Clinical trial NCT04436744: 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)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Early Breast Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2020-06-18
Enrollment: 221
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

Primary outcomes:
measure: Relative Percent Change in Ki67 Scores From Baseline to Week 2
timeFrame: Baseline, Week 2
Secondary outcomes:
measure: Overall Response Rate (ORR) by Ultrasound as Determined by the Investigator
timeFrame: Baseline up to Cycle 4 Day 1 (each cycle is 28 days)
measure: Complete Cell Cycle Arrest (CCCA) Rate at Week 2
timeFrame: Week 2
measure: 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)
timeFrame: From baseline up to 28 days after the last dose (up to approximately 24 weeks)
measure: Change From Baseline in Respiratory Rate Over Time
timeFrame: 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)
measure: Change From Baseline in Pulse Rate Over Time
timeFrame: 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)
measure: Change From Baseline in Systolic Blood Pressure Over Time
timeFrame: 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)
measure: Change From Baseline in Diastolic Blood Pressure Over Time
timeFrame: 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)
measure: Change From Baseline in Body Temperature Over Time
timeFrame: 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)
measure: Number of Participants With Shifts in Hematology Test Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline
timeFrame: From baseline up to 28 days after the last dose (up to approximately 24 weeks)
measure: Number of Participants With Shifts in Blood Chemistry Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline
timeFrame: From baseline up to 28 days after the last dose (up to approximately 24 weeks)
measure: Plasma Concentration of Giredestrant at Specified Timepoints
timeFrame: Window of Opportunity Phase: Day 1 (3 hours Postdose) and Day 15 (Predose) during Cycle 0 (the 15-day period in Window of Opportunity Phase is called Cycle 0 for PK analysis); Neoadjuvant Phase: Cycle 2 Day 1, Predose
Other outcomes:
Locations:
city: Burbank
country: United States
facility: UCLA - Burbank
state: California
city: Laguna Hills
country: United States
facility: UCLA - Laguna Hills
state: California
city: San Luis Obispo
country: United States
facility: UCLA Hematology/Oncology-San Luis Obispo
state: California
city: Santa Monica
country: United States
facility: UCLA Hematology Oncology-Santa Monica
state: California
city: Torrance
country: United States
facility: Torrance Memorial Physician Network/Cancer Care
state: California
city: Orlando
country: United States
facility: Orlando Health Inc.
state: Florida
city: West Palm Beach
country: United States
facility: SCRI Florida Cancer Specialists East
state: Florida
city: Livingston
country: United States
facility: Saint Barnabas Medical Center Cancer Center
state: New Jersey
city: Nashville
country: United States
facility: Tennessee Oncology; Sarah Cannon Research Institute
state: Tennessee
city: Madison
country: United States
facility: Univ of Wisconsin-Madison; Clinical Science Center
state: Wisconsin
city: Macquarie Park
country: Australia
facility: Macquarie University Hospital
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital; Medical Oncology and Pallative Care
state: New South Wales
city: Recife
country: Brazil
facility: Hospital do Cancer de Pernambuco - HCP
state: PE
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: Dresden
country: Germany
facility: Universitätsklinikum Dresden
city: Düsseldorf
country: Germany
facility: LUISENKRANKENHAUS; Senological Oncology
city: Erlangen
country: Germany
facility: UNIVERSITATSKLINIKUM ERLANGEN; Department of Gynecology and Obstetrics
city: Kecskemet
country: Hungary
facility: Bacs-Kiskun Megyei Korhaz, SZTE AOK Oktato Korhaza, Onkoradiologiai Kozpont; Onkoradiologiai Kozpont
city: Szekszárd
country: Hungary
facility: Tolna Megyei Kórház, Onkológia
city: Gyeonggi-do
country: Korea, Republic of
facility: National Cancer Center; Medical Oncology
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Severance Hospital; Internal Medicine
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea Seoul St. Mary's Hospital
city: Gdynia
country: Poland
facility: Szpital Morski Im. Pck; Oncology & Radiotherapy Dept
city: Lublin
country: Poland
facility: COZL Oddzial Onkologii Klinicznej z pododdzialem Chemioterapii Dziennej
city: Warszawa
country: Poland
facility: Centrum Onkologii - Inst.Im. Marii Sklodowskiej-Curie; Oncology
city: Wrocław
country: Poland
facility: DOLNOSLASKIE CENTRUM ONKOLOGII; Oddzial Chirurgii Piersi
city: Moscovskaya Oblast
country: Russian Federation
facility: Moscow City Oncology Hospital #62
state: Moskovskaja Oblast
city: St. Petersburg
country: Russian Federation
facility: Private Healthcare Institution Clinical Hospital RZhD Medicine
state: Sankt Petersburg
city: Kazan
country: Russian Federation
facility: Republican Clinical Oncology Dispensary of Ministry of Healthcare of Tatarstan Republic
state: Tatarstan
city: Nizhny Novgorod
country: Russian Federation
facility: Filial #1 Regional Oncology Dispensary of Nizhniy Novgorod
city: Saint-Petersburg
country: Russian Federation
facility: S-Pb clinical scientific practical center of specialized kinds of medical care (oncological)
city: St. Petersburg
country: Russian Federation
facility: FSI "SRC of Oncology n. a. N.N.Petrov of Rosmedtekhnologiy"
city: Badalona
country: Spain
facility: Institutio Catalan De Oncologia
state: Barcelona
city: Manresa
country: Spain
facility: Complejo Hospitalario de Althaia; Servicio de Oncologia
state: Barcelona
city: Jerez de La Frontera
country: Spain
facility: Hospital de Jerez de la Frontera; Servicio de Oncologia
state: Cadiz
city: Lleida
country: Spain
facility: Hospital Universitari Arnau de Vilanova
state: Lerida
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro Majadahonda
state: Madrid
city: Reus
country: Spain
facility: Hospital Universitari Sant Joan de Reus; Planta baja, color lila
state: Tarragona
city: La Laguna
country: Spain
facility: Hospital Universitario de Canarias;servicio de Oncologia
state: Tenerife
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Universitario Quirón Dexeus
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Granada
country: Spain
facility: Hospital Universitario Virgen de las Nieves : Hospital General
city: Granada
country: Spain
facility: Hospital Clinico San Cecilio
city: Lugo
country: Spain
facility: Hospital Universitario Lucus Augusti
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Fundación Jimenez Díaz
city: Madrid
country: Spain
facility: Hosp Univ Fundacion Alcorcon
city: Murcia
country: Spain
facility: Hospital Universitario Virgen de La Arrixaca
city: Navarra
country: Spain
facility: Hospital de Navarra; Servicio de Oncologia
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia
city: Tainan
country: Taiwan
facility: National Cheng Kung Uni Hospital; Surgery
city: Taipei
country: Taiwan
facility: National Taiwan Uni Hospital; General Surgery
city: Kharkiv
country: Ukraine
facility: Regional Oncology Center of Kharkiv Regional Council; Department of Soft Tissues and Breast Cancer
state: Kharkiv Governorate
city: Odesa
country: Ukraine
facility: Odesa Regional Clinical Hospital; Department of Thoracic Surgery
state: Kharkiv Governorate
city: Khmelnytskyi
country: Ukraine
facility: Khmelnytsky Regional Antitumor Center; Department of Breast, Skin, Soft Tissues and Bones Tumors
state: Podolia Governorate
city: Dnipropetrovsk
country: Ukraine
facility: Municipal institution Dnipropetrovsk City Multifield Clinical Hospital #4; dept. of Chemotherapy
city: Kryvyi Rih
country: Ukraine
facility: ME Kryviy Rih Oncology Dispensary of Dnipropetrovs'k Regional Council; Chemotherapy Department
city: Kyiv
country: Ukraine
facility: Kyiv Regional Oncological Dispensary
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: