A Study Evaluating 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

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).

Study Overview

• Status: Completed
• Conditions: Early Breast Cancer
• Intervention / Treatment: Drug: Giredestrant; Drug: Palbociclib; Procedure: Surgery; Drug: Anastrozole

• Study Type: Interventional
• Enrollment (Actual): 221
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Macquarie Park, New South Wales, Australia, 2109
      • Macquarie University Hospital
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital; Medical Oncology and Pallative Care
• Brazil
  • PE
    • Recife, PE, Brazil, 50040-000
      • Hospital do Cancer de Pernambuco - HCP
  • RS
    • Porto Alegre, RS, Brazil, 90050-170
      • Santa Casa de Misericordia de Porto Alegre
  • SP
    • Sao Paulo, SP, Brazil, 01317-001
      • Clinica de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria Ltda
    • Sao Paulo, SP, Brazil, 04014-002
      • Núcleo de Pesquisa São Camilo; ONCOLOGIA CLINICA / QUIMIOTERAPIA
• Germany
  • Dresden, Germany, 01307
    • Universitätsklinikum Dresden
  • Düsseldorf, Germany, 40235
    • LUISENKRANKENHAUS; Senological Oncology
  • Erlangen, Germany, 91054
    • UNIVERSITATSKLINIKUM ERLANGEN; Department of Gynecology and Obstetrics
• Hungary
  • Kecskemet, Hungary, 6000
    • Bacs-Kiskun Megyei Korhaz, SZTE AOK Oktato Korhaza, Onkoradiologiai Kozpont; Onkoradiologiai Kozpont
  • Szekszárd, Hungary, 7100
    • Tolna Megyei Kórház, Onkológia
• Korea, Republic of
  • Gyeonggi-do, Korea, Republic of, 410-769
    • National Cancer Center; Medical Oncology
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 137-701
    • The Catholic University of Korea Seoul St. Mary'S Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 110-744
    • Severance Hospital; Internal Medicine
• Poland
  • Gdynia, Poland, 81-519
    • Szpital Morski Im. Pck; Oncology & Radiotherapy Dept
  • Lublin, Poland, 20-090
    • COZL Oddzial Onkologii Klinicznej z pododdzialem Chemioterapii Dziennej
  • Warszawa, Poland, 02-781
    • Centrum Onkologii - Inst.Im. Marii Sklodowskiej-Curie; Oncology
  • Wrocław, Poland, 53-413
    • DOLNOSLASKIE CENTRUM ONKOLOGII; Oddzial Chirurgii Piersi
• Russian Federation
  • Nizhny Novgorod, Russian Federation, 603081
    • Filial #1 Regional Oncology Dispensary of Nizhniy Novgorod
  • Saint-Petersburg, Russian Federation, 197758
    • S-Pb clinical scientific practical center of specialized kinds of medical care (oncological)
  • St. Petersburg, Russian Federation, 197758
    • FSI "SRC of Oncology n. a. N.N.Petrov of Rosmedtekhnologiy"
  • Moskovskaja Oblast
    • Moscovskaya Oblast, Moskovskaja Oblast, Russian Federation, 143423
      • Moscow City Oncology Hospital #62
  • Sankt Petersburg
    • St. Petersburg, Sankt Petersburg, Russian Federation, 195271
      • Private Healthcare Institution Clinical Hospital RZhD Medicine
  • Tatarstan
    • Kazan, Tatarstan, Russian Federation, 420029
      • Republican Clinical Oncology Dispensary of Ministry of Healthcare of Tatarstan Republic
• Spain
  • Barcelona, Spain, 08025
    • Hospital de la Santa Creu i Sant Pau
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08028
    • Hospital Universitario Quiron Dexeus
  • Granada, Spain, 18014
    • Hospital Universitario Virgen de las Nieves : Hospital General
  • Granada, Spain, 18016
    • Hospital Clínico San Cecilio
  • Lugo, Spain, 27003
    • Hospital Universitario Lucus Augusti
  • Madrid, Spain, 28040
    • Fundación Jiménez Díaz
  • Madrid, Spain, 280146
    • Hospital Universitario La Paz
  • Madrid, Spain, 28922
    • Hosp Univ Fundacion Alcorcon
  • Murcia, Spain, 30120
    • Hospital Universitario Virgen de La Arrixaca
  • Navarra, Spain, 31008
    • Hospital de Navarra; Servicio de Oncologia
  • Sevilla, Spain, 41009
    • Hospital Universitario Virgen Macarena
  • Valencia, Spain, 46014
    • Hospital General Universitario de Valencia
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Institutio Catalan De Oncologia
    • Manresa, Barcelona, Spain, 08243
      • Complejo Hospitalario de Althaia; Servicio de Oncologia
  • Cadiz
    • Jerez de La Frontera, Cadiz, Spain, 11407
      • Hospital de Jerez de la Frontera; Servicio de Oncologia
  • Lerida
    • Lleida, Lerida, Spain, 25198
      • Hospital Universitari Arnau de Vilanova
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Hospital Universitario Puerta de Hierro Majadahonda
  • Tarragona
    • Reus, Tarragona, Spain, 43204
      • Hospital Universitari Sant Joan de Reus; Planta baja, color lila
  • Tenerife
    • La Laguna, Tenerife, Spain, 38320
      • Hospital Universitario de Canarias;servicio de Oncologia
• Taiwan
  • Tainan, Taiwan, 704
    • National Cheng Kung Uni Hospital; Surgery
  • Taipei, Taiwan, 100
    • National Taiwan Uni Hospital; General Surgery
• Ukraine
  • Dnipropetrovsk, Ukraine, 49102
    • Municipal institution Dnipropetrovsk City Multifield Clinical Hospital #4; dept. of Chemotherapy
  • Kryvyi Rih, Ukraine, 50048
    • ME Kryviy Rih Oncology Dispensary of Dnipropetrovs'k Regional Council; Chemotherapy Department
  • Kyiv, Ukraine, 04107
    • Kyiv Regional Oncological Dispensary
  • Kharkiv Governorate
    • Kharkiv, Kharkiv Governorate, Ukraine, 61070
      • Regional Oncology Center of Kharkiv Regional Council; Department of Soft Tissues and Breast Cancer
    • Odesa, Kharkiv Governorate, Ukraine, 65025
      • Odesa Regional Clinical Hospital; Department of Thoracic Surgery
  • Podolia Governorate
    • Khmelnytskyi, Podolia Governorate, Ukraine, 29009
      • Khmelnytsky Regional Antitumor Center; Department of Breast, Skin, Soft Tissues and Bones Tumors
• United States
  • California
    • Burbank, California, United States, 91505
      • UCLA - Burbank
    • Laguna Hills, California, United States, 92653
      • UCLA - Laguna Hills
    • San Luis Obispo, California, United States, 93401
      • UCLA Hematology/Oncology-San Luis Obispo
    • Santa Monica, California, United States, 90404
      • UCLA Hematology Oncology-Santa Monica
    • Torrance, California, United States, 90505
      • Torrance Memorial Physician Network/Cancer Care
  • Florida
    • Orlando, Florida, United States, 32806
      • Orlando Health Inc.
    • West Palm Beach, Florida, United States, 33401
      • SCRI Florida Cancer Specialists East
  • New Jersey
    • Livingston, New Jersey, United States, 07039
      • Saint Barnabas Medical Center Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology; Sarah Cannon Research Institute
  • Wisconsin
    • Madison, Wisconsin, United States, 53762
      • Univ of Wisconsin-Madison; Clinical Science Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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
• Treatment with strong CYP3A4 inhibitors or inducers within 14 days or 5 drug elimination half-lives prior to randomization
• Known HIV infection
• Serious infection requiring oral or IV antibiotics, or other clinically significant infection within 14 days prior to screening
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Giredestrant + Palbociclib	Drug: Giredestrant; 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.; Other Names: GDC-9545; RO7197597; RG6171; Drug: 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.; Procedure: Surgery; 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.
Active Comparator: Anastrozole + Palbociclib	Drug: 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.; Procedure: Surgery; 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.; Drug: Anastrozole; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in Ki67 Scores from Baseline to Week 2	Baseline and Week 2

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall Response Rate by Ultrasound, Defined as the Percentage of Participants with a Complete Response (CR) or Partial Response (PR), as Determined by the Investigator According to Modified Response Evaluation Criteria in Solid Tumors (mRECIST)	Baseline and Cycle 4 Day 1 (1 cycle is 28 days)
Complete Cell Cycle Arrest Rate, Defined as the Percentage of Participants with Centrally Assessed Ki67 Scores ≤2.7% Stained Nuclei Upon Treatment at Week 2	Week 2
Incidence and Severity of Adverse Events, with Severity Determined in Accordance to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)	From Baseline until 28 days after final dose of study treatment (up to 24 weeks)
Change from Baseline in Respiratory Rate Over Time	From Baseline until 28 days after final dose of study treatment (up to 24 weeks)
Change from Baseline in Pulse Rate Over Time	From Baseline until 28 days after final dose of study treatment (up to 24 weeks)
Change from Baseline in Systolic Blood Pressure Over Time	From Baseline until 28 days after final dose of study treatment (up to 24 weeks)
Change from Baseline in Diastolic Blood Pressure Over Time	From Baseline until 28 days after final dose of study treatment (up to 24 weeks)
Change from Baseline in Body Temperature Over Time	From Baseline until 28 days after final dose of study treatment (up to 24 weeks)
Number of Participants with Clinical Laboratory Abnormalities in Hematology Test Parameters	From Baseline until 28 days after final dose of study treatment (up to 24 weeks)
Number of Participants with Clinical Laboratory Abnormalities in Blood Chemistry Test Parameters	From Baseline until 28 days after final dose of study treatment (up to 24 weeks)
Plasma Concentration of Giredestrant at Specified Timepoints	Cycle 0 Days 1 and 15, Cycle 2 Day 1 (1 cycle is 28 days), and End of Study Visit (up to 24 weeks)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): September 4, 2020
• Primary Completion (Actual): July 6, 2021
• Study Completion (Actual): November 24, 2021

Study Registration Dates

• First Submitted: June 16, 2020
• First Submitted That Met QC Criteria: June 16, 2020
• First Posted (Actual): June 18, 2020

Study Record Updates

• Last Update Posted (Actual): June 27, 2022
• Last Update Submitted That Met QC Criteria: June 23, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protein Kinase Inhibitors; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Palbociclib; Anastrozole
• Other Study ID Numbers: WO42133; 2020-001007-16 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

IPD Plan Description

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).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No