A Window-of-Opportunity study of hormone therapy in premenopausal women with ER-positive/HER2-negative early breast cancer.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

ETOP IBCSG Partners Foundation

Participant type

Patients

Age range

18-64 years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

29 Jan 2024 → 18 Sep 2025

Decision date (initial)

2024-09-18

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

F. Hoffmann-La Roche Ltd

External identifiers

EU CT number

2022-503013-32-00

ClinicalTrials.gov

NCT05896566

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic

1. 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.
2. 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.

Secondary objectives 1

1.  To assess if 4 weeks of giredestrant without triptorelin provides greater anti-proliferative activity than anastrozole plus triptorelin among premenopausal patients with ER-positive/HER2-negative operable invasive breast cancer.  To assess the safety and tolerability of giredestrant with or without triptorelin over 4 weeks among premenopausal patients with ER-positive/HER2-negative operable invasive breast cancer.

Conditions and MedDRA coding

ER-positive/HER2-negative early breast cancer

Study design 3 periods

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. • Premenopausal women age ≥18 years, premenopausal status defined as: o Estradiol (E2) in the premenopausal range (according to institution parameters) or o 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) o Tumor size must be ≥1.0 cm o 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). o Patients with distant metastatic disease are not eligible. • Documented estrogen receptor (ER)-positive tumor in accordance to American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines, 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, as determined per local assessment. • Ki-67 ≥10% in diagnostic biopsy as determined per local assessment. • Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1. • Resting heart rate ≥40 bpm. • Normal hematologic, renal and liver function • 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 agrees to the submission of tumor (diagnostic core biopsy and re-biopsy) and blood samples for Central Pathology Review (CPR) and for translational studies as part of this protocol. Note: CPR on the primary tumor is mandatory for this trial, but patients will be evaluated for eligibility according to tumor characteristics as determined by the local pathologist. Both the diagnostic breast core biopsy specimen and the specimen from the re-biopsy or from the breast surgery after the WOO treatment is completed must be submitted for CPR, which will be done by the IBCSG Central Pathology Office in Milan, Italy.

Exclusion criteria 1

1. • 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. • History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias. • 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. • Any active tumor of non-breast-cancer histology. • Women who are pregnant or in the period of lactating. • 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

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

Secondary endpoints 1

1.  Complete cell cycle arrest (CCCA), defined as Ki-67 ≤2.7% on post-treatment tumor re-biopsy, by visual image analysis.  Adverse events according to CTCAE v5.0.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

ETOP IBCSG Partners Foundation

Sponsor organisation

ETOP IBCSG Partners Foundation

Address

Effingerstrasse 33

City

Bern

Postcode

3008

Country

Switzerland

Scientific contact point

Organisation

ETOP IBCSG Partners Foundation

Contact name

ETOP IBCSG Partners Regulatory Office

Public contact point

Organisation

ETOP IBCSG Partners Foundation

Contact name

ETOP IBCSG Partners Regulatory Office

Third parties 4

Locations

7 EU/EEA countries · 35 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 66 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

14 submissions — initial application plus substantial / non-substantial modifications