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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)

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ClinicalTrials.gov Identifier: NCT04436744
Recruitment Status : Completed
First Posted : June 18, 2020
Last Update Posted : January 14, 2022
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE June 16, 2020
First Posted Date  ICMJE June 18, 2020
Last Update Posted Date January 14, 2022
Actual Study Start Date  ICMJE September 4, 2020
Actual Primary Completion Date July 6, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 16, 2020)
Change in Ki67 Scores from Baseline to Week 2 [ Time Frame: Baseline and Week 2 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 19, 2021)
  • 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) ]
  • 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 ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • Plasma Concentration of Giredestrant 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) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: June 16, 2020)
  • 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) ]
  • 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 ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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)
Official Title  ICMJE 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
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).

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Early Breast Cancer
Intervention  ICMJE
  • 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: 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.
Study Arms  ICMJE
  • Experimental: Giredestrant + Palbociclib
    Interventions:
    • Drug: Giredestrant
    • Drug: Palbociclib
    • Procedure: Surgery
  • Active Comparator: Anastrozole + Palbociclib
    Interventions:
    • Drug: Anastrozole
    • Drug: Palbociclib
    • Procedure: Surgery
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 14, 2021)
221
Original Estimated Enrollment  ICMJE
 (submitted: June 16, 2020)
215
Actual Study Completion Date  ICMJE November 24, 2021
Actual Primary Completion Date July 6, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Brazil,   Germany,   Hungary,   Korea, Republic of,   Poland,   Russian Federation,   Spain,   Taiwan,   Ukraine,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04436744
Other Study ID Numbers  ICMJE WO42133
2020-001007-16 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description:

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).

Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date January 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP