Resumen

This is a Phase III, global, randomized, open-label, multicenter, study evaluating the efficacy and safety of adjuvant giredestrant compared with physician's choice of endocrine therapy in participants with medium- and high-risk Stage I-III histologically confirmed estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative early breast cancer.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

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

Criterios de exclusión

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

Intervenciones

drug

Giredestrant

Giredestrant 30 milligrams (mg) will be administered orally once a day (QD) on Days 1-28 of each 28-day cycle for 5 years or until disease recurrence or unacceptable toxicity (whichever occurs first).

drug

Physician's Choice of Endocrine Therapy

The physician's choice of endocrine therapy (PCET) is limited to tamoxifen or one of the specified third generation aromatase inhibitors: letrozole, anastrozole, or exemestane. Participants will receive PCET daily on Days 1-28 of each 28-day cycle for 5 years or until disease recurrence or unacceptable toxicity (whichever occurs first). Continuing PCET after 5 years is at the discretion of the investigator and per local standard of care. Dose administration of PCET should be performed in accordance with the local prescribing information for the respective product.

drug

LHRH Agonist

A luteinizing hormone-releasing hormone (LHRH) agonist will be administered to male participants and premenopausal/perimenopausal participants according to local prescribing information. The investigator may determine and supply the appropriate LHRH agonist locally approved for use in breast cancer.

Ubicaciones

Centro de Investigaciones Médicas y Desarrollo LC S.R.L

Buenos Aires, Ciudad Autónoma de BuenosAires, Argentina

Fundacion Intectus

Bariloche, Río Negro Province, Argentina

Hospital Italiano Regional del Sur

Bahía Blanca, Argentina

Instituto de Investigaciones Clinicas-Mar del Plata

Buenos Aires, Argentina

Instituto de Investigaciones Metabólicas (IDIM)

Buenos Aires, Argentina

Centro Oncologico Korben

Caba, Argentina

Fundacion Medica de Rio Negro Y Nuequen

Cipolletti, Argentina

Consultorios Médicos Dr. Doreski

Ciudad Autonoma Buenos Aires, Argentina

Sanatorio Allende Servicio Nefrología

Córdoba, Argentina

Centro Medico Privado CEMAIC

Córdoba, Argentina

Centro Oncologico Riojano Integral (CORI)

La Rioja, Argentina

Centro de Investigaciones Medicas Mar Del Plata

Mar del Plata, Argentina

Hospital Privado de La Comunidad

Mar del Plata, Argentina

Centro de Investigacion Pergamino SA

Pergamino, Argentina

Exelsus clinica Oncologica

Provincia de Tucumán, Argentina

Instituto Medico de la Fundacion Estudios Clinicos

Rosario, Argentina

Instituto de Especialidades de la Salud Rosario - Clínica del Tórax

Rosario, Argentina

Sanatorio Parque de Rosario

Rosario, Argentina

Instituto de Oncologia de Rosario

Rosario, Argentina

Centro Polivalente de Asistencia e Investigacion Clinica - CER San Juan

San Juan, Argentina

Centro Médico Privado de Reumatología

San Miguel de Tucumán, Argentina

Organizacion Medica de Investigacion

San Nicolás, Argentina

Fundación Ars Medica

San Salvador de Jujuy, Argentina

Centro de Investigación Clínica ? Clínica Viedma

Viedma, Argentina

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

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Giredestrant

Physician's Choice of Endocrine Therapy

LHRH Agonist

Ubicaciones

Centro de Investigaciones Médicas y Desarrollo LC S.R.L

Fundacion Intectus

Hospital Italiano Regional del Sur

Instituto de Investigaciones Clinicas-Mar del Plata

Instituto de Investigaciones Metabólicas (IDIM)

Centro Oncologico Korben

Fundacion Medica de Rio Negro Y Nuequen

Consultorios Médicos Dr. Doreski

Sanatorio Allende Servicio Nefrología

Centro Medico Privado CEMAIC

Centro Oncologico Riojano Integral (CORI)

Centro de Investigaciones Medicas Mar Del Plata

Hospital Privado de La Comunidad

Centro de Investigacion Pergamino SA

Exelsus clinica Oncologica

Instituto Medico de la Fundacion Estudios Clinicos

Instituto de Especialidades de la Salud Rosario - Clínica del Tórax

Sanatorio Parque de Rosario

Instituto de Oncologia de Rosario

Centro Polivalente de Asistencia e Investigacion Clinica - CER San Juan

Centro Médico Privado de Reumatología

Organizacion Medica de Investigacion

Fundación Ars Medica

Centro de Investigación Clínica ? Clínica Viedma

Patrocinadores