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History of Changes for Study: NCT04436744
A 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
Latest version (submitted January 5, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 June 16, 2020 None (earliest Version on record)
2 July 10, 2020 Study Status and Arms and Interventions
3 August 7, 2020 Recruitment Status, Study Status, Contacts/Locations and Oversight
4 August 17, 2020 Contacts/Locations and Study Status
5 September 16, 2020 Study Status and Contacts/Locations
6 October 15, 2020 Study Status
7 November 13, 2020 Study Status, Contacts/Locations and Arms and Interventions
8 December 11, 2020 Contacts/Locations and Study Status
9 December 18, 2020 Contacts/Locations and Study Status
10 January 8, 2021 Contacts/Locations and Study Status
11 January 22, 2021 Contacts/Locations and Study Status
12 February 12, 2021 Contacts/Locations and Study Status
13 February 24, 2021 Contacts/Locations, Study Status and Study Identification
14 March 12, 2021 Study Status and Contacts/Locations
15 March 19, 2021 Arms and Interventions, Contacts/Locations, Outcome Measures, Study Description, Study Status and Study Identification
16 April 6, 2021 Contacts/Locations and Study Status
17 April 21, 2021 Contacts/Locations and Study Status
18 May 11, 2021 Contacts/Locations and Study Status
19 June 14, 2021 Contacts/Locations and Study Status
20 July 14, 2021 Recruitment Status, Contacts/Locations, Study Status and Study Design
21 August 5, 2021 Contacts/Locations and Study Status
22 November 3, 2021 Study Status
23 January 5, 2022 Recruitment Status, Study Status and Contacts/Locations
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Study NCT04436744
Submitted Date:  June 16, 2020 (v1)

Open or close this module Study Identification
Unique Protocol ID: WO42133
Brief Title: A 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
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
Secondary IDs: 2020-001007-16 [EudraCT Number]
Open or close this module Study Status
Record Verification: June 2020
Overall Status: Not yet recruiting
Study Start: August 31, 2020
Primary Completion: September 15, 2021 [Anticipated]
Study Completion: February 2, 2022 [Anticipated]
First Submitted: June 16, 2020
First Submitted that
Met QC Criteria:
June 16, 2020
First Posted: June 18, 2020 [Actual]
Last Update Submitted that
Met QC Criteria:
June 16, 2020
Last Update Posted: June 18, 2020 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Hoffmann-La Roche
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: No
Open or close this module Study Description
Brief Summary:

This is a randomized, multicenter, open-label, two-arm, Phase II study to evaluate the efficacy, safety, and pharmacokinetics of GDC-9545 versus anastrozole (in the window-of-opportunity phase) and GDC-9545 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:
Open or close this module Conditions
Conditions: Early Breast Cancer
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 2
Interventional Study Model: Parallel Assignment
Number of Arms: 2
Masking: None (Open Label)
Allocation: Randomized
Enrollment: 215 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: GDC-9545 + Palbociclib Drug: GDC-9545
During the window-of-opportunity phase (first 2 weeks) GDC-9545 will be taken orally once per day (QD) as a single agent. During the neoadjuvant treatment phase, GDC-9545 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.
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.
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Change in Ki67 Scores from Baseline to Week 2
[ Time Frame: Baseline and Week 2 ]

Secondary Outcome Measures:
1. 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)
[ Time Frame: Baseline and Cycle 4 Day 1 (1 cycle is 28 days) ]

2. 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
[ Time Frame: Week 2 ]

3. 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)
[ Time Frame: From Baseline until 28 days after final dose of study treatment (up to 24 weeks) ]

4. Change from Baseline in Respiratory Rate Over Time
[ Time Frame: From Baseline until 28 days after final dose of study treatment (up to 24 weeks) ]

5. Change from Baseline in Pulse Rate Over Time
[ Time Frame: From Baseline until 28 days after final dose of study treatment (up to 24 weeks) ]

6. Change from Baseline in Systolic Blood Pressure Over Time
[ Time Frame: From Baseline until 28 days after final dose of study treatment (up to 24 weeks) ]

7. Change from Baseline in Diastolic Blood Pressure Over Time
[ Time Frame: From Baseline until 28 days after final dose of study treatment (up to 24 weeks) ]

8. Change from Baseline in Body Temperature Over Time
[ Time Frame: From Baseline until 28 days after final dose of study treatment (up to 24 weeks) ]

9. Number of Participants with Clinical Laboratory Abnormalities in Hematology Test Parameters
[ Time Frame: From Baseline until 28 days after final dose of study treatment (up to 24 weeks) ]

10. Number of Participants with Clinical Laboratory Abnormalities in Blood Chemistry Test Parameters
[ Time Frame: From Baseline until 28 days after final dose of study treatment (up to 24 weeks) ]

11. Plasma Concentration of GDC-9545 at Specified Timepoints
[ Time Frame: Cycle 0 Days 1 and 15, Cycle 2 Day 1 (1 cycle is 28 days), and End of Study Visit (up to 24 weeks) ]

Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: Female
Gender Based:
Accepts Healthy Volunteers: No
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
Open or close this module Contacts/Locations
Central Contact Person: Reference Study ID Number: WO42133 www.roche.com/about_roche/roche_worldwide.htm
Telephone: 888-662-6728 (U.S. Only)
Email: global-roche-genentech-trials@gene.com
Study Officials: Clinical Trials
Study Director
Hoffmann-La Roche
Locations:
Open or close this module IPDSharing
Plan to Share IPD: 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).

Supporting Information:
Time Frame:
Access Criteria:
URL:
Open or close this module References
Citations:
Links:
Available IPD/Information:

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U.S. National Library of Medicine | U.S. National Institutes of Health | U.S. Department of Health & Human Services