A Window-of-Opportunity Trial of Giredestrant +/- Triptorelin vs. Anastrozole + Triptorelin in Premenopausal Patients With ER-positive/HER2-negative Early Breast Cancer

NCT05896566 | Completed Phase 2 DMC

• 1 other identifier: IBCSG 67-22
• Study Type: interventional
• Target: 231
• Locations: 6 countries
• Sites: 37

Brief 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).

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Change in Ki 67

  The primary endpoint is the change in Ki 67 (Ki 67-labeling index, the percentage immunostaining cells measured by IHC in central laboratory) between the pre-treatment tumor biopsy and a post-treatment tumor re-biopsy (analyzed on the natural logarithm scale).

  From date of randomisation until 29 ±3 days post-randomisation

Secondary Outcomes (2)

• Complete cell cycle arrest (CCCA)

  From date of randomisation until 29 ±3 days post-randomisation

• Adverse events according to CTCAE v5.0

  From the date of enrolment until last patient last visit (approximately 28 months after randomisation of the first patient)]

Study Arms (3)

Arm A: Giredestrant

EXPERIMENTAL

Giredestrant

Drug: Giredestrant

Arm B: Giredestrant plus triptorelin

EXPERIMENTAL

Giredestrant plus triptorelin

Drug: Giredestrant; Drug: Triptorelin

Arm C: Anastrozole plus triptorelin

ACTIVE COMPARATOR

Anastrozole plus triptorelin

Drug: Triptorelin; Drug: Anastrozole

Interventions

Giredestrant DRUG

Giredestrant: 30 mg daily, PO from day 1 until the day of re-biopsy/surgery.

Arm A: Giredestrant; Arm B: Giredestrant plus triptorelin

Anastrozole DRUG

Anastrozole: 1 mg daily, PO from day 1 until the day of re-biopsy/surgery.

Arm C: Anastrozole plus triptorelin

Triptorelin DRUG

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 B: Giredestrant plus triptorelin; Arm C: Anastrozole plus triptorelin

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• ETOP IBCSG Partners Foundation: lead
• Hoffmann-La Roche: collaborator

Study Sites (37)

Gustave Roussy Cancer Center

Villejuif, France

Location

HELIOS Klinikum Berlin Buch

Berlin, Germany

Location

Praxisklinik Krebsheilkunde formerly MediOnko-Institut GbR

Berlin, Germany

Location

KEM / Kliniken Essen Mitte

Essen, Germany

Location

Klinikum der J. W. Goethe Universität

Frankfurt, Germany

Location

Universitätsklinikum Schleswig-Holstein

Kiel, Germany

Location

St. Elisabeth Krankenhaus

Leipzig, Germany

Location

Universitätsklinikum Mannheim GmbH

Mannheim, Germany

Location

Klinikum Südstadt

Rostock, Germany

Location

Universitätsklinikum Ulm

Ulm, Germany

Location

Helios Klinikum Wuppertal GmbH

Wuppertal, Germany

Location

St. James Hospital

Dublin, Ireland

Location

University Hospital Galway

Galway, Ireland

Location

Clinica Oncologica AOU Riuniti Ancona

Ancona, Italy

Location

Humanitas Gavazzeni

Bergamo, Italy

Location

ASL BR Azienda Sanitaria Locale

Brindisi, Italy

Location

IRCCS Ospedale Policlinico San Martino

Genova, Italy

Location

Istituto oncologico romagnolo per lo studio dei tumori "Dino Amadori"

Meldola, Italy

Location

Istituto Europeo di Oncologia

Milan, Italy

Location

AOU maggiore della carita

Novara, Italy

Location

Istituti Clinici Scientifici Maugeri SpA-SB

Pavia, Italy

Location

Azienda USL Toscana Centro

Prato, Italy

Location

Rimini Oncology department

Rimini, Italy

Location

Policlinico universitario Agostino Gemelli IRCCS Rome

Roma, Italy

Location

Institut Catala D'oncologia ICO-Badalona

Badalona, Spain

Location

Institut Catala d'Oncologia - Hospitalet

Barcelona, Spain

Location

CIOCC (Centro Integral Oncológico Clara Campal)

Madrid, Spain

Location

Hospital Universitari Son Espases

Palma de Mallorca, Spain

Location

H. la Fé

Valencia, Spain

Location

Kantonsspital Baden AG

Baden, Switzerland

Location

Praxis Dr. Thorn, Praxis fur ambulante Tumortherapie (Praxis Thorn (Bethesda))

Basel, Switzerland

Location

Onc Inst of Southern Switzerland (IOSI)

Bellinzona, Switzerland

Location

Centre du Sein (Hopital Fribourgeois-Freiburger Spital)

Fribourg, Switzerland

Location

La Chaux-de-fonds, RH Neuchatelois (Hopital Les Cadolles)

La Chaux-de-Fonds, Switzerland

Location

St. Anna Hirslanden

Lucerne, Switzerland

Location

Brustzentrum Thurgau ( Spital AG)

Thurgau, Switzerland

Location

Universitiy Hospital Zurich

Zurich, Switzerland

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

giredestrant; Triptorelin Pamoate; Anastrozole

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Elisabetta Munzone, MD

  European Institute of Oncology, Milano

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: Window of opportunity trial with no therapeutic intent, no efficacy.

Study Record Dates

• First Submitted: May 31, 2023
• First Posted: June 9, 2023
• Study Start: January 23, 2024
• Primary Completion: September 18, 2025
• Study Completion: September 18, 2025
• Last Updated: February 24, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP

Locations

FR (1); DE (10); IE (2); IT (11); ES (5); CH (8)