Clinical Trials /

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)

NCT04436744

Description:

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).

Related Conditions:
  • Invasive Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: WO42133
  • SECONDARY ID: 2020-001007-16
  • NCT ID: NCT04436744

Conditions

  • Early Breast Cancer

Interventions

DrugSynonymsArms
GDC-9545RG6171GDC-9545 + Palbociclib
AnastrozoleAnastrozole + Palbociclib
PalbociclibAnastrozole + Palbociclib

Purpose

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).

Trial Arms

NameTypeDescriptionInterventions
GDC-9545 + PalbociclibExperimental
  • GDC-9545
  • Palbociclib
Anastrozole + PalbociclibActive Comparator
  • Anastrozole
  • Palbociclib

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

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Change in Ki67 Scores from Baseline to Week 2
Time Frame:Baseline and Week 2
Safety Issue:
Description:

Secondary Outcome Measures

Measure: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)
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Hoffmann-La Roche

Last Updated

August 7, 2020