A STUDY TO ASSESS THE EFFICACY AND SAFETY OF GIREDESTRANT COMPARED TO A SUPPORTIVE ENDOCRINE MONOTHERAPY IN ESTROGEN RECEPTOR POSITIVE, HER-2 NEGATIVE EARLY STAGE BREAST CANCER

Argentina, Australia, Austria, Belarus, Belgium, Bosnia and Herzegovina, Brazil, Bulgaria, Canada, Chile, China, Colombia, Costa Rica, Croatia, Czechia, Egypt, Finland, France, Georgia, Germany, Greece, Guatemala, Hong Kong, Hungary, India, Ireland, Israel, Italy, Japan, Kenya, Korea, Republic of, Latvia, Malaysia, Mexico, Netherlands, North Macedonia, Peru, Philippines, Poland, Portugal, Romania, Russian Federation, Serbia, Slovakia, Slovenia, South Africa, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey, Uganda, Ukraine, United Kingdom, United States, Vietnam (ICTRP)

ICTRP Studien-ID
NCT04961996 (ICTRP)

Offizieller Titel (Genehmigt von der Ethikkommission)
A PHASE III, RANDOMIZED, OPEN-LABEL, MULTICENTER STUDY EVALUATING THE EFFICACY AND SAFETY OF ADJUVANT GIREDESTRANT COMPARED WITH PHYSICIAN'S CHOICE OF ADJUVANT ENDOCRINE MONOTHERAPY IN PATIENTS WITH ESTROGEN RECEPTOR-POSITIVE, HER2-NEGATIVE EARLY BREAST CANCER (BASEC)

Wissenschaftlicher Titel
A Phase III, Randomized, Open-Label, Multicenter Study Evaluating the Efficacy and Safety of Adjuvant Giredestrant Compared With Physician's Choice of Adjuvant Endocrine Monotherapy in Patients With Estrogen Receptor-Positive, HER2-Negative Early Breast Cancer (ICTRP)

Öffentlicher Titel
A Study Evaluating the Efficacy and Safety of Adjuvant Giredestrant Compared With Physician's Choice of Adjuvant Endocrine Monotherapy in Participants With Estrogen Receptor-Positive, HER2-Negative Early Breast Cancer (lidERA Breast Cancer) (ICTRP)

Untersuchte Krankheit(en)
Early Breast Cancer (ICTRP)

Untersuchte Intervention
Drug: GiredestrantDrug: Endocrine Therapy of Physician's ChoiceDrug: LHRH AgonistDrug: Abemaciclib (ICTRP)

Studientyp
Interventional (ICTRP)

Studiendesign
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)

Ein-/Ausschlusskriterien
Primary Study Inclusion Criteria:

- Documented estrogen receptor (ER)-positive and HER2-negative breast tumor, as
assessed locally on a primary disease specimen

- Participants who have multicentric (the presence of two of more tumor foci within
different quadrants of the same breast) and/or multifocal (the presence of two or
more tumor foci within a single quadrant of the breast) breast cancer are also
eligible if all examined tumors meet pathologic criteria for ER positivity and HER2
negativity

- Participants must have undergone definitive surgery of their primary breast tumor(s)
and axillary lymph nodes (axillary lymph node dissection [ALND] and/or sentinel
lymph node biopsy [SLNB])

- Participants who received or will be receiving adjuvant chemotherapy must have
completed adjuvant chemotherapy prior to randomization. Participants may also have
received neoadjuvant chemotherapy. A washout period of at least 21 days is required
between last adjuvant chemotherapy dose and randomization.

- Resolution of all acute toxic effects of prior anti-cancer therapy or surgical
procedures to NCI CTCAE v5.0 Grade 1 or better (except alopecia, Grade =2 peripheral
neuropathy, arthralgia or other toxicities not considered a safety risk for the
participant per the investigator's judgment)

- Participants have received (neo)adjuvant chemotherapy and/or had surgery and had no
prior endocrine therapy are eligible, provided that they are enrolled within 12
months following definitive breast cancer surgery

- Participants who have confirmed availability of an untreated primary breast tumor
tissue specimen suitable for biomarker testing (i.e., representative archived
formalin-fixed, paraffin-embedded [FFPE] tissue block [preferred] or 15-20 slides
containing unstained, freshly cut, serial sections), with associated de-identified
pathology report is required. Although 15-20 slides are preferred, if only 10-14
slides are available, the individual may still be eligible for the study.

- Participants with node-positive and node-negative disease are eligible provided they
meet additional risk criteria as defined in the protocol

- Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1, or 2

- Able and willing to swallow, retain, and absorb oral medication

- Adequate organ function

Substudy Inclusion Criteria:

To be eligible for substudy participation, in addition to meeting the inclusion criteria
in the primary protocol, participants must also meet the following modified criteria:

- Patients who received adjuvant radiotherapy must have completed radiotherapy prior
to enrollment, and patients must have recovered (to Grade =1) from the acute effects
of radiotherapy. A washout period of at least 14 days is required between end of
radiotherapy and enrollment.

Primary Study Exclusion Criteria:

- Pregnant or breastfeeding, or intending to become pregnant during the study or
within 10 days after the final dose of giredestrant, or within the time period
specified per local prescribing guidelines after the final dose of the endocrine
therapy of physician's choice

- Received treatment with investigational therapy within 28 days prior to initiation
of study treatment or is currently enrolled in any other type of medical research
judged by the sponsor not to be scientifically or medically compatible with this
study

- Receiving or planning to receive a CDK4/6 inhibitor as (neo)adjuvant therapy. A
short course of up to 12 weeks of neoadjuvant or adjuvant treatment with CDK4/6
inhibitor therapy prior to randomization is allowed.

- Active cardiac disease or history of cardiac dysfunction

- Diagnosed with Stage IV breast cancer

- A history of any prior (ipsilateral and/or contralateral) invasive breast cancer or
ductal carcinoma in situ (DCIS). Participants with a history of contralateral DCIS
treated by only local regional therapy at any time may be eligible.

- A history of any other malignancy within 3 years prior to screening, except for
appropriately treated carcinoma in situ of the cervix, nonmelanoma skin carcinoma,
or Stage I uterine cancer

- Any prior endocrine treatment with selective ER modulators (e.g., tamoxifen),
degraders, or aromatase inhibitors. A short course of neoadjuvant or adjuvant
endocrine therapy (up to 12 weeks) is allowed.

- Clinically significant liver disease consistent with Child-Pugh Class B or C,
including active hepatitis (e.g., hepatitis B virus [HBV] or hepatitis C virus
[HCV]), current alcohol abuse, cirrhosis, or positive test for viral hepatitis

- 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 allergy or hypersensitivity to any of the study drugs or any of their
excipients

- Pre- and perimenopausal participants or male participants who have a known
hypersensitivity to LHRH agonists

- A documented history of hemorrhagic diathesis, coagulopathy, or thromboembolism

- Renal dysfunction that requires dialysis

- A major surgical procedure unrelated to breast cancer within 28 days prior to
randomization

- A serious infection requiring oral or IV antibiotics within 14 days prior to
screening or other clinically significant infection (e.g., COVID-19) within 14 days
prior to screening

- Any serious medical condition or abnormality in clinical laboratory tests that, in
the investigator's judgment, precludes an individual's safe participation in and
completion of the study

- Unable or unwilling to comply with the requirements of the protocol in the opinion
of the investigator

Substudy Exclusion Criteria:

Potential participants are excluded from the substudy if any criteria from t\he primary
study or the following criteria apply:

- Prior participation in the GO42784 primary study

- Received a CDK4/6i as (neo)adjuvant therapy prior to enrollment

- Treatment with moderate CYP3A inducers, strong CYP3A inducers or strong CYP3A
inhibitors within 14 days or 5 drug elimination half-lives (whichever is longer)
prior to initiation of study treatment (ICTRP)

nicht verfügbar

Primäre und sekundäre Endpunkte
Invasive Disease-Free Survival (IDFS), Excluding Second Primary Non-Breast Cancers (ICTRP)

Overall Survival;Invasive Disease-Free Survival (IDFS), Including Second Primary Non-Breast Cancers;Disease-Free Survival (DFS);Distant Recurrence-Free Interval (DRFI);Locoregional Recurrence-Free Interval (LRRFI);Mean Physical Functioning Scale Score at Specified Timepoints, Assessed Using the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30);Change from Baseline in the Mean Physical Functioning Scale Score at Specified Timepoints, Assessed Using the EORTC QLQ-C30;Mean Role Functioning Scale Score at Specified Timepoints, Assessed Using the EORTC QLQ-C30;Change from Baseline in the Mean Role Functioning Scale Score at Specified Timepoints, Assessed Using the EORTC QLQ-C30;Mean Global Health Status/Quality of Life (QoL) Scale Score at Specified Timepoints, Assessed Using the EORTC QLQ-C30;Change from Baseline in the Mean Global Health Status/Quality of Life (QoL) Scale Score at Specified Timepoints, Assessed Using the EORTC QLQ-C30;Change from Baseline in the EQ 5D-5L Index-Based Score at Specified Timepoints;Change from Baseline in the EQ 5D-5L Visual Analogue Scale (VAS) Score at Specified Timepoints;Incidence and Severity of Adverse Events, with Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI-CTCAE v5.0);Plasma Concentrations of Giredestrant at Specified Timepoints;Substudy: Incidence of Grade =3 Adverse Events with Giredestrant in Combination with Abemaciclib;Substudy: Incidence and Severity of Adverse Events with Giredestrant in Combination with Abemaciclib, with Severity Determined According to NCI-CTCAE v5.0 (ICTRP)

Registrierungsdatum
nicht verfügbar

Einschluss des ersten Teilnehmers
nicht verfügbar

Sekundäre Sponsoren
nicht verfügbar

Weitere Kontakte
Clinical Trials;Reference Study ID Number: GO42784 https://forpatients.roche.com/, global-roche-genentech-trials@gene.com, 888-662-6728 (U.S. Only), Hoffmann-La Roche, (ICTRP)

Sekundäre IDs
2021-000129-28, 2023-507172-44-00, GO42784 (ICTRP)

Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten
nicht verfügbar

Weitere Informationen zur Studie
https://clinicaltrials.gov/ct2/show/NCT04961996 (ICTRP)