A Study Evaluating the Efficacy and Safety of Giredestrant Compared With Physician's Choice of Endocrine Monotherapy in Participants With Previously Treated Estrogen Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer (acelERA Breast Cancer)
- Conditions
- Estrogen Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer
- Interventions
- Registration Number
- NCT04576455
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This Phase II, randomized, open-label, multicenter study will evaluate the efficacy and safety of giredestrant compared with physician's choice of endocrine monotherapy in participants with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer who have received one or two prior lines of systemic therapy in the locally advanced or metastatic setting.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 303
- Women who are postmenopausal or premenopausal/perimenopausal
- For women who are premenopausal or perimenopausal and for men: willing to undergo and maintain treatment with approved LHRH agonist therapy for the duration of study treatment
- Locally advanced or metastatic adenocarcinoma of the breast, not amenable to treatment with curative intent
- Documented ER-positive tumor and HER2-negative tumor, assessed locally
- Disease progression after treatment with one or two lines of systemic therapy (but not more than one prior targeted therapy) in the locally advanced or metastatic setting
- Measurable disease as defined per RECIST v.1.1 or bone only disease which must have at least one predominantly lytic bone lesion confirmed by CT or MRI which can be followed
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
- Adequate organ function
- Prior treatment with a selective estrogen receptor degrader (SERD), with the exception of fulvestrant, if fulvestrant treatment was terminated at least 28 days prior to randomization
- Treatment with any investigational therapy within 28 days prior to randomization
- Advanced, symptomatic, visceral spread that is at risk of life-threatening complications
- Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease
- Active cardiac disease or history of cardiac dysfunction
- Pregnant or breastfeeding
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Giredestrant Giredestrant - Giredestrant LHRH Agonist - Physician Choice of Endocrine Monotherapy Fulvestrant or an Aromatase Inhibitor (Physician Choice) The physician choice of endocrine monotherapy will be limited to fulvestrant or an aromatase inhibitor. Physician Choice of Endocrine Monotherapy LHRH Agonist The physician choice of endocrine monotherapy will be limited to fulvestrant or an aromatase inhibitor.
- Primary Outcome Measures
Name Time Method Progression-Free Survival (PFS), as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to a clinical cutoff of 15 months) PFS was defined as the time from randomization to the first occurrence of disease progression as determined by the investigator according to RECIST v1.1, or death from any cause (whichever occurs first). Disease progression was defined as ≥20% increase in the sum of diameters of target lesions, unequivocal progression in non-target lesions, and/or appearance of new lesions.
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) From randomization to death from any cause (up to approximately 36 months) OS is defined as the time from randomization to death from any cause.
Duration of Response (DOR), as Determined by the Investigator According to RECIST v1.1 From first occurrence of documented objective response to disease progression or death from any cause, whichever occurs first (up to approximately 36 months) DOR is defined as the time from the first occurrence of a documented objective response to disease progression as determined by the investigator according to RECIST v1.1 or death from any cause (whichever occurs first). Objective response rate is defined as the percentage of participants with a CR or PR on two consecutive occasions at least 4 weeks apart. Per RECIST v1.1, CR is defined as disappearance of all target and non-target lesions. Any pathological lymph nodes must have reduction in short axis to \<10 millimeters (mm). PR is defined as at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. Disease progression is defined as ≥20% increase in the sum of diameters of target lesions, unequivocal progression in non-target lesions, and/or appearance of new lesions.
Investigator-Assessed PFS, in Subgroups Categorized by Estrogen Receptor 1 (ESR1) Mutation Status From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to a clinical cutoff of 15 months) PFS was defined as the time from randomization to the first occurrence of disease progression determined by the investigator according to RECIST v1.1 or death from any cause (whichever occurs first). Disease progression was defined as ≥20% increase in in the sum of diameters of target lesions, unequivocal progression in non-target lesions, and/or appearance of new lesions. Investigator-assessed PFS was analyzed in subgroups categorized by baseline ESR1 mutation status (i.e., with or without ESR1 mutation at baseline) from plasma circulating tumor deoxyribonucleic acid (ctDNA).
Time to Deterioration (TTD) in Pain Severity From Baseline until treatment discontinuation (up to approximately 36 months) TTD in pain severity is defined as time to first documented ≥2-point increase from Baseline in the "Worst Pain" item from the Brief Pain Inventory-Short Form (BPI-SF) Questionnaire. The BPI-SF is a self administered questionnaire developed to assess the severity of pain (the sensory dimension) as well as the degree to which pain interferes with function (the reactive dimension). The BPI-SF uses 10-point numeric rating scale, with 0="No pain", "No interference" to 10="Pain as bad as you can imagine", "Highest imaginable interference". A lower score indicates improvement.
TTD in Physical Functioning (PF) From Baseline until treatment discontinuation (up to approximately 36 months) TTD in PF is defined as the time to first documented ≥10-point decrease from baseline in the EORTC QLQ-C30 linearly transformed PF scale score. EORTC QLQ-C30 is a validated and reliable self-report measure that consists of 30 questions assessing five aspects of participant functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), global health and quality of life, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties) with a recall period of the previous week. The PF scale has 5 questions about participants' physical functioning and is scored on a 4-point scale (1=Not at All to 4=Very Much). The obtained scores are linearly transformed to a score range of 0-100, where higher scores indicate a higher response level (better physical function).
Objective Response Rate, as Determined by the Investigator According to RECIST v1.1 From randomization until disease progression or death (up to approximately 36 months) The objective response rate is defined as the percentage of participants with a complete response (CR) or partial response (PR) on two consecutive occasions at least 4 weeks apart. Per RECIST v1.1, CR is defined as disappearance of all target and non-target lesions. Any pathological lymph nodes must have reduction in short axis to \<10 millimeters (mm). PR is defined as at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR.
Clinical Benefit Rate, as Determined by the Investigator According to RECIST v1.1 From randomization until disease progression or death (up to approximately 36 months) The clinical benefit rate is defined as the percentage of participants with stable disease for ≥24 weeks or a CR or PR. Per RECIST v1.1, CR is defined as disappearance of all target and non-target lesions. Any pathological lymph nodes must have reduction in short axis to \<10 millimeters (mm). PR is defined as at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR.
TTD in Pain Presence and Interference, Defined as Time to First Documented ≥10-Point Increase From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 Linearly Transformed Pain Scale Score From Baseline until treatment discontinuation (up to approximately 36 months) EORTC QLQ-C30 is a validated and reliable self-report measure that consists of 30 questions assessing five aspects of participant functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), global health and quality of life, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties) with a recall period of the previous week. The functioning and symptoms items are scored on a 4-point scale that ranges from 1=not at all to 4=very much. The Pain scale is scored on a 4-point scale (1=Not at All to 4=Very Much). The obtained scores are linearly transformed to a score range of 0-100, where higher scores indicate worse pain symptoms.
TTD in Role Functioning (RF) From Baseline until treatment discontinuation (up to approximately 36 months) TTD in RF is defined as the time to first documented ≥10-point decrease from baseline in the EORTC QLQ-C30 linearly transformed RF scale score. EORTC QLQ-C30 is a validated and reliable self-report measure that consists of 30 questions that assessing five aspects of participant functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), global health and quality of life, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties) with a recall period of the previous week. The RF scale is scored on a 4-point scale (1=Not at All to 4=Very Much). The obtained scores are linearly transformed to a score range of 0-100, where higher scores indicate better functioning/support.
Number of Participants With Vital Sign Abnormalities Over the Course of the Study Assessed at Baseline and predose on Day 1 of every cycle (1 cycle is 28 days) until 30 days after the final dose of study drug (up to approximately 36 months) Vital signs include respiratory rate, pulse rate, systolic and diastolic blood pressure while the patient is in a seated position, and temperature.
TTD in Global Health Status and Quality of Life (GHS/QoL) From Baseline until treatment discontinuation (up to approximately 36 months) TTD in GHS/QoL is defined as the time to first documented ≥10-point decrease from baseline in the EORTC QLQ-C30 linearly transformed GHS/QoL scale score. EORTC QLQ-C30 is a validated and reliable self-report measure that consists of 30 questions that assessing five aspects of participant functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), global health and quality of life, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties) with a recall period of the previous week. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). The obtained scores are linearly transformed to a score range of 0-100, where higher scores indicate a better QoL.
Plasma Concentration of Giredestrant at Specified Timepoints Predose and postdose on Day 1 of Cycles 1 and 2, predose on Day 1 of Cycles 3, 5, 7, 9, 11, 13, and 15 (1 cycle is 28 days), and 30 days after final dose of study drug (up to approximately 36 months) Number of Participants With Adverse Events (AEs), Severity Determined According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) From Baseline until 30 days after final dose of study drug (up to approximately 36 months) An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product; any new disease or exacerbation of an existing disease; recurrence of an intermittent medical condition; any deterioration in a laboratory value or other clinical test; AEs that are related to a protocol-mandated intervention, including those that occur prior to assignment of study treatment.
Number of Participants With Clinical Laboratory Test Abnormalities for Hematology Parameters Over the Course of the Study Assessed at Baseline and predose on Day 1 of every cycle (1 cycle is 28 days) until 30 days after the final dose of study drug (up to approximately 36 months) Hematology parameters include white blood cell (WBC) count, red blood cell (RBC) count, hemoglobin, hematocrit, platelet count, and differential count (neutrophils, eosinophils, basophils, monocytes, lymphocytes, other cells).
Number of Participants With Clinical Laboratory Test Abnormalities for Biochemistry Parameters Over the Course of the Study Assessed at Baseline and predose on Day 1 of every cycle (1 cycle is 28 days) until 30 days after the final dose of study drug (up to approximately 36 months) Biochemistry parameters include bicarbonate or total carbon dioxide, sodium, potassium, chloride, glucose, blood urea nitrogen (BUN) or urea, creatinine, total protein, albumin, phosphate, calcium, total and direct bilirubin, alkaline phosphatase level test (ALP), Alanine transaminase (ALT), aspartate aminotransferase (AST), urate, and lactate dehydrogenase (LDH).
Trial Locations
- Locations (84)
Cancercare Langenhoven Drive Oncology Centre
🇿🇦Port Elizabeth, South Africa
Eastleigh Breast Care Centre
🇿🇦Pretoria, South Africa
Changhua Christian Hospital; Dept of Surgery
🇨🇳Changhua, Taiwan
Ramathibodi Hospital; Dept of Med.-Div. of Med. Onc
🇹🇭Bangkok, Thailand
Maharaj Nakorn Chiang Mai Hosp; Surgery/Oncology
🇹🇭Chang Mai, Thailand
Songklanagarind Hospital; Department of Oncology
🇹🇭Songkhla, Thailand
Instituto Angel Roffo
🇦🇷Ciudad Autonoma Buenos Aires, Argentina
Fundación Scherbovsky; General Department
🇦🇷Mendoza, Argentina
Hosp Provincial D. Centenarios; Oncology Dept
🇦🇷Rosario, Argentina
Organizacion Medica de Investigacion
🇦🇷San Nicolás, Argentina
National Cheng Kung Uni Hospital; Dept of Hematology and Oncology
🇨🇳Tainan, Taiwan
Chi-Mei Medical Centre; Hematology & Oncology
🇨🇳Tainan, Taiwan
VETERANS GENERAL HOSPITAL; Department of General Surgery
🇨🇳Taipei, Taiwan
Chang Gung Memorial Hosipital at Linkou
🇨🇳Taoyuan City, Taiwan
Chulalongkorn Hospital; Medical Oncology
🇹🇭Bangkok, Thailand
Memorial Ankara Hastanesi
🇹🇷Ankara, Turkey
Rajavithi Hospital; Division of Medical Oncology
🇹🇭Bangkok, Thailand
Ankara City Hospital; Oncology
🇹🇷Ankara, Turkey
Memorial Antalya Hospital
🇹🇷Antalya, Turkey
Dicle University Faculty of Medicine
🇹🇷Diyarbakir, Turkey
Prof. Dr. Cemil Tascioglu City Hospital; Med Onc
🇹🇷Istanbul, Turkey
Kartal Dr Lutfi Kirdar Sehir Hastanesi; Medical Oncology Department
🇹🇷Istanbul, Turkey
Katip Celebi University Ataturk Training and Research Hospital; Oncology
🇹🇷Izmir, Turkey
Medikal Park Samsun
🇹🇷Samsun, Turkey
Zhytomyr Regional Oncology Center
🇺🇦Zhytomyr, KIEV Governorate, Ukraine
Kyiv City Clinical Oncological Center
🇺🇦Kyiv, Ukraine
MI Kyiv Regional Council Kyiv Regional Oncological Dispensary; Department of Mammology
🇺🇦Kyiv, Ukraine
RCI Sumy Regional Clinical Oncological Dispensary
🇺🇦Sumy, Ukraine
Princess Alexandra Hospital; Oncology Department
🇬🇧Harlow, United Kingdom
Guys & St Thomas Hospital; Department of Oncology
🇬🇧London, United Kingdom
Nottingham City Hospital; Oncology
🇬🇧Nottingham, United Kingdom
Peterborough City Hospital; Oncology Research Department 018
🇬🇧Peterborough, United Kingdom
Northwest Georgia Oncology Centers PC - Marietta
🇺🇸Marietta, Georgia, United States
University Hospitals Seidman Cancer Center
🇺🇸Cleveland, Ohio, United States
Northwest Cancer Specialists - Portland (SW Barnes Rd)
🇺🇸Tigard, Oregon, United States
Fundación CENIT para la Investigación en Neurociencias
🇦🇷Buenos Aires, Argentina
Kinghorn Cancer Centre; St Vincents Hospital
🇦🇺Darlinghurst, New South Wales, Australia
Sunshine Hospital
🇦🇺St Albans, Victoria, Australia
Pronutrir - suporte nutricional e quimioterapia ltda.
🇧🇷Fortaleza, CE, Brazil
Oncosite - Centro de Pesquisa Clinica Em Oncologia Ltda
🇧🇷Ijui, RS, Brazil
Santa Casa de Misericordia de Porto Alegre
🇧🇷Porto Alegre, RS, Brazil
Clinica de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria Ltda
🇧🇷Sao Paulo, SP, Brazil
Núcleo de Pesquisa São Camilo; ONCOLOGIA CLINICA / QUIMIOTERAPIA
🇧🇷Sao Paulo, SP, Brazil
The First Hospital of Jilin University
🇨🇳Changchun City, China
Sun Yet-sen University Cancer Center
🇨🇳Guangzhou City, China
Harbin Medical University Cancer Hospital
🇨🇳Harbin, China
Linyishi Cancer Hospital
🇨🇳Linyi City, China
The Third Hospital of Nanchang
🇨🇳Nanchang City, China
Fudan University Shanghai Cancer Center
🇨🇳Shanghai City, China
Tianjin Cancer Hospital
🇨🇳Tianjin, China
Hubei Cancer Hospital
🇨🇳Wuhan, China
First Affiliated Hospital of Medical College of Xi'an Jiaotong University
🇨🇳Xi'an, China
Zhejiang Cancer Hospital
🇨🇳Zhejiang, China
Hämato-Onkologische Schwerpunktpraxis am Klinikum Aschaffenburg
🇩🇪Aschaffenburg, Germany
Frauenarzt-Zentrum Zehlendorf an der Teltower Eiche
🇩🇪Berlin, Germany
Kooperatives Mammazentrum Hamburg Krankenhaus Jerusalem
🇩🇪Hamburg, Germany
St. Vincenz-Krankenhaus Paderborn; Haus 3 Frauenklinik
🇩🇪Paderborn, Germany
Gynäkologie Kompetenzzentrum; Praxis Dr. med. Carsten Hielscher
🇩🇪Stralsund, Germany
Assuta Medical Center- Ashdod; Oncology
🇮🇱Ashdod, Israel
Hadassah Ein Karem Hospital; Oncology Dept
🇮🇱Jerusalem, Israel
Meir Medical Center; Oncology
🇮🇱Kfar-Saba, Israel
Soon Chun Hyang University Cheonan Hospital
🇰🇷Dongnam-gu, Cheonan-si, Korea, Republic of
National Cancer Center
🇰🇷Goyang-si, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Gangnam Severance Hospital
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Seoul St Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Narodowy Instytut Onkologii Odzia? w Gliwicach; Centrum Diagnostyki i Leczenia Chorób Piersi
🇵🇱Gliwice, Poland
Bialostockie Centrum Onkologii; Oddzial Onkologii Klinicznej
🇵🇱Bialystok, Poland
Narodowy Inst.Onkologii im.Sklodowskiej-Curie Panstw.Inst.Bad; Klinika Nowtw.Piersi i Chir.Rekonstr
🇵🇱Warszawa, Poland
Krasnoyarsk Regional Oncology Dispensary n.a. Krizhanovsky; Chemotherapy
🇷🇺Krasnoyarsk, Krasnodar, Russian Federation
Blokhin Cancer Research Center; Combined Treatment
🇷🇺Moskva, Moskovskaja Oblast, Russian Federation
Filial #1 Regional Oncology Dispensary of Nizhniy Novgorod
🇷🇺Nizhny Novgorod, Niznij Novgorod, Russian Federation
St. Petersburg SHI "City Clinical Oncology Dispensary"
🇷🇺Sankt-peterburg, Sankt Petersburg, Russian Federation
Republican Clinical Oncology Dispensary of Ministry of Healthcare of Tatarstan Republic
🇷🇺Kazan, Tatarstan, Russian Federation
Clinical Oncology Centre # 1; Chemotherapy Dept
🇷🇺Krasnodar, Russian Federation
Multidisciplinary clinic Reaviz
🇷🇺Samara, Russian Federation
Petrov Research Inst. of Oncology
🇷🇺Sankt Petersburg, Russian Federation
Volgograd Regional Clinical Oncology Dispensary
🇷🇺Volgograd, Russian Federation
National University Hospital; National University Cancer Institute, Singapore (NCIS)
🇸🇬Singapore, Singapore
Regional Clinical Oncology Hospital
🇷🇺Yaroslavl, Russian Federation
Iatros International
🇿🇦Bloemfontein, South Africa