A Study Evaluating the Efficacy and Safety of Giredestrant Plus Everolimus Compared With The Physician's Choice of Endcrine Therapy Plus Everolimus in Participants With Estrogen Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer (evERA Breast Cancer)

JRCT ID: jRCT2061220101

Registered date:28/02/2023

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Estrogen Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer
• Date of first enrollment: 26/04/2023
• Target sample size: 320
• Countries of recruitment: United States,Japan,United Kingdom,Japan,Argentina,Japan,Korea,Japan,Taiwan,Japan,Spain,Japan,Singapore,Japan,Greece,Japan,Germany,Japan,Italy,Japan,South Africa,Japan,Turkey,Japan
• Study type: Interventional

Intervention(s)

Giredestrant: 30 milligrams (mg) by mouth (PO) once a day (QD) during each 28-day
Everolimus: 10 mg PO QD during each 28-day cycle
Exemestane: 25 mg PO QD during each 28-day cycle
Fulvestrant: 500 mg intramuscularly on Day 1 and Day 15 of Cycle 1, then Day 1 of each cycle thereafter (1 cycle is 28 days)
Tamoxifen: 20 mg orally QD on Days 1-28 of each 28-day cycle

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 approriate LHRH agonist locally approved for use in brest cancer.

Outcome(s)

Primary Outcome

Efficacy
Progression-Free Survival, as Determined by the Investigator According to RECIST v1.1, in the ESR1m Subpopulation and ITT Population [ Time Frame: From randomization until the first occurrence of disease progression or death from any cause, whichever occurs first (up to 42 months) ]

Secondary Outcome

Safety, Efficacy, Phamacokinetics
1 Overall Survival, in the ESR1m Subpopulation and ITT Population
2 Objective response rate, RECIST v1.1
3 Duration of response, RECIST v1.1
4 Clinical benefit rate, RECIST v1.1
5 Time to confirmed deterioration, BPI-SF Questionnaire
6 TTCD in pain presence and interference after randomization, EORTC QLQ-C30
7 TTCD in Physical Functioning (PF), the EORTC QLQ-C30
8 TTCD in Role Functioning (RF), the EORTC QLQ-C30
9 TTCD in health-related quality of life (HRQoL), the EORTC QLQ-C30
10 Number of Participants with at Least One Adverse Event,(NCI CTCAE v5.0
11 Number of Participants with Vital Sign Abnormalities Over the Course of the Study
12 Number of Participants with Clinical Laboratory Test Abnormalities for Hematology Parameters Over the Course of the Study
13 Number of Participants with Clinical Laboratory Test Abnormalities for Biochemistry Parameters Over the Course of the Study
14 Plasma Concentration of Giredestrant at Specified Timepoints

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1 Locally advanced unresectable or metastatic adenocarcinoma of the breast, not amenable to treatment with curative intent
2 Documented estrogen receptor-positive (ER+) tumor and HER2-negative tumor, assessed locally
3 Ability to provide a blood sample for circulating-tumor deoxyribonucleic acid (ctDNA) Estrogen Receptor 1 (ESR1) mutation status determination by central testing
4 Prior endocrine therapy (ET) in combination with cyclin-dependent kinase 4/6 inhibitors in either setting as follows:
-Metastatic setting: Disease progression after >=6 months on ET plus CDK4/6 inhibitor in the locally advanced or metastatic setting. If ET plus CDK4/6 inhibitor is not the most recent therapy, then patient must also have had disease progression after >=4 months on most recent ET
-Adjuvant Setting: Relapse either while taking or within 12 months of exposure to combination adjuvant ET and CDK4/6 inhibitor. Patients must have taken at least 12 months of adjuvant ET, 6 months of which was in combination with a CDK4/6 inhibitor.
5 Measurable disease as defined per RECIST v.1.1 or evaluable bone metastases. Patients with evaluable bone disease in the absence of measurable disease outside of the bone must have at least one predominantly lytic bone lesion confirmed by computed tomography (CT) or magnetic resonance imaging (MRI) which can be followed
6 Eastern Cooperative Oncology Group Performance Status 0-1
7 For women who are premenopausal or perimenopausal and for men: treatment with approved luteinizing hormone-releasing hormone (LHRH) agonist therapy for the duration of the study treatment

Exclude criteria

1 Prior treatment with another oral selective estrogen receptor degrader (SERD), proteolysis targeting chimera (PROTAC), complete estrogen receptor antagonist (CERAN), or novel oral selective estrogen receptor modulator (SERM), or everolimus in any setting. Prior fulvestrant is allowed if treatment was terminated at least 28 days prior to randomization.Prior treatment with tamoxifen is allowed.
2 Progression on no more than 2 prior lines of systemic endocrine therapy in the locally advanced unresectable or metastatic breast cancer setting
3 Prior chemotherapy for locally advanced unresectable or metastatic disease
4 Treatment with strong Cytochrome P450 3A4 (CYP3A4) inhibitors or inducers within 14 days or 5 drug elimination half-lives (whichever is longer) prior to randomization
5 Treatment with any investigational therapy within 28 days prior to initiation of study treatment
6 Major surgery, chemotherapy, radiotherapy, or other anti-cancer therapy within 14 days prior to randomization
7 History of any other malignancy other than breast cancer within 5 years prior to screening, except for appropriately treated carcinoma in situ of the cervix, nonmelanoma skin carcinoma, papillary thyroid cancer treated with surgery, Stage I endometrial cancer, or other non-breast cancers at very low risk of recurrence
8 Advanced, symptomatic, visceral spread that is at risk of life-threatening complications in the short term
9 Known active uncontrolled or symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease
10 Active cardiac disease or history of cardiac dysfunction
11 Known clinically significant history of liver disease consistent with Child-Pugh Class B or C including active viral or other hepatitis virus, current alcohol abuse, or cirrhosis
12 Active inflammatory bowel disease, chronic diarrhea, short bowel syndrome, or major upper gastrointestinal (GI) surgery including gastric resection
13 Interstitial lung disease or severe dyspnea at rest or requiring oxygen therapy
14 Serious infection requiring oral or intravenous (IV) antibiotics, or other clinically significant infection, within 14 days prior to randomization
15 Any 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
16 Known allergy or hypersensitivity to any of the study drugs or any of their excipients
17 For premenopausal or perimenopausal women and for men: known hypersensitivity to LHRH agonists
18 Pregnant or breastfeeding

Related Information

• Primary Sponsor: Patricia Cortazar, M.D.
• Secondary ID(s): NCT05306340