Clinical trial NCT04576455: 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)
Official title: A Phase II, Randomized, Open-Label, Multicenter Study Evaluating the Efficacy and Safety of GDC-9545 Compared With Physician's Choice of Endocrine Monotherapy in Patients With Previously Treated Estrogen Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Estrogen Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2020-10-06
Enrollment: 303
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Progression-Free Survival (PFS), as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
timeFrame: 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)
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: From randomization to death from any cause (up to approximately 36 months)
measure: Objective Response Rate, as Determined by the Investigator According to RECIST v1.1
timeFrame: From randomization until disease progression or death (up to approximately 36 months)
measure: Duration of Response (DOR), as Determined by the Investigator According to RECIST v1.1
timeFrame: From first occurrence of documented objective response to disease progression or death from any cause, whichever occurs first (up to approximately 36 months)
measure: Clinical Benefit Rate, as Determined by the Investigator According to RECIST v1.1
timeFrame: From randomization until disease progression or death (up to approximately 36 months)
measure: Investigator-Assessed PFS, in Subgroups Categorized by Estrogen Receptor 1 (ESR1) Mutation Status
timeFrame: 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)
measure: Time to Deterioration (TTD) in Pain Severity
timeFrame: From Baseline until treatment discontinuation (up to approximately 36 months)
measure: 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
timeFrame: From Baseline until treatment discontinuation (up to approximately 36 months)
measure: TTD in Physical Functioning (PF)
timeFrame: From Baseline until treatment discontinuation (up to approximately 36 months)
measure: TTD in Role Functioning (RF)
timeFrame: From Baseline until treatment discontinuation (up to approximately 36 months)
measure: TTD in Global Health Status and Quality of Life (GHS/QoL)
timeFrame: From Baseline until treatment discontinuation (up to approximately 36 months)
measure: 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)
timeFrame: From Baseline until 30 days after final dose of study drug (up to approximately 36 months)
measure: Number of Participants With Vital Sign Abnormalities Over the Course of the Study
timeFrame: 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)
measure: Number of Participants With Clinical Laboratory Test Abnormalities for Hematology Parameters Over the Course of the Study
timeFrame: 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)
measure: Number of Participants With Clinical Laboratory Test Abnormalities for Biochemistry Parameters Over the Course of the Study
timeFrame: 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)
measure: Plasma Concentration of Giredestrant at Specified Timepoints
timeFrame: 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)
Other outcomes:
Locations:
city: Marietta
country: United States
facility: Northwest Georgia Oncology Centers PC - Marietta
state: Georgia
city: Cleveland
country: United States
facility: University Hospitals Seidman Cancer Center
state: Ohio
city: Tigard
country: United States
facility: Northwest Cancer Specialists - Portland (SW Barnes Rd)
state: Oregon
city: Buenos Aires
country: Argentina
facility: Fundación CENIT para la Investigación en Neurociencias
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Instituto Angel Roffo
city: Mendoza
country: Argentina
facility: Fundación Scherbovsky; General Department
city: Rosario
country: Argentina
facility: Hosp Provincial D. Centenarios; Oncology Dept
city: San Nicolás
country: Argentina
facility: Organizacion Medica de Investigacion
city: Darlinghurst
country: Australia
facility: Kinghorn Cancer Centre; St Vincents Hospital
state: New South Wales
city: St Albans
country: Australia
facility: Sunshine Hospital
state: Victoria
city: Fortaleza
country: Brazil
facility: Pronutrir - suporte nutricional e quimioterapia ltda.
state: CE
city: Ijui
country: Brazil
facility: Oncosite - Centro de Pesquisa Clinica Em Oncologia Ltda
state: RS
city: Porto Alegre
country: Brazil
facility: Santa Casa de Misericordia de Porto Alegre
state: RS
city: Sao Paulo
country: Brazil
facility: Clinica de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria Ltda
state: SP
city: Sao Paulo
country: Brazil
facility: Núcleo de Pesquisa São Camilo; ONCOLOGIA CLINICA / QUIMIOTERAPIA
state: SP
city: Changchun City
country: China
facility: The First Hospital of Jilin University
city: Guangzhou City
country: China
facility: Sun Yet-sen University Cancer Center
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
city: Linyi City
country: China
facility: Linyishi Cancer Hospital
city: Nanchang City
country: China
facility: The Third Hospital of Nanchang
city: Shanghai City
country: China
facility: Fudan University Shanghai Cancer Center
city: Tianjin
country: China
facility: Tianjin Cancer Hospital
city: Wuhan
country: China
facility: Hubei Cancer Hospital
city: Xi'an
country: China
facility: First Affiliated Hospital of Medical College of Xi'an Jiaotong University
city: Zhejiang
country: China
facility: Zhejiang Cancer Hospital
city: Aschaffenburg
country: Germany
facility: Hämato-Onkologische Schwerpunktpraxis am Klinikum Aschaffenburg
city: Berlin
country: Germany
facility: Frauenarzt-Zentrum Zehlendorf an der Teltower Eiche
city: Hamburg
country: Germany
facility: Kooperatives Mammazentrum Hamburg Krankenhaus Jerusalem
city: Paderborn
country: Germany
facility: St. Vincenz-Krankenhaus Paderborn; Haus 3 Frauenklinik
city: Stralsund
country: Germany
facility: Gynäkologie Kompetenzzentrum; Praxis Dr. med. Carsten Hielscher
city: Ashdod
country: Israel
facility: Assuta Medical Center- Ashdod; Oncology
city: Jerusalem
country: Israel
facility: Hadassah Ein Karem Hospital; Oncology Dept
city: Kfar-Saba
country: Israel
facility: Meir Medical Center; Oncology
city: Dongnam-gu, Cheonan-si
country: Korea, Republic of
facility: Soon Chun Hyang University Cheonan Hospital
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul St Mary's Hospital
city: Bialystok
country: Poland
facility: Bialostockie Centrum Onkologii; Oddzial Onkologii Klinicznej
city: Gliwice
country: Poland
facility: Narodowy Instytut Onkologii Odzia? w Gliwicach; Centrum Diagnostyki i Leczenia Chorób Piersi
city: Warszawa
country: Poland
facility: Narodowy Inst.Onkologii im.Sklodowskiej-Curie Panstw.Inst.Bad; Klinika Nowtw.Piersi i Chir.Rekonstr
city: Krasnoyarsk
country: Russian Federation
facility: Krasnoyarsk Regional Oncology Dispensary n.a. Krizhanovsky; Chemotherapy
state: Krasnodar
city: Moskva
country: Russian Federation
facility: Blokhin Cancer Research Center; Combined Treatment
state: Moskovskaja Oblast
city: Nizhny Novgorod
country: Russian Federation
facility: Filial #1 Regional Oncology Dispensary of Nizhniy Novgorod
state: Niznij Novgorod
city: Sankt-peterburg
country: Russian Federation
facility: St. Petersburg SHI "City Clinical Oncology Dispensary"
state: Sankt Petersburg
city: Kazan
country: Russian Federation
facility: Republican Clinical Oncology Dispensary of Ministry of Healthcare of Tatarstan Republic
state: Tatarstan
city: Krasnodar
country: Russian Federation
facility: Clinical Oncology Centre # 1; Chemotherapy Dept
city: Samara
country: Russian Federation
facility: Multidisciplinary clinic Reaviz
city: Sankt Petersburg
country: Russian Federation
facility: Petrov Research Inst. of Oncology
city: Volgograd
country: Russian Federation
facility: Volgograd Regional Clinical Oncology Dispensary
city: Yaroslavl
country: Russian Federation
facility: Regional Clinical Oncology Hospital
city: Singapore
country: Singapore
facility: National University Hospital; National University Cancer Institute, Singapore (NCIS)
city: Bloemfontein
country: South Africa
facility: Iatros International
city: Port Elizabeth
country: South Africa
facility: Cancercare Langenhoven Drive Oncology Centre
city: Pretoria
country: South Africa
facility: Eastleigh Breast Care Centre
city: Changhua
country: Taiwan
facility: Changhua Christian Hospital; Dept of Surgery
city: Tainan
country: Taiwan
facility: National Cheng Kung Uni Hospital; Dept of Hematology and Oncology
city: Tainan
country: Taiwan
facility: Chi-Mei Medical Centre; Hematology & Oncology
city: Taipei
country: Taiwan
facility: VETERANS GENERAL HOSPITAL; Department of General Surgery
city: Taoyuan City
country: Taiwan
facility: Chang Gung Memorial Hosipital at Linkou
city: Bangkok
country: Thailand
facility: Chulalongkorn Hospital; Medical Oncology
city: Bangkok
country: Thailand
facility: Rajavithi Hospital; Division of Medical Oncology
city: Bangkok
country: Thailand
facility: Ramathibodi Hospital; Dept of Med.-Div. of Med. Onc
city: Chang Mai
country: Thailand
facility: Maharaj Nakorn Chiang Mai Hosp; Surgery/Oncology
city: Songkhla
country: Thailand
facility: Songklanagarind Hospital; Department of Oncology
city: Ankara
country: Turkey
facility: Memorial Ankara Hastanesi
city: Ankara
country: Turkey
facility: Ankara City Hospital; Oncology
city: Antalya
country: Turkey
facility: Memorial Antalya Hospital
city: Diyarbakir
country: Turkey
facility: Dicle University Faculty of Medicine
city: Istanbul
country: Turkey
facility: Prof. Dr. Cemil Tascioglu City Hospital; Med Onc
city: Istanbul
country: Turkey
facility: Kartal Dr Lutfi Kirdar Sehir Hastanesi; Medical Oncology Department
city: Izmir
country: Turkey
facility: Katip Celebi University Ataturk Training and Research Hospital; Oncology
city: Samsun
country: Turkey
facility: Medikal Park Samsun
city: Zhytomyr
country: Ukraine
facility: Zhytomyr Regional Oncology Center
state: KIEV Governorate
city: Kyiv
country: Ukraine
facility: Kyiv City Clinical Oncological Center
city: Kyiv
country: Ukraine
facility: MI Kyiv Regional Council Kyiv Regional Oncological Dispensary; Department of Mammology
city: Sumy
country: Ukraine
facility: RCI Sumy Regional Clinical Oncological Dispensary
city: Harlow
country: United Kingdom
facility: Princess Alexandra Hospital; Oncology Department
city: London
country: United Kingdom
facility: Guys & St Thomas Hospital; Department of Oncology
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital; Oncology
city: Peterborough
country: United Kingdom
facility: Peterborough City Hospital; Oncology Research Department 018
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: