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)

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Completed

CT.gov ID

NCT04436744

Collaborator

(none)

221

Enrollment

Locations

Arms

14.7

Actual Duration (Months)

3.4

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Early Breast Cancer	Drug: Giredestrant Drug: Anastrozole Drug: Palbociclib Procedure: Surgery	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

221 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Sep 4, 2020

Actual Primary Completion Date :

Jul 6, 2021

Actual Study Completion Date :

Nov 24, 2021

Arms and Interventions

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: 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. 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.

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: 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.

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.

Outcome Measures

Primary Outcome Measures

Change in Ki67 Scores from Baseline to Week 2 [Baseline and Week 2]

Secondary Outcome Measures

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)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

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

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Hoffmann-La Roche

ClinicalTrials.gov Identifier:

NCT04436744

Other Study ID Numbers:

WO42133
2020-001007-16

First Posted:

Jun 18, 2020

Last Update Posted:

Jun 27, 2022

Last Verified:

Jun 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Breast Neoplasms

Palbociclib

Anastrozole

Study Results

No Results Posted as of Jun 27, 2022