Clinical Trials /

A Study of GDC-9545 in Postmenopausal Women With Stage I-III Operable, Estrogen Receptor-Positive Breast Cancer

NCT03916744

Description:

This study will evaluate the pharmacodynamics, pharmacokinetics, safety, and biologic activity of GDC-9545 in participants with Stage I-III operable estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, untreated breast cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of GDC-9545 in Postmenopausal Women With Stage I-III Operable, Estrogen Receptor-Positive Breast Cancer
  • Official Title: A Phase I, Multicenter, Open-Label Preoperative, Short-Term Window Study of GDC-9545 in Postmenopausal Women With Stage I-III Operable, Estrogen Receptor-Positive Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: GO40987
  • SECONDARY ID: 2018-003798-85
  • NCT ID: NCT03916744

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
GDC-9545RG6171GDC-9545 Dose Level 1

Purpose

This study will evaluate the pharmacodynamics, pharmacokinetics, safety, and biologic activity of GDC-9545 in participants with Stage I-III operable estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, untreated breast cancer.

Trial Arms

NameTypeDescriptionInterventions
GDC-9545 Dose Level 1Experimental
  • GDC-9545
GDC-9545 Dose Level 2Experimental
  • GDC-9545
GDC-9545 Dose Level 3Experimental
  • GDC-9545

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

          -  Confirmed diagnosis of breast cancer

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to
             (≤)1

          -  Adequate organ function

        Exclusion Criteria:

          -  Diagnosis of inflammatory 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

          -  Pregnant, lactating, or breastfeeding

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

Primary Outcome Measures

Measure:Change from Baseline in Tumor Cell Proliferation Measured by Ki67 Expression Between Pre- and Post-Treatment Tumor Biopsy Samples
Time Frame:Baseline and Day 15
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Number of Participants with at Least One Adverse Event and by Severity, Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0)
Time Frame:From Baseline to Day 43
Safety Issue:
Description:
Measure:Change from Baseline in Pulse Rate
Time Frame:Baseline, Days 1, 8, 15, and 43
Safety Issue:
Description:
Measure:Change from Baseline in Systolic Blood Pressure
Time Frame:Baseline, Days 1, 8, 15, and 43
Safety Issue:
Description:Systolic blood pressure will be measured while the participant is in a seated position.
Measure:Change from Baseline in Diastolic Blood Pressure
Time Frame:Baseline, Days 1, 8, 15, and 43
Safety Issue:
Description:Diastolic blood pressure will be measured while the participant is in a seated position.
Measure:Change from Baseline in Body Temperature
Time Frame:Baseline, Days 1, 8, 15, and 43
Safety Issue:
Description:Body temperature will be taken by oral or tympanic temperature.
Measure:Change from Baseline in Prothrombin Time (PT)
Time Frame:Baseline, Days 15 and 43
Safety Issue:
Description:
Measure:Change from Baseline in Activated Partial Thromboplastin Time (aPTT)
Time Frame:Baseline, Days 15 and 43
Safety Issue:
Description:
Measure:Change from Baseline in International Normalized Ratio (INR)
Time Frame:Baseline, Days 15 and 43
Safety Issue:
Description:
Measure:Plasma Concentration of GDC-9545 at Steady State
Time Frame:Day 15
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Genentech, Inc.

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