Early Breast CancerPhase 2NCT04436744
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 Phase 2 study testing Giredestrant, Anastrozole and Palbociclib in people with Early Breast Cancer, run by Hoffmann-La Roche at 65 sites in 11 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Early Breast Cancer
- What is being tested?
- Giredestrant, Anastrozole and Palbociclib
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 221 participants
- Where
- 65 sitesin 11 countries
- Study dates
- 4 Sep 2020to 24 Nov 2021
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
65 sites in 11 countries.
65 sites in 11 countries
Spain20 sites
Institutio Catalan De Oncologia
Badalona, Barcelona, 08916
Hospital de la Santa Creu i Sant Pau
Barcelona, 08025
Hospital Universitario Quirón Dexeus
Barcelona, 08028
Hospital Universitari Vall d'Hebron
Barcelona, 08035
Hospital Universitario Virgen de las Nieves : Hospital General
Granada, 18014
Hospital Clinico San Cecilio
Granada, 18016
Hospital de Jerez de la Frontera; Servicio de Oncologia
Jerez de la Frontera, Cadiz, 11407
Hospital Universitari Arnau de Vilanova
Lleida, Lerida, 25198
Hospital Universitario Lucus Augusti
Lugo, 27003
Hospital Universitario La Paz
Madrid, 280146
Fundación Jimenez Díaz
Madrid, 28040
Hosp Univ Fundacion Alcorcon
Madrid, 28922
Hospital Universitario Puerta de Hierro Majadahonda
Majadahonda, Madrid, 28222
Complejo Hospitalario de Althaia; Servicio de Oncologia
Manresa, Barcelona, 08243
Hospital Universitario Virgen de La Arrixaca
Murcia, 30120
Hospital de Navarra; Servicio de Oncologia
Navarra, Navarre, 31008
Hospital Universitari Sant Joan de Reus; Planta baja, color lila
Reus, Tarragona, 43204
Hospital Universitario de Canarias;servicio de Oncologia
San Cristóbal de La Laguna, Tenerife, 38320
Hospital Universitario Virgen Macarena
Seville, 41009
Hospital General Universitario de Valencia
Valencia, 46014
United States10 sites
UCLA - Burbank
Burbank, California, 91505
UCLA - Laguna Hills
Laguna Hills, California, 92653
Saint Barnabas Medical Center Cancer Center
Livingston, New Jersey, 07039
Univ of Wisconsin-Madison; Clinical Science Center
Madison, Wisconsin, 53762
Tennessee Oncology; Sarah Cannon Research Institute
Nashville, Tennessee, 37203
Orlando Health Inc.
Orlando, Florida, 32806
UCLA Hematology/Oncology-San Luis Obispo
San Luis Obispo, California, 93401
UCLA Hematology Oncology-Santa Monica
Santa Monica, California, 90404
Torrance Memorial Physician Network/Cancer Care
Torrance, California, 90505
SCRI Florida Cancer Specialists East
West Palm Beach, Florida, 33401
Russia6 sites
Republican Clinical Oncology Dispensary of Ministry of Healthcare of Tatarstan Republic
Kazan', Tatarstan Republic, 420029
Moscow City Oncology Hospital #62
Moscovskaya Oblast, Moscow Oblast, 143423
Filial #1 Regional Oncology Dispensary of Nizhniy Novgorod
Nizhny Novgorod, 603081
Private Healthcare Institution Clinical Hospital RZhD Medicine
Saint Petersburg, Sankt-Peterburg, 195271
FSI "SRC of Oncology n. a. N.N.Petrov of Rosmedtekhnologiy"
Saint Petersburg, 197758
S-Pb clinical scientific practical center of specialized kinds of medical care (oncological)
Saint Petersburg, 197758
South Korea6 sites
National Cancer Center; Medical Oncology
Gyeonggi-do, 410-769
Seoul National University Hospital
Seoul, 03080
Asan Medical Center
Seoul, 05505
Severance Hospital; Internal Medicine
Seoul, 110-744
Samsung Medical Center
Seoul, 135-710
The Catholic University of Korea Seoul St. Mary's Hospital
Seoul, 6591
Ukraine6 sites
Municipal institution Dnipropetrovsk City Multifield Clinical Hospital #4; dept. of Chemotherapy
Dnipropetrovsk, 49102
Regional Oncology Center of Kharkiv Regional Council; Department of Soft Tissues and Breast Cancer
Kharkiv, Kharkiv Governorate, 61070
Khmelnytsky Regional Antitumor Center; Department of Breast, Skin, Soft Tissues and Bones Tumors
Khmelnytskyi, Podolia Governorate, 29009
ME Kryviy Rih Oncology Dispensary of Dnipropetrovs'k Regional Council; Chemotherapy Department
Kryvyi Rih, 50048
Kyiv Regional Oncological Dispensary
Kyiv, 04107
Odesa Regional Clinical Hospital; Department of Thoracic Surgery
Odesa, Kharkiv Governorate, 65025
Brazil4 sites
Santa Casa de Misericordia de Porto Alegre
Porto Alegre, Rio Grande do Sul, 90050-170
Hospital do Cancer de Pernambuco - HCP
Recife, Pernambuco, 50040-000
Clinica de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria Ltda
São Paulo, São Paulo, 01317-001
Núcleo de Pesquisa São Camilo; ONCOLOGIA CLINICA / QUIMIOTERAPIA
São Paulo, São Paulo, 04014-002
Poland4 sites
Szpital Morski Im. Pck; Oncology & Radiotherapy Dept
Gdynia, 81-519
COZL Oddzial Onkologii Klinicznej z pododdzialem Chemioterapii Dziennej
Lublin, 20-090
Centrum Onkologii - Inst.Im. Marii Sklodowskiej-Curie; Oncology
Warsaw, 02-781
DOLNOSLASKIE CENTRUM ONKOLOGII; Oddzial Chirurgii Piersi
Wroclaw, 53-413
Germany3 sites
Universitätsklinikum Dresden
Dresden, 01307
LUISENKRANKENHAUS; Senological Oncology
Düsseldorf, 40235
UNIVERSITATSKLINIKUM ERLANGEN; Department of Gynecology and Obstetrics
Erlangen, 91054
Australia2 sites
Macquarie University Hospital
Macquarie Park, New South Wales, 2109
Westmead Hospital; Medical Oncology and Pallative Care
Westmead, New South Wales, 2145
Hungary2 sites
Bacs-Kiskun Megyei Korhaz, SZTE AOK Oktato Korhaza, Onkoradiologiai Kozpont; Onkoradiologiai Kozpont
Kecskemét, 6000
Tolna Megyei Kórház, Onkológia
Szekszárd, 7100
Taiwan2 sites
National Cheng Kung Uni Hospital; Surgery
Tainan, 704
National Taiwan Uni Hospital; General Surgery
Taipei, 100
About this study
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
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).
- Conditions
- Early Breast Cancer
- Being tested
- Giredestrant, Anastrozole, Palbociclib, Surgery
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GiredestrantDrug
Also called GDC-9545, RO7197597, RG6171
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.
AnastrozoleDrug
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.
PalbociclibDrug
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.
SurgeryProcedure or 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.
| Study group | Role | What they receive |
|---|---|---|
| Giredestrant + Palbociclib | Experimental | Not described Receives: Drug: Giredestrant; Drug: Palbociclib; Procedure: Surgery |
| Anastrozole + Palbociclib | Active comparator | Not described Receives: Drug: Anastrozole; Drug: Palbociclib; Procedure: Surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, Week 2
Secondary outcomes (11)
Overall Response Rate (ORR) by Ultrasound as Determined by the Investigator
ORR was 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). Ultrasound and clinical exam were used to assess response. CR per mRECIST was defined as the disappearance of all target lesions. PR per mRECIST was defined as at least 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. An estimate of ORR and its 95% confidence interval (CI) was calculated using the Clopper-Pearson method.
Measured: Baseline up to Cycle 4 Day 1 (each cycle is 28 days)
Complete Cell Cycle Arrest (CCCA) Rate at Week 2
CCCA was defined as the percentage of participants with centrally assessed Ki67 scores ≤2.7%. The CCCA rate at Week 2 was summarized.
Measured: 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)
AE is any untoward medical occurrence in clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable \& unintended sign, symptom/disease temporally associated with use of a medicinal product, whether or not related to medicinal product. Preexisting conditions which worsen during a study also considered as AEs. Severity of AEs was determined per NCI CTCAE v5.0. Grade 1: Mild; asymptomatic/mild symptoms; clinical/diagnostic observations only; or intervention not indicated; Grade 2: Moderate; minimal, local/non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living; Grade 3: Severe/medically significant, but not immediately life-threatening: hospitalization/prolongation of hospitalization indicated; disabling/limiting self-care activities of daily living; Grade 4: Life-threatening consequences/urgent intervention indicated; Grade 5: Death related to AE.
Measured: From baseline up to 28 days after the last dose (up to approximately 24 weeks)
Change From Baseline in Respiratory Rate Over Time
Respiratory rate was measured while the participant was in a seated position.
Measured: 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
Pulse rate was measured while the participant was in a seated position.
Measured: 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 Systolic Blood Pressure Over Time
Systolic blood pressure was measured while the participant was in a seated position.
Measured: 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 Diastolic Blood Pressure Over Time
Diastolic blood pressure was measured while the participant was in a seated position.
Measured: 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 Body Temperature Over Time
Measured: 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)
Number of Participants With Shifts in Hematology Test Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline
Hematology test parameters were measured per NCI CTCAE v5.0. Grade 0 is normal, and Grades 1 to 4 represent worsening levels of the parameter outside of the normal range in the specified direction of the abnormality (high and low are above and below the range, respectively). Number of participants with shift in the hematology values from grade 0-2 at baseline to grade 3-4 at post-baseline were reported. A marked reference range for hemoglobin 12.3-15.3 grams per deciliter (g/dL), lymphocytes absolute (Abs) 1.0-4.8 10^3/microliters (uL), neutrophils total, Abs, 1.8-8.5 10^3/uL, platelet 100-450 10^9/liter (L), total leukocyte 4.4-11 10^9/L.
Measured: From baseline up to 28 days after the last dose (up to approximately 24 weeks)
Number of Participants With Shifts in Blood Chemistry Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline
Blood chemistry parameters were measured per NCI CTCAE v5.0. Grade 0=normal, and Grades 1 to 4 represent worsening levels of parameter outside of normal range in the specified direction of abnormality (high \& low are above \& below the range, respectively). Number of participants with shift in blood chemistry values from grade 0-2 at baseline to grade 3-4 at post-baseline were reported. Marked reference range for albumin 32-45 grams per liter (g/L), alkaline phosphatase 20-130 units per liter (U/L), serum glutamic pyruvic transaminase (SGPT)/ alanine transaminase (ALT) 4-36 U/L, serum glutamic oxaloacetic transaminase (SGOT)/ aspartate transaminase (AST) 8-33 U/L, calcium 2.3-2.74 millimoles per liter (mmol/L), cholesterol 3.88-6.47mmol/L, creatinine 6-12 milligrams per liter (mg/L), glucose 3.9-6.1 mmol/L, potassium 3.5-5.0 mmol/L, sodium 135-147 mmol/L, bilirubin 2-21 micromoles per liter (μmol/L), triglycerides 0.11-2.15 mmol/L, \& uric acid 2.7-7.3 milligrams per deciliter (mg/dL).
Measured: From baseline up to 28 days after the last dose (up to approximately 24 weeks)
Plasma Concentration of Giredestrant at Specified Timepoints
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2020
- Study start4 Sep 2020
- Primary completion6 Jul 2021
- Study completion24 Nov 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Early Breast CancerStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 221 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04436744
- Sponsor's protocol ID
- WO42133
- Other IDs
- 2020-001007-16
- Status last verified
- Jan 2023
- First submitted
- 16 Jun 2020
- Last updated
- 2 Feb 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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).
Publications
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.
PubMed 37657462