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

April 4, 2024 updated by: ETOP IBCSG Partners Foundation
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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

220

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • France
      • Villejuif, France
        • Not yet recruiting
        • Gustave Roussy Cancer Center
        • Contact:
          • Barbara Pistilli
  • Germany
  • Hungary
      • Budapest, Hungary
        • Not yet recruiting
        • National Institute of Oncology
        • Contact:
          • Balazs Madaras
  • Ireland
      • Cork, Ireland
        • Not yet recruiting
        • Cork University Hospital
        • Contact:
          • Roisin Connolly
      • Dublin, Ireland
        • Not yet recruiting
        • St. James Hospital
        • Contact:
          • Ciara O'Hanlon Brown
      • Galway, Ireland
        • Not yet recruiting
        • University Hospital Galway
        • Contact:
          • Maccoon Keane
  • Italy
  • Spain
      • Badajoz, Spain
        • Not yet recruiting
        • Complejo Hospitalario Universitario Badajoz
        • Contact:
          • Alba González-Haba Martínez
      • Badalona, Spain
      • Barcelona, Spain
        • Not yet recruiting
        • Institut Catala d'Oncologia - Hospitalet
        • Contact:
          • Verónica Luisa Obadia Gil
      • Lleida, Spain
      • Madrid, Spain
        • Not yet recruiting
        • Fundacion Jimenez Diaz
        • Contact:
      • Madrid, Spain
        • Not yet recruiting
        • CIOCC (Centro Integral Oncológico Clara Campal)
        • Contact:
      • Palma De Mallorca, Spain
      • Valencia, Spain
  • Sweden
      • Gothenburg, Sweden
  • Switzerland
      • Baden, Switzerland
        • Not yet recruiting
        • Kantonsspital Baden AG
        • Contact:
          • Cornelia Leo
      • Basel, Switzerland
        • Recruiting
        • Praxis Dr. Thorn, Praxis fur ambulante Tumortherapie (Praxis Thorn (Bethesda))
        • Contact:
          • David Thorn
      • Bellinzona, Switzerland
        • Not yet recruiting
        • Onc Inst of Southern Switzerland (IOSI)
        • Contact:
          • Lorenzo Rossi
      • Fribourg, Switzerland
        • Not yet recruiting
        • Centre du Sein (Hopital Fribourgeois-Freiburger Spital)
        • Contact:
          • Laurent Rosset
      • La Chaux-de-Fonds, Switzerland
        • Not yet recruiting
        • La Chaux-de-fonds, RH Neuchatelois (Hopital Les Cadolles)
        • Contact:
          • Agnes Auteri
      • Luzern, Switzerland
        • Recruiting
        • St. Anna Hirslanden
        • Contact:
          • Peter Dubsky
      • Thurgau, Switzerland
        • Recruiting
        • Brustzentrum Thurgau ( Spital AG)
        • Contact:
          • Mathias Fehr
      • Zürich, Switzerland
        • Recruiting
        • Universitiy Hospital Zurich
        • Contact:
          • Isabel Witzel

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A: Giredestrant
Giredestrant
Drug: Giredestrant
Giredestrant: 30 mg daily, PO from day 1 until the day of re-biopsy/surgery.
Experimental: Arm B: Giredestrant plus triptorelin
Giredestrant plus triptorelin
Drug: Giredestrant
Giredestrant: 30 mg daily, PO from day 1 until the day of re-biopsy/surgery.
Drug: Triptorelin
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).
Active Comparator: Arm C: Anastrozole plus triptorelin
Anastrozole plus triptorelin
Drug: Triptorelin
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).
Drug: Anastrozole
Anastrozole: 1 mg daily, PO from day 1 until the day of re-biopsy/surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Ki 67
Time Frame: From date of randomisation until 29 ±3 days post-randomisation
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete cell cycle arrest (CCCA)
Time Frame: From date of randomisation until 29 ±3 days post-randomisation
Complete cell cycle arrest (CCCA), defined as Ki 67 ≤2.7% on the post -treatment tumor re-biopsy on day 29 (±3 days), by visual image analysis.
From date of randomisation until 29 ±3 days post-randomisation
Adverse events according to CTCAE v5.0
Time Frame: From the date of enrolment until last patient last visit (approximately 28 months after randomisation of the first patient)]
Record all AEs (including SAEs and AESIs) and assign the appropriate grade according to the CTCAE v5.0.
From the date of enrolment until last patient last visit (approximately 28 months after randomisation of the first patient)]

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

ETOP IBCSG Partners Foundation

Collaborators

Hoffmann-La Roche

Investigators

  • Study Chair: Elisabetta Munzone, MD, European Institute of Oncology, Milano

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 23, 2024

Primary Completion (Estimated)

June 1, 2026

Study Completion (Estimated)

June 1, 2026

Study Registration Dates

First Submitted

May 31, 2023

First Submitted That Met QC Criteria

May 31, 2023

First Posted (Actual)

June 9, 2023

Study Record Updates

Last Update Posted (Actual)

April 5, 2024

Last Update Submitted That Met QC Criteria

April 4, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IBCSG 67-22

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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