A Study to Evaluate 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)
Condition: Early Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Giredestrant; Anastrozole; Palbociclib; Surgery
Intervention description: 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.; 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.; 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.; 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.
Intervention MeSH terms: Palbociclib; Anastrozole
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 221.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

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).
    

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