Clinical Trials List
Protocol NumberML43171
NCT Number(ClinicalTrials.gov Identfier)NCT05306340
Active
2023-06-28 - 2027-03-31
Phase III
Recruiting6
ICD-10C50.011
Malignant neoplasm of nipple and areola, right female breast
ICD-10C50.012
Malignant neoplasm of nipple and areola, left female breast
ICD-10C50.019
Malignant neoplasm of nipple and areola, unspecified female breast
ICD-10Z51.12
Encounter for antineoplastic immunotherapy
ICD-9174.0
Malignant neoplasm of female breast, nipple and areola
A Phase III, Randomized, Open-Label, Multicenter Study Evaluating the Efficacy and Safety of Giredestrant Plus Everolimus Compared With The Physician's Choice of Endocrine Therapy Plus Everolimus in Patients With Estrogen Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer
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Sponsor
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Trial scale
Multi-Regional Multi-Center
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Update
2026/02/01
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Shau-Hsuan Li Division of Hematology & Oncology
- 陳彥仰 Division of Hematology & Oncology
- 李易濰 Division of Hematology & Oncology
- 陳彥豪 Division of Hematology & Oncology
- 陳秉聰 Division of Hematology & Oncology
- Tai-Jan Chiu Division of Hematology & Oncology
- 黃詩喻 Division of Hematology & Oncology
- 吳佳哲 Division of Hematology & Oncology
- 郭明濬 Division of Hematology & Oncology
- Yu-Li Su Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 林季宏 Division of Hematology & Oncology
- WEI-LI MA Division of Hematology & Oncology
- 羅喬 Division of Hematology & Oncology
- 張端瑩 Division of Hematology & Oncology
- 黃柏翔 Division of Hematology & Oncology
- Wei-Wu Chen Division of Hematology & Oncology
- 李佳真 Division of Hematology & Oncology
- 陳怡君 Division of Hematology & Oncology
- MING-YANG WANG Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Wen-Ling Kuo Division of General Surgery
- Wen-Chi Shen Division of Hematology & Oncology
- 張潤忠醫師 Division of Radiology
- 周旭桓 Division of General Surgery
- Mengting Peng Division of Hematology & Oncology
- 何蕙余 Division of General Surgery
- 沈士哲 Division of General Surgery
- 何蕙余醫師 Division of General Surgery
- Chan-Keng Yang Division of Hematology & Oncology
- 張潤忠 Division of Radiology
- Chi-Chang Yu Division of General Surgery
- Yung-Chang Lin Division of Hematology & Oncology
- Pei-Wei Huang Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Chun-Hui Lee
- Jui-Hung Tsai Division of Hematology & Oncology
- Kuo-Ting Lee Division of General Surgery
- Zhu-Jun Loh Division of General Surgery
- Yao-Lung Kuo
- 楊舜如 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Estrogen Receptor (ER)-Positive, HER2-negative, Locally Advanced or Metastatic Breast Cancer
Objectives
This trial will evaluate the efficacy of giredestrant plus everolimus compared with exemestane plus everolimus in patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor type 2 (HER2)-negative locally advanced or metastatic breast cancer. and security.
Test Drug
GIREDESTRANTEVEROLIMUSEXEMESTANETAMOXIFENFULVESTRANT
Active Ingredient
GIREDESTRANT
EVEROLIMUS
EVEROLIMUS
EVEROLIMUS
EXEMESTANE
TAMOXIFEN
FULVESTRANT
EVEROLIMUS
EVEROLIMUS
EVEROLIMUS
EXEMESTANE
TAMOXIFEN
FULVESTRANT
Dosage Form
Hard Capsule
Tablet
Tablet
Tablet
Prefilled syringe
Tablet
Tablet
Tablet
Prefilled syringe
Dosage
30mg
2.5 mg
5 mg
10 mg
25 mg
20MG
50MG/ML
2.5 mg
5 mg
10 mg
25 mg
20MG
50MG/ML
Endpoints
The following efficacy objectives will be assessed in the estrogen receptor 1 mutated subpopulation (ESR1m subpopulation), defined as patients whose tumors harbor a measurable ESR1 mutation in the intention-to-treat (ITT) population, as measured by circulating tumor DNA (ctDNA) and were prospectively classified at baseline, whereas the ITT cohort was defined as all randomized patients.
Co-primary efficacy objective
The co-primary efficacy objectives of this trial are to evaluate the efficacy of giredestrant plus everolimus compared with exemestane plus everolimus in the ESR1m subpopulation and the ITT population based on:
‧ Progression-free survival (PFS), defined as the time from random assignment until the first disease progression or death from any cause (whichever occurs first), as determined by the trial sponsor in accordance with Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST v1.1] The time elapsed until determination)
Co-primary efficacy objective
The co-primary efficacy objectives of this trial are to evaluate the efficacy of giredestrant plus everolimus compared with exemestane plus everolimus in the ESR1m subpopulation and the ITT population based on:
‧ Progression-free survival (PFS), defined as the time from random assignment until the first disease progression or death from any cause (whichever occurs first), as determined by the trial sponsor in accordance with Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST v1.1] The time elapsed until determination)
Inclution Criteria
Inclusion Criteria:
Locally advanced unresectable or metastatic adenocarcinoma of the breast, not amenable to treatment with curative intent
Documented estrogen receptor-positive (ER+) tumor and HER2-negative tumor, assessed locally
Ability to provide a blood sample for circulating-tumor deoxyribonucleic acid (ctDNA) Estrogen Receptor 1 (ESR1) mutation status determination by central testing
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.
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
Eastern Cooperative Oncology Group Performance Status 0-1
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
Locally advanced unresectable or metastatic adenocarcinoma of the breast, not amenable to treatment with curative intent
Documented estrogen receptor-positive (ER+) tumor and HER2-negative tumor, assessed locally
Ability to provide a blood sample for circulating-tumor deoxyribonucleic acid (ctDNA) Estrogen Receptor 1 (ESR1) mutation status determination by central testing
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.
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
Eastern Cooperative Oncology Group Performance Status 0-1
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
Exclusion Criteria
Exclusion Criteria:
Prior treatment with another oral selective estrogen receptor degrader (SERD), proteolysis targeting chimera (PROTAC), complete estrogen receptor antagonist (CERAN), 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.
Progression on more than 2 prior lines of systemic endocrine therapy in the locally advanced unresectable or metastatic breast cancer setting
Prior chemotherapy for locally advanced unresectable or metastatic disease
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
Treatment with any investigational therapy within 28 days prior to initiation of study treatment
Major surgery, chemotherapy, radiotherapy, or other anti-cancer therapy within 14 days prior to randomization
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
Advanced, symptomatic, visceral spread that is at risk of life-threatening complications in the short term
Known active uncontrolled or symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease
Active cardiac disease or history of cardiac dysfunction
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
Active inflammatory bowel disease, chronic diarrhea, short bowel syndrome, or major upper gastrointestinal (GI) surgery including gastric resection
Interstitial lung disease or severe dyspnea at rest or requiring oxygen therapy
Serious infection requiring oral or intravenous (IV) antibiotics, or other clinically significant infection, within 14 days prior to randomization
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
Known allergy or hypersensitivity to any of the study drugs or any of their excipients
For premenopausal or perimenopausal women and for men: known hypersensitivity to LHRH agonists
Pregnant or breastfeeding
Prior treatment with another oral selective estrogen receptor degrader (SERD), proteolysis targeting chimera (PROTAC), complete estrogen receptor antagonist (CERAN), 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.
Progression on more than 2 prior lines of systemic endocrine therapy in the locally advanced unresectable or metastatic breast cancer setting
Prior chemotherapy for locally advanced unresectable or metastatic disease
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
Treatment with any investigational therapy within 28 days prior to initiation of study treatment
Major surgery, chemotherapy, radiotherapy, or other anti-cancer therapy within 14 days prior to randomization
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
Advanced, symptomatic, visceral spread that is at risk of life-threatening complications in the short term
Known active uncontrolled or symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease
Active cardiac disease or history of cardiac dysfunction
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
Active inflammatory bowel disease, chronic diarrhea, short bowel syndrome, or major upper gastrointestinal (GI) surgery including gastric resection
Interstitial lung disease or severe dyspnea at rest or requiring oxygen therapy
Serious infection requiring oral or intravenous (IV) antibiotics, or other clinically significant infection, within 14 days prior to randomization
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
Known allergy or hypersensitivity to any of the study drugs or any of their excipients
For premenopausal or perimenopausal women and for men: known hypersensitivity to LHRH agonists
Pregnant or breastfeeding
The Estimated Number of Participants
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Taiwan
15 participants
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Global
320 participants
