laboratory
abnormality that may increase the risk associated with study participation or
investigational product administration or may interfere with the interpretation of
study results and, in the judgment of the investigator, would make the patient
inappropriate for entry into this study.
- History of documented hemorrhagic diathesis, coagulopathy, or thromboembolism.
- Active cardiac disease or history of cardiac dysfunction, including any of the
following:
History or presence of symptomatic bradycardia or resting heart rate <50 bpm at
screening. Patients on stable dose of a beta-blocker or calcium channel antagonist for
pre-existing baseline conditions (e.g., hypertension) may be permitted if resting heart
rate is ≥50 bpm.
History of angina pectoris, symptomatic pericarditis, myocardial infarction, or any
cardiac arrhythmias (e.g., ventricular, supraventricular, nodal arrhythmias, or
conduction abnormality) within 12 months prior to study entry History of documented
congestive heart failure (New York Heart Association Class II-IV) or cardiomyopathy Left
ventricular ejection fraction <50% as determined by multiple-gated acquisition scan or
echocardiogram QT interval corrected through use of Fridericia's formula (QTcF) >470 ms
based on mean value of triplicate ECGs, history of long or short QT syndrome, Brugada
syndrome or known history of corrected QT interval prolongation, or torsades de pointes
History or presence of an abnormal ECG that is clinically significant in the
investigator's opinion, including complete left bundle branch block, second- or
third-degree heart block, sick sinus syndrome, or evidence of prior myocardial infarction
- History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias
such as structural heart disease (e.g., severe left ventricular systolic
dysfunction, left ventricular hypertrophy), coronary heart disease (symptomatic or
with ischemia demonstrated by diagnostic testing), clinically significant
electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia, hypocalcemia), or
family history of long QT syndrome.
- Current treatment with medications that are well known to prolong the QT interval.
- Treatment with strong CYP3A4 inhibitors or inducers within 14 days or 5 drug
elimination half-lives (whichever is longer) prior to initiation of study treatment.
- Known issues with swallowing oral medication.
- Active inflammatory bowel disease or chronic diarrhea, short bowel syndrome, or
major upper gastrointestinal surgery including gastric resection.
- Serious infection requiring oral or IV antibiotics, or other clinically significant
infection within 14 days prior to screening.
- Any active tumor of non-breast-cancer histology.
- Women who are pregnant or in the period of lactating.
- Any concurrent disease or serious medical condition or abnormality in clinical
laboratory tests that, in the investigator's judgment, precludes the patient's safe
participation in and completion of the study.
- Judgement by the investigator that the patient should not participate in the study
if the patient is unlikely to comply with study procedures, restrictions and
requirements.
- Contraindications or known hypersensitivity to the trial medication or excipients.
- Treatment with any investigational agents within 30 days prior to expected start of
trial treatment.
Gender:
Female
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Gustave Roussy Cancer Center
Address:
City:
Villejuif
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Barbara Pistilli
Facility:
Name:
HELIOS Klinikum Berlin Buch
Address:
City:
Berlin
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Michael Untch
Email:
michael.untch@helios-gesundheit.de
Facility:
Name:
Praxisklinik Krebsheilkunde formerly MediOnko-Institut GbR
Address:
City:
Berlin
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Oskay Öczelik
Email:
studienoskay@medionko.de
Facility:
Name:
KEM / Kliniken Essen Mitte
Address:
City:
Essen
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Mattea Reinisch
Email:
m.reinisch@kem-med.com
Facility:
Name:
Klinikum der J. W. Goethe Universität
Address:
City:
Frankfurt
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Christine Solbach
Email:
kfg-brustzentrum@kgu.de
Facility:
Name:
Universitätsklinikum Schleswig-Holstein
Address:
City:
Kiel
Country:
Germany
Status:
Not yet recruiting
Contact:
Last name:
Marion van Mackelenbergh
Email:
MarionTina.vanMackelenbergh@uksh.de
Facility:
Name:
St. Elisabeth Krankenhaus
Address:
City:
Leipzig
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Dagmar Langanke
Email:
dagmar.langanke@ek-leipzig.de
Facility:
Name:
Universitätsklinikum Mannheim GmbH
Address:
City:
Mannheim
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Frederik Marme
Email:
Frederik.Marme@umm.de
Facility:
Name:
Klinikum Südstadt
Address:
City:
Rostock
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Toralf Reimer
Email:
toralf.reimer@kliniksued-rostock.de
Facility:
Name:
Universitätsklinikum Ulm
Address:
City:
Ulm
Country:
Germany
Status:
Not yet recruiting
Contact:
Last name:
Brigitte Rack
Email:
Rack_Studien.UFK@uniklinik-ulm.de
Facility:
Name:
Helios Klinikum Wuppertal GmbH
Address:
City:
Wuppertal
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Vesna Bjelic-Radisic
Email:
Vesna.Bjelic-Radisic@helios-gesundheit.de
Facility:
Name:
National Institute of Oncology
Address:
City:
Budapest
Country:
Hungary
Status:
Recruiting
Contact:
Last name:
Balazs Madaras
Facility:
Name:
Cork University Hospital
Address:
City:
Cork
Country:
Ireland
Status:
Not yet recruiting
Contact:
Last name:
Roisin Connolly
Facility:
Name:
St. James Hospital
Address:
City:
Dublin
Country:
Ireland
Status:
Recruiting
Contact:
Last name:
Ciara O'Hanlon Brown
Facility:
Name:
University Hospital Galway
Address:
City:
Galway
Country:
Ireland
Status:
Not yet recruiting
Contact:
Last name:
Maccoon Keane
Facility:
Name:
Clinica Oncologica AOU Riuniti Ancona
Address:
City:
Ancona
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Rossana Berardi
Email:
Rossana.Berardi@ospedaliriuniti.marche.it
Facility:
Name:
Humanitas Gavazzeni
Address:
City:
Bergamo
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Fabio Conforti
Email:
fabio.conforti@gavazzeni.it
Facility:
Name:
ASL BR Azienda Sanitaria Locale
Address:
City:
Brindisi
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Saverio Cinieri
Email:
saverio.cinieri@asl.brindisi.it
Facility:
Name:
IRCCS Ospedale Policlinico San Martino
Address:
City:
Genova
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Matteo Lambertini
Email:
matteo.lambertini@unige.it
Facility:
Name:
Istituto oncologico romagnolo per lo studio dei tumori "Dino Amadori"
Address:
City:
Meldola
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Ugo De Giorgi
Email:
ugo.degiorgi@irst.emr.it
Facility:
Name:
Istituto Europeo di Oncologia
Address:
City:
Milano
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Elisabetta Munzone
Email:
elisabetta.munzone@ieo.it
Facility:
Name:
AOU maggiore della carita
Address:
City:
Novara
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Alessandra Gennari
Email:
alessandra.gennari@med.uniupo.it
Facility:
Name:
Istituti Clinici Scientifici Maugeri SpA-SB
Address:
City:
Pavia
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Laura Deborah Locati
Email:
lauradeborah.locati@icsmaugeri.it
Facility:
Name:
Azienda USL Toscana Centro
Address:
City:
Prato
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Laura Biganzoli
Email:
laura.biganzoli@uslcentro.toscana.it
Facility:
Name:
Rimini Oncology department
Address:
City:
Rimini
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Lorenzo Gianni
Email:
lorenzo.gianni@auslromagna.it
Facility:
Name:
Fondazione Policlinico Gemelli Medical Oncology Unit
Address:
City:
Roma
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Emilio Bria
Email:
emilio.bria@policlinicogemelli.it
Facility:
Name:
Policlinico universitario Agostino Gemelli IRCCS Rome
Address:
City:
Roma
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Alessandra Fabi
Email:
alessandra.fabi@policlinicogemelli.it
Facility:
Name:
Complejo Hospitalario Universitario Badajoz
Address:
City:
Badajoz
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Alba González-Haba Martínez
Facility:
Name:
Institut Catala D'oncologia ICO-Badalona
Address:
City:
Badalona
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Milana Bergamino
Email:
milana.bergamino@iconcologia.net
Facility:
Name:
Institut Catala d'Oncologia - Hospitalet
Address:
City:
Barcelona
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Verónica Luisa Obadia Gil
Facility:
Name:
H.U. Arnau de Vilanova de Lleida
Address:
City:
Lleida
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Serafín Morales
Email:
smorales.lleida.ics@gencat.cat
Facility:
Name:
CIOCC (Centro Integral Oncológico Clara Campal)
Address:
City:
Madrid
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Beatriz Rojas Garcia
Email:
Beatrizrojas1981@gmail.com
Facility:
Name:
Fundación Jiménez Díaz
Address:
City:
Madrid
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Yann Izarzugaza
Email:
yizarzugaza@fjd.es
Facility:
Name:
Hospital Universitari Son Espases
Address:
City:
Palma De Mallorca
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Antonia Perello
Email:
antonia.perellom@ssib.es
Facility:
Name:
H. la Fé
Address:
City:
Valencia
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Helena de la Cueva
Email:
delacueva_hel@gva.es
Facility:
Name:
Sahlgrenska Comprehensive Cancer Center
Address:
City:
Gothenburg
Country:
Sweden
Status:
Recruiting
Contact:
Last name:
Per Karlsson
Email:
per.karlsson@oncology.gu.se
Facility:
Name:
Kantonsspital Baden AG
Address:
City:
Baden
Country:
Switzerland
Status:
Recruiting
Contact:
Last name:
Cornelia Leo
Facility:
Name:
Praxis Dr. Thorn, Praxis fur ambulante Tumortherapie (Praxis Thorn (Bethesda))
Address:
City:
Basel
Country:
Switzerland
Status:
Recruiting
Contact:
Last name:
David Thorn
Facility:
Name:
Onc Inst of Southern Switzerland (IOSI)
Address:
City:
Bellinzona
Country:
Switzerland
Status:
Recruiting
Contact:
Last name:
Lorenzo Rossi
Facility:
Name:
Centre du Sein (Hopital Fribourgeois-Freiburger Spital)
Address:
City:
Fribourg
Country:
Switzerland
Status:
Recruiting
Contact:
Last name:
Laurent Rosset
Facility:
Name:
La Chaux-de-fonds, RH Neuchatelois (Hopital Les Cadolles)
Address:
City:
La Chaux-de-Fonds
Country:
Switzerland
Status:
Recruiting
Contact:
Last name:
Agnes Auteri
Facility:
Name:
St. Anna Hirslanden
Address:
City:
Luzern
Country:
Switzerland
Status:
Recruiting
Contact:
Last name:
Peter Dubsky
Facility:
Name:
Brustzentrum Thurgau ( Spital AG)
Address:
City:
Thurgau
Country:
Switzerland
Status:
Recruiting
Contact:
Last name:
Mathias Fehr
Facility:
Name:
Universitiy Hospital Zurich
Address:
City:
Zürich
Country:
Switzerland
Status:
Recruiting
Contact:
Last name:
Isabel Witzel
Start date:
January 23, 2024
Completion date:
June 1, 2026
Lead sponsor:
Agency:
ETOP IBCSG Partners Foundation
Agency class:
Other
Collaborator:
Agency:
Hoffmann-La Roche
Agency class:
Industry
Source:
ETOP IBCSG Partners Foundation
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05896566
