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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 75
- 试验地点
- 15
- 主要终点
- Change From Baseline in Tumor Cell Proliferation, as Measured by the Proportion of Nuclei Staining Ki67-Positive at Surgery Relative to Baseline in Pre- and Post-Treatment Tumor Biopsy Samples
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Giredestrant 10 mg
干预措施: Giredestrant (Drug)
Giredestrant 10 mg
干预措施: Surgery (Procedure)
Giredestrant 30 mg
干预措施: Giredestrant (Drug)
Giredestrant 30 mg
干预措施: Surgery (Procedure)
Giredestrant 100 mg
干预措施: Giredestrant (Drug)
Giredestrant 100 mg
干预措施: Surgery (Procedure)
结局指标
主要结局
Change From Baseline in Tumor Cell Proliferation, as Measured by the Proportion of Nuclei Staining Ki67-Positive at Surgery Relative to Baseline in Pre- and Post-Treatment Tumor Biopsy Samples
时间窗: Baseline and Surgery (Day 15)
The biological response to the study treatment was assessed by measuring changes in cell proliferation (Ki67 expression) using formalin-fixed paraffin-embedded histopathology sections of the tumor biopsy specimens taken at baseline and at day of surgery. Baseline was defined as a sample taken prior to initiation of study drug. The results show the proportion of nuclei staining Ki67-positive (Ki67+) in the tumor biopsy sample taken post-treatment (at surgery) relative to that in the pre-treatment sample (at baseline).
Change From Baseline in Tumor Cell Proliferation, as Measured by the Difference in the Percentage of Nuclei Staining Ki67-Positive at Surgery Compared With Baseline in Pre- and Post-Treatment Tumor Biopsy Samples
时间窗: Baseline and Surgery (Day 15)
The biological response to the study treatment was assessed by measuring changes in cell proliferation (Ki67 expression) using formalin-fixed paraffin-embedded histopathology sections of the tumor biopsy specimens taken at baseline and at day of surgery. Baseline was defined as a sample taken prior to initiation of study drug. The results show the percentage of nuclei staining Ki67-positive (Ki67+) in the pre- and post-treatment tumor biopsy samples (taken at baseline and surgery, respectively) and the absolute difference in the percentage of Ki67+ nuclei between the two samples (calculated as surgery minus baseline).
次要结局
- Percentage of Participants With Abnormal Vital Signs During Treatment(Baseline, Days 1, 8, and 15)
- 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)(From Baseline to Day 43)
- Change From Baseline in Pulse Rate(Baseline, Day 8, Surgery (Day 15), and Post-Surgery (Day 43))
- Change From Baseline in Systolic Blood Pressure(Baseline, Day 8, Surgery (Day 15), and Post-Surgery (Day 43))
- Change From Baseline in Diastolic Blood Pressure(Baseline, Day 8, Surgery (Day 15), and Post-Surgery (Day 43))
- Change From Baseline in Body Temperature(Baseline, Day 8, Surgery (Day 15), and Post-Surgery (Day 43))
- Percentage of Participants With Laboratory Abnormalities in Hematology Tests During Treatment, Among Participants Without the Abnormality at Baseline(Baseline, Days 1, 8, and 15)
- Percentage of Participants With Laboratory Abnormalities in Blood Chemistry and Coagulation Tests During Treatment, Among Participants Without the Abnormality at Baseline(Baseline, Days 1, 8, and 15)
- Percentage of Participants With Abnormal Electrocardiogram Parameters During Treatment(Baseline, Days 1, 8, and 15)
- Plasma Concentration of Giredestrant at Steady State by Dose Level(Predose on day of surgery (Day 15), or prior to biopsy (Day 14))