Clinical Trials/NCT04436744

NCT04436744

Completed

Phase 2

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

Hoffmann-La Roche65 sites in 9 countries221 target enrollmentSeptember 4, 2020

ConditionsEarly Breast Cancer

InterventionsGiredestrant Palbociclib Surgery Anastrozole

DrugsGiredestrant Anastrozole Palbociclib

Overview

Phase: Phase 2
Intervention: Giredestrant
Conditions: Early Breast Cancer
Sponsor: Hoffmann-La Roche
Enrollment: 221
Locations: 65
Primary Endpoint: Relative Percent Change in Ki67 Scores From Baseline to Week 2
Status: Completed
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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).

Registry

clinicaltrials.gov

Start Date

September 4, 2020

End Date

November 24, 2021

Last Updated

3 years ago

Study Type

Interventional

Study Design

Parallel

Sex

Female

Investigators

Sponsor

Hoffmann-La Roche

Responsible Party

Sponsor

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

Arms & Interventions

Giredestrant + Palbociclib

Intervention: Giredestrant

Giredestrant + Palbociclib

Intervention: Palbociclib

Giredestrant + Palbociclib

Intervention: Surgery

Anastrozole + Palbociclib

Intervention: Anastrozole

Anastrozole + Palbociclib

Intervention: Palbociclib

Anastrozole + Palbociclib

Intervention: Surgery

Outcomes

Primary Outcomes

Relative Percent Change in Ki67 Scores From Baseline to Week 2

Time Frame: Baseline, 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.

Secondary Outcomes

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)(From baseline up to 28 days after the last dose (up to approximately 24 weeks))
Change From Baseline in Body Temperature Over Time(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))
Plasma Concentration of Giredestrant at Specified Timepoints(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)
Change From Baseline in Respiratory Rate Over Time(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(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(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(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))
Overall Response Rate (ORR) by Ultrasound as Determined by the Investigator(Baseline up to Cycle 4 Day 1 (each cycle is 28 days))
Number of Participants With Shifts in Hematology Test Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline(From baseline up to 28 days after the last dose (up to approximately 24 weeks))
Complete Cell Cycle Arrest (CCCA) Rate at Week 2(Week 2)
Number of Participants With Shifts in Blood Chemistry Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline(From baseline up to 28 days after the last dose (up to approximately 24 weeks))