A Study of Giredestrant (GDC-9545) in Postmenopausal Women With Stage I-III Operable, Estrogen Receptor-Positive Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Giredestrant; Surgery
Intervention description: Giredestrant will be administered orally once daily (QD) starting on Day 1 up to and including the day of surgery (if allowed per local process) on Day 15 (+/-2 days).; Breast cancer surgery will take place on Day 15 (+/-2 days).
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 75.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This study will evaluate the pharmacodynamics, pharmacokinetics, safety, and biologic
      activity of giredestrant in participants with Stage I-III operable estrogen receptor
      (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, untreated breast
      cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Ability to comply with the study protocol, in the investigator's judgment

          -  Histologically confirmed invasive breast carcinoma, with all of the following
             characteristics: Primary tumor greater than or equal to (≥)1.5 centimeters (cm) in
             largest diameter by ultrasound; Stage I-III operable breast cancer; Documentation
             confirming the absence of distant metastasis (M0) as determined by institutional
             practice.

          -  ER-positive tumor and HER2-negative breast cancer as per local laboratory testing

          -  Postmenopausal status

          -  Breast cancer eligible for primary surgery

          -  Submission of a representative tumor tissue specimen

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to
             (≤)1

          -  Adequate organ function

        Exclusion Criteria:

          -  Diagnosis of inflammatory breast cancer

          -  Diagnosis of bilateral breast cancer

          -  Concurrent use of hormone replacement therapies

          -  Previous systemic or local treatment for the primary breast cancer currently under
             investigation

          -  Concurrent treatment with other experimental drugs or participation in another
             clinical trial with any investigational drug within 30 days prior to study entry

          -  Current treatment with any systemic anti-cancer therapies

          -  Major surgery within 4 weeks prior to enrollment

          -  Radiation therapy within 2 weeks prior to enrollment

          -  Diagnosis of any secondary malignancy within 3 years prior to enrollment, except for
             appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or
             Stage I uterine cancer

          -  Active inflammatory bowel disease or chronic diarrhea, short bowel syndrome, or upper
             gastrointestinal surgery including gastric resection

          -  Known HIV infection

          -  Known clinically significant history of liver disease consistent with Child-Pugh Class
             B or C, including active viral or other hepatitis, current alcohol abuse, or cirrhosis

          -  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 giredestrant or any of its excipients

          -  Any condition requiring anti-coagulants, such as warfarin, heparin, or thrombolytic
             drugs

          -  History of documented hemorrhagic diathesis or coagulopathy

          -  History or presence of symptomatic bradycardia or sick sinus syndrome

          -  Baseline heart rate ≤55 beats per minute (bpm) prior to enrollment

          -  History or presence of an abnormal electrocardiogram (ECG) that is clinically
             significant in the investigator's opinion, including complete left bundle branch
             block, second- or third-degree heart block, or evidence of prior myocardial infarction

          -  QT interval corrected through use of Fridericia's formula (QTcF) >470 milliseconds
             demonstrated by at least two ECGs >30 minutes apart

          -  History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias such
             as structural heart disease, coronary heart disease, clinically significant
             electrolyte abnormalities, or family history of sudden unexplained death or long QT
             syndrome

          -  Current treatment with medications that are well known to prolong the QT interval

          -  History or presence of uncontrolled hypothyroidism

          -  Any other disease, metabolic dysfunction, physical examination finding, or clinical
             laboratory finding that, in the investigator's opinion, gives reasonable suspicion of
             a disease or condition that contraindicates the use of an investigational drug or that
             may affect the interpretation of the results or render the patient at high risk from
             treatment complications