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)

NCT ID: NCT04436744

Last Updated: 2023-02-02

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

221 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-09-04

Study Completion Date

2021-11-24

Brief Summary

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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).

Detailed Description

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Conditions

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Early Breast Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Giredestrant + Palbociclib

Group Type EXPERIMENTAL

Giredestrant

Intervention Type DRUG

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.

Palbociclib

Intervention Type DRUG

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

Intervention Type PROCEDURE

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.

Anastrozole + Palbociclib

Group Type ACTIVE_COMPARATOR

Anastrozole

Intervention Type DRUG

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.

Palbociclib

Intervention Type DRUG

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

Intervention Type PROCEDURE

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.

Interventions

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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.

Intervention Type 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.

Intervention Type 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.

Intervention Type DRUG

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.

Intervention Type PROCEDURE

Other Intervention Names

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GDC-9545 RO7197597 RG6171

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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UCLA - Burbank

Burbank, California, United States

Site Status

UCLA - Laguna Hills

Laguna Hills, California, United States

Site Status

UCLA Hematology/Oncology-San Luis Obispo

San Luis Obispo, California, United States

Site Status

UCLA Hematology Oncology-Santa Monica

Santa Monica, California, United States

Site Status

Torrance Memorial Physician Network/Cancer Care

Torrance, California, United States

Site Status

Orlando Health Inc.

Orlando, Florida, United States

Site Status

SCRI Florida Cancer Specialists East

West Palm Beach, Florida, United States

Site Status

Saint Barnabas Medical Center Cancer Center

Livingston, New Jersey, United States

Site Status

Tennessee Oncology; Sarah Cannon Research Institute

Nashville, Tennessee, United States

Site Status

Univ of Wisconsin-Madison; Clinical Science Center

Madison, Wisconsin, United States

Site Status

Macquarie University Hospital

Macquarie Park, New South Wales, Australia

Site Status

Westmead Hospital; Medical Oncology and Pallative Care

Westmead, New South Wales, Australia

Site Status

Hospital do Cancer de Pernambuco - HCP

Recife, Pernambuco, Brazil

Site Status

Santa Casa de Misericordia de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Site Status

Clinica de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria Ltda

São Paulo, São Paulo, Brazil

Site Status

Núcleo de Pesquisa São Camilo; ONCOLOGIA CLINICA / QUIMIOTERAPIA

São Paulo, São Paulo, Brazil

Site Status

Universitätsklinikum Dresden

Dresden, , Germany

Site Status

LUISENKRANKENHAUS; Senological Oncology

Düsseldorf, , Germany

Site Status

UNIVERSITATSKLINIKUM ERLANGEN; Department of Gynecology and Obstetrics

Erlangen, , Germany

Site Status

Bacs-Kiskun Megyei Korhaz, SZTE AOK Oktato Korhaza, Onkoradiologiai Kozpont; Onkoradiologiai Kozpont

Kecskemét, , Hungary

Site Status

Tolna Megyei Kórház, Onkológia

Szekszárd, , Hungary

Site Status

Szpital Morski Im. Pck; Oncology & Radiotherapy Dept

Gdynia, , Poland

Site Status

COZL Oddzial Onkologii Klinicznej z pododdzialem Chemioterapii Dziennej

Lublin, , Poland

Site Status

Centrum Onkologii - Inst.Im. Marii Sklodowskiej-Curie; Oncology

Warsaw, , Poland

Site Status

DOLNOSLASKIE CENTRUM ONKOLOGII; Oddzial Chirurgii Piersi

Wroclaw, , Poland

Site Status

Moscow City Oncology Hospital #62

Moscovskaya Oblast, Moscow Oblast, Russia

Site Status

Private Healthcare Institution Clinical Hospital RZhD Medicine

Saint Petersburg, Sankt-Peterburg, Russia

Site Status

Republican Clinical Oncology Dispensary of Ministry of Healthcare of Tatarstan Republic

Kazan', Tatarstan Republic, Russia

Site Status

Filial #1 Regional Oncology Dispensary of Nizhniy Novgorod

Nizhny Novgorod, , Russia

Site Status

FSI "SRC of Oncology n. a. N.N.Petrov of Rosmedtekhnologiy"

Saint Petersburg, , Russia

Site Status

S-Pb clinical scientific practical center of specialized kinds of medical care (oncological)

Saint Petersburg, , Russia

Site Status

National Cancer Center; Medical Oncology

Gyeonggi-do, , South Korea

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Asan Medical Center

Seoul, , South Korea

Site Status

Severance Hospital; Internal Medicine

Seoul, , South Korea

Site Status

Samsung Medical Center

Seoul, , South Korea

Site Status

The Catholic University of Korea Seoul St. Mary's Hospital

Seoul, , South Korea

Site Status

Institutio Catalan De Oncologia

Badalona, Barcelona, Spain

Site Status

Complejo Hospitalario de Althaia; Servicio de Oncologia

Manresa, Barcelona, Spain

Site Status

Hospital de Jerez de la Frontera; Servicio de Oncologia

Jerez de la Frontera, Cadiz, Spain

Site Status

Hospital Universitari Arnau de Vilanova

Lleida, Lerida, Spain

Site Status

Hospital Universitario Puerta de Hierro Majadahonda

Majadahonda, Madrid, Spain

Site Status

Hospital de Navarra; Servicio de Oncologia

Navarra, Navarre, Spain

Site Status

Hospital Universitari Sant Joan de Reus; Planta baja, color lila

Reus, Tarragona, Spain

Site Status

Hospital Universitario de Canarias;servicio de Oncologia

San Cristóbal de La Laguna, Tenerife, Spain

Site Status

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Site Status

Hospital Universitario Quirón Dexeus

Barcelona, , Spain

Site Status

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Site Status

Hospital Universitario Virgen de las Nieves : Hospital General

Granada, , Spain

Site Status

Hospital Clinico San Cecilio

Granada, , Spain

Site Status

Hospital Universitario Lucus Augusti

Lugo, , Spain

Site Status

Hospital Universitario La Paz

Madrid, , Spain

Site Status

Fundación Jimenez Díaz

Madrid, , Spain

Site Status

Hosp Univ Fundacion Alcorcon

Madrid, , Spain

Site Status

Hospital Universitario Virgen de La Arrixaca

Murcia, , Spain

Site Status

Hospital Universitario Virgen Macarena

Seville, , Spain

Site Status

Hospital General Universitario de Valencia

Valencia, , Spain

Site Status

National Cheng Kung Uni Hospital; Surgery

Tainan City, , Taiwan

Site Status

National Taiwan Uni Hospital; General Surgery

Taipei, , Taiwan

Site Status

Regional Oncology Center of Kharkiv Regional Council; Department of Soft Tissues and Breast Cancer

Kharkiv, Kharkiv Governorate, Ukraine

Site Status

Odesa Regional Clinical Hospital; Department of Thoracic Surgery

Odesa, Kharkiv Governorate, Ukraine

Site Status

Khmelnytsky Regional Antitumor Center; Department of Breast, Skin, Soft Tissues and Bones Tumors

Khmelnytskyi, Podolia Governorate, Ukraine

Site Status

Municipal institution Dnipropetrovsk City Multifield Clinical Hospital #4; dept. of Chemotherapy

Dnipropetrovsk, , Ukraine

Site Status

ME Kryviy Rih Oncology Dispensary of Dnipropetrovs'k Regional Council; Chemotherapy Department

Kryvyi Rih, , Ukraine

Site Status

Kyiv Regional Oncological Dispensary

Kyiv, , Ukraine

Site Status

Countries

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United States Australia Brazil Germany Hungary Poland Russia South Korea Spain Taiwan Ukraine

References

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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.

Reference Type DERIVED
PMID: 37657462 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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2020-001007-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

WO42133

Identifier Type: -

Identifier Source: org_study_id

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