A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Giredestrant Plus Palbociclib Compared With Anastrozole Plus Palbociclib for Postmenopausal Women With Estrogen Receptor-Positive and HER2-Negative Untreated Early Breast Cancer (coopERA Breast Cancer)
A Randomized, Multicenter, Open-Label, Two-Arm, Phase II, Neoadjuvant Study Evaluating the Efficacy, Safety, and Pharmacokinetics of GDC-9545 Plus Palbociclib Compared With Anastrozole Plus Palbociclib for Postmenopausal Women With Estrogen Receptor-Positive and HER2-Negative Untreated Early Breast Cancer
2 other identifiers
interventional
221
11 countries
65
Brief Summary
This is a randomized, multicenter, open-label, two-arm, Phase II study to evaluate the efficacy, safety, and pharmacokinetics of giredestrant versus anastrozole (in the window-of-opportunity phase) and giredestrant plus palbociclib compared with anastrozole plus palbociclib (in the neoadjuvant phase) in postmenopausal women with untreated, estrogen receptor (ER)-positive, human epidermal growth factor receptor-2 (HER2)-negative, early breast cancer. The study consists of a screening period of up to 28 days, a window-of-opportunity phase for 14 days, followed by a neoadjuvant treatment phase for 16 weeks (four 28-day cycles), surgery, and an end of study visit (28 days after the final dose of study treatment).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Sep 2020
Shorter than P25 for phase_2
65 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 16, 2020
CompletedFirst Posted
Study publicly available on registry
June 18, 2020
CompletedStudy Start
First participant enrolled
September 4, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 6, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
November 24, 2021
CompletedResults Posted
Study results publicly available
February 2, 2023
CompletedFebruary 2, 2023
January 1, 2023
10 months
June 16, 2020
November 21, 2022
January 9, 2023
Conditions
Outcome Measures
Primary Outcomes (1)
Relative Percent Change in Ki67 Scores From Baseline to Week 2
Ki67 is a proliferation biomarker with prognostic value in ER-positive breast cancer. Ki67 scores were centrally assessed with immunohistochemistry and defined as a percentage of positively stained tumor cell nuclei among the total number of tumor cells assessed, with a potential range of 0-100%. A score of 0% indicates no tumor cell nuclei with Ki67 staining and a score of 100% indicates all tumor cell nuclei are positively stained with Ki67. The relative percentage change was calculated using Ki67 scores at Baseline and Week 2. Relative Percent Change was defined as Week 2 Ki67 percentage score/Baseline Ki67 percentage score\*100. A smaller value of relative percentage change indicates improvement.
Baseline, Week 2
Secondary Outcomes (11)
Overall Response Rate (ORR) by Ultrasound as Determined by the Investigator
Baseline up to Cycle 4 Day 1 (each cycle is 28 days)
Complete Cell Cycle Arrest (CCCA) Rate at Week 2
Week 2
Number of Participants With Adverse Events (AEs) With Severity Determined in Accordance With National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)
From baseline up to 28 days after the last dose (up to approximately 24 weeks)
Change From Baseline in Respiratory Rate Over Time
Baseline; Cycles 1-2: Day 1 and Day 15; Cycles 3-4: Day 1; day of surgery (up to 2 weeks after the final dose of study treatment [approximately Week 18]) and end of study (up to approximately 24 weeks)
Change From Baseline in Pulse Rate Over Time
Baseline; Cycles 1-2: Day 1 and Day 15; Cycles 3-4: Day 1; day of surgery (up to 2 weeks after the final dose of study treatment [approximately Week 18]) and end of study (up to approximately 24 weeks)
- +6 more secondary outcomes
Study Arms (2)
Giredestrant + Palbociclib
EXPERIMENTALAnastrozole + Palbociclib
ACTIVE COMPARATORInterventions
During the window-of-opportunity phase (first 2 weeks) giredestrant will be taken orally once per day (QD) as a single agent. During the neoadjuvant treatment phase, giredestrant will be taken orally QD on Days 1-28 of each 28-day cycle for a total of 4 cycles, in combination with palbociclib.
During the window-of-opportunity phase (first 2 weeks), anastrozole 1 mg will be taken orally QD as a single agent. During the neoadjuvant treatment phase, anastrozole 1 mg will be taken orally QD on Days 1-28 of each 28-day cycle for a total of 4 cycles, in combination with palbociclib.
During the neoadjuvant treatment phase, palbociclib 125 mg will be taken orally QD on Days 1-21 of a 28-day cycle for a total of 4 cycles.
Surgery must be performed within a maximum of 14 days after the final cycle in the neoadjuvant treatment phase and ideally should occur as soon as possible after the last dose of study treatment.
Eligibility Criteria
You may qualify if:
- Postmenopausal women age ≥18 years
- Histologically confirmed operable or inoperable invasive breast carcinoma
- Candidate for neoadjuvant treatment and considered appropriate for endocrine therapy
- Willingness to undergo breast surgery after neoadjuvant treatment and to provide three mandatory tumor samples
- Documented estrogen receptor (ER)-positive tumor in accordance to American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines (Allison et al.2020), assessed locally and defined as ≥1% of tumor cells stained positive on the basis of the most recent tumor biopsy
- Documented progesterone receptor status (positive or negative) as per local assessment
- Documented human epidermal growth factor receptor-2 (HER2)-negative tumor in accordance to 2018 ASCO/CAP guidelines (Wolff et al. 2018), assessed locally on the most recent tumor biopsy
- Ki67 score ≥5% analyzed centrally or locally
- Eastern Cooperative Oncology Group Performance Status 0-1
- Adequate organ function
You may not qualify if:
- Stage IV (metastatic) breast cancer
- Inflammatory breast cancer (cT4d)
- Bilateral invasive breast cancer
- History of invasive breast cancer, ductal carcinoma in situ or lobular carcinoma in situ and other malignancy within 5 years prior to screening
- Previous systemic or local treatment for the primary breast cancer currently under investigation
- History of any prior treatment with aromatase inhibitors (AIs), tamoxifen, selective estrogen receptor down regulator, or cyclin-dependent kinase 4 and 6 inhibitors
- Major surgery within 4 weeks prior to randomization
- Known clinically significant history of liver disease consistent with Child-Pugh Class B or C, including hepatitis
- Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study
- History of allergy to anastrozole, or palbociclib or any of its excipients
- Known issues with swallowing oral medication
- History of documented hemorrhagic diathesis, coagulopathy, or thromboembolism
- Active cardiac disease or history of cardiac dysfunction
- Current treatment with medications that are well known to prolong the QT interval
- Active inflammatory bowel disease or chronic diarrhea, short bowel syndrome, or major upper gastrointestinal surgery including gastric resection
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (65)
UCLA - Burbank
Burbank, California, 91505, United States
UCLA - Laguna Hills
Laguna Hills, California, 92653, United States
UCLA Hematology/Oncology-San Luis Obispo
San Luis Obispo, California, 93401, United States
UCLA Hematology Oncology-Santa Monica
Santa Monica, California, 90404, United States
Torrance Memorial Physician Network/Cancer Care
Torrance, California, 90505, United States
Orlando Health Inc.
Orlando, Florida, 32806, United States
SCRI Florida Cancer Specialists East
West Palm Beach, Florida, 33401, United States
Saint Barnabas Medical Center Cancer Center
Livingston, New Jersey, 07039, United States
Tennessee Oncology; Sarah Cannon Research Institute
Nashville, Tennessee, 37203, United States
Univ of Wisconsin-Madison; Clinical Science Center
Madison, Wisconsin, 53762, United States
Macquarie University Hospital
Macquarie Park, New South Wales, 2109, Australia
Westmead Hospital; Medical Oncology and Pallative Care
Westmead, New South Wales, 2145, Australia
Hospital do Cancer de Pernambuco - HCP
Recife, Pernambuco, 50040-000, Brazil
Santa Casa de Misericordia de Porto Alegre
Porto Alegre, Rio Grande do Sul, 90050-170, Brazil
Clinica de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria Ltda
São Paulo, São Paulo, 01317-001, Brazil
Núcleo de Pesquisa São Camilo; ONCOLOGIA CLINICA / QUIMIOTERAPIA
São Paulo, São Paulo, 04014-002, Brazil
Universitätsklinikum Dresden
Dresden, 01307, Germany
LUISENKRANKENHAUS; Senological Oncology
Düsseldorf, 40235, Germany
UNIVERSITATSKLINIKUM ERLANGEN; Department of Gynecology and Obstetrics
Erlangen, 91054, Germany
Bacs-Kiskun Megyei Korhaz, SZTE AOK Oktato Korhaza, Onkoradiologiai Kozpont; Onkoradiologiai Kozpont
Kecskemét, 6000, Hungary
Tolna Megyei Kórház, Onkológia
Szekszárd, 7100, Hungary
Szpital Morski Im. Pck; Oncology & Radiotherapy Dept
Gdynia, 81-519, Poland
COZL Oddzial Onkologii Klinicznej z pododdzialem Chemioterapii Dziennej
Lublin, 20-090, Poland
Centrum Onkologii - Inst.Im. Marii Sklodowskiej-Curie; Oncology
Warsaw, 02-781, Poland
DOLNOSLASKIE CENTRUM ONKOLOGII; Oddzial Chirurgii Piersi
Wroclaw, 53-413, Poland
Moscow City Oncology Hospital #62
Moscovskaya Oblast, Moscow Oblast, 143423, Russia
Private Healthcare Institution Clinical Hospital RZhD Medicine
Saint Petersburg, Sankt-Peterburg, 195271, Russia
Republican Clinical Oncology Dispensary of Ministry of Healthcare of Tatarstan Republic
Kazan', Tatarstan Republic, 420029, Russia
Filial #1 Regional Oncology Dispensary of Nizhniy Novgorod
Nizhny Novgorod, 603081, Russia
FSI "SRC of Oncology n. a. N.N.Petrov of Rosmedtekhnologiy"
Saint Petersburg, 197758, Russia
S-Pb clinical scientific practical center of specialized kinds of medical care (oncological)
Saint Petersburg, 197758, Russia
National Cancer Center; Medical Oncology
Gyeonggi-do, 410-769, South Korea
Seoul National University Hospital
Seoul, 03080, South Korea
Asan Medical Center
Seoul, 05505, South Korea
Severance Hospital; Internal Medicine
Seoul, 110-744, South Korea
Samsung Medical Center
Seoul, 135-710, South Korea
The Catholic University of Korea Seoul St. Mary's Hospital
Seoul, 6591, South Korea
Institutio Catalan De Oncologia
Badalona, Barcelona, 08916, Spain
Complejo Hospitalario de Althaia; Servicio de Oncologia
Manresa, Barcelona, 08243, Spain
Hospital de Jerez de la Frontera; Servicio de Oncologia
Jerez de la Frontera, Cadiz, 11407, Spain
Hospital Universitari Arnau de Vilanova
Lleida, Lerida, 25198, Spain
Hospital Universitario Puerta de Hierro Majadahonda
Majadahonda, Madrid, 28222, Spain
Hospital de Navarra; Servicio de Oncologia
Navarra, Navarre, 31008, Spain
Hospital Universitari Sant Joan de Reus; Planta baja, color lila
Reus, Tarragona, 43204, Spain
Hospital Universitario de Canarias;servicio de Oncologia
San Cristóbal de La Laguna, Tenerife, 38320, Spain
Hospital de la Santa Creu i Sant Pau
Barcelona, 08025, Spain
Hospital Universitario Quirón Dexeus
Barcelona, 08028, Spain
Hospital Universitari Vall d'Hebron
Barcelona, 08035, Spain
Hospital Universitario Virgen de las Nieves : Hospital General
Granada, 18014, Spain
Hospital Clinico San Cecilio
Granada, 18016, Spain
Hospital Universitario Lucus Augusti
Lugo, 27003, Spain
Hospital Universitario La Paz
Madrid, 280146, Spain
Fundación Jimenez Díaz
Madrid, 28040, Spain
Hosp Univ Fundacion Alcorcon
Madrid, 28922, Spain
Hospital Universitario Virgen de La Arrixaca
Murcia, 30120, Spain
Hospital Universitario Virgen Macarena
Seville, 41009, Spain
Hospital General Universitario de Valencia
Valencia, 46014, Spain
National Cheng Kung Uni Hospital; Surgery
Tainan, 704, Taiwan
National Taiwan Uni Hospital; General Surgery
Taipei, 100, Taiwan
Regional Oncology Center of Kharkiv Regional Council; Department of Soft Tissues and Breast Cancer
Kharkiv, Kharkiv Governorate, 61070, Ukraine
Odesa Regional Clinical Hospital; Department of Thoracic Surgery
Odesa, Kharkiv Governorate, 65025, Ukraine
Khmelnytsky Regional Antitumor Center; Department of Breast, Skin, Soft Tissues and Bones Tumors
Khmelnytskyi, Podolia Governorate, 29009, Ukraine
Municipal institution Dnipropetrovsk City Multifield Clinical Hospital #4; dept. of Chemotherapy
Dnipropetrovsk, 49102, Ukraine
ME Kryviy Rih Oncology Dispensary of Dnipropetrovs'k Regional Council; Chemotherapy Department
Kryvyi Rih, 50048, Ukraine
Kyiv Regional Oncological Dispensary
Kyiv, 04107, Ukraine
Related Publications (1)
Hurvitz SA, Bardia A, Quiroga V, Park YH, Blancas I, Alonso-Romero JL, Vasiliev A, Adamchuk H, Salgado M, Yardley DA, Berzoy O, Zamora-Aunon P, Chan D, Spera G, Xue C, Ferreira E, Badovinac Crnjevic T, Perez-Moreno PD, Lopez-Valverde V, Steinseifer J, Fernando TM, Moore HM, Fasching PA; coopERA Breast Cancer study group. Neoadjuvant palbociclib plus either giredestrant or anastrozole in oestrogen receptor-positive, HER2-negative, early breast cancer (coopERA Breast Cancer): an open-label, randomised, controlled, phase 2 study. Lancet Oncol. 2023 Sep;24(9):1029-1041. doi: 10.1016/S1470-2045(23)00268-1.
PMID: 37657462DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Communications
- Organization
- Hoffmann-La Roche
Study Officials
- STUDY DIRECTOR
Clinical Trials
Hoffmann-La Roche
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 16, 2020
First Posted
June 18, 2020
Study Start
September 4, 2020
Primary Completion
July 6, 2021
Study Completion
November 24, 2021
Last Updated
February 2, 2023
Results First Posted
February 2, 2023
Record last verified: 2023-01
Data Sharing
- IPD Sharing
- Will share
Qualified researchers may request access to individual patient level data through the request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on Sharing of Clinical Study Information and how to request access to related clinical study documents, see here (https://www.roche.com/research\_and\_development/who\_we\_are\_how\_we\_work/clinical\_trials/our\_commitment\_to\_data\_sharing.htm).