NCT04436744已完成2 期
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
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 221
- 试验地点
- 65
- 主要终点
- Relative Percent Change in Ki67 Scores From Baseline to Week 2
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 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
- •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
排除标准
- •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
研究组 & 干预措施
Giredestrant + Palbociclib
Experimental
干预措施: Giredestrant (Drug)
Giredestrant + Palbociclib
Experimental
干预措施: Palbociclib (Drug)
Giredestrant + Palbociclib
Experimental
干预措施: Surgery (Procedure)
Anastrozole + Palbociclib
Active Comparator
干预措施: Anastrozole (Drug)
Anastrozole + Palbociclib
Active Comparator
干预措施: Palbociclib (Drug)
Anastrozole + Palbociclib
Active Comparator
干预措施: Surgery (Procedure)
结局指标
主要结局
Relative Percent Change in Ki67 Scores From Baseline to Week 2
时间窗: Baseline, Week 2
Ki67 is a proliferation biomarker with prognostic value in ER-positive breast cancer. Ki67 scores were centrally assessed with immunohistochemistry and defined as a percentage of positively stained tumor cell nuclei among the total number of tumor cells assessed, with a potential range of 0-100%. A score of 0% indicates no tumor cell nuclei with Ki67 staining and a score of 100% indicates all tumor cell nuclei are positively stained with Ki67. The relative percentage change was calculated using Ki67 scores at Baseline and Week 2. Relative Percent Change was defined as Week 2 Ki67 percentage score/Baseline Ki67 percentage score\*100. A smaller value of relative percentage change indicates improvement.
次要结局
- Number of Participants With Adverse Events (AEs) With Severity Determined in Accordance With National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)(From baseline up to 28 days after the last dose (up to approximately 24 weeks))
- Change From Baseline in Body Temperature Over Time(Baseline; Cycles 1-2: Day 1 and Day 15; Cycles 3-4: Day 1; day of surgery (up to 2 weeks after the final dose of study treatment [approximately Week 18]) and end of study (up to approximately 24 weeks))
- Plasma Concentration of Giredestrant at Specified Timepoints(Window of Opportunity Phase: Day 1 (3 hours Postdose) and Day 15 (Predose) during Cycle 0 (the 15-day period in Window of Opportunity Phase is called Cycle 0 for PK analysis); Neoadjuvant Phase: Cycle 2 Day 1, Predose)
- Change From Baseline in Respiratory Rate Over Time(Baseline; Cycles 1-2: Day 1 and Day 15; Cycles 3-4: Day 1; day of surgery (up to 2 weeks after the final dose of study treatment [approximately Week 18]) and end of study (up to approximately 24 weeks))
- Change From Baseline in Pulse Rate Over Time(Baseline; Cycles 1-2: Day 1 and Day 15; Cycles 3-4: Day 1; day of surgery (up to 2 weeks after the final dose of study treatment [approximately Week 18]) and end of study (up to approximately 24 weeks))
- Change From Baseline in Systolic Blood Pressure Over Time(Baseline; Cycles 1-2: Day 1 and Day 15; Cycles 3-4: Day 1; day of surgery (up to 2 weeks after the final dose of study treatment [approximately Week 18]) and end of study (up to approximately 24 weeks))
- Change From Baseline in Diastolic Blood Pressure Over Time(Baseline; Cycles 1-2: Day 1 and Day 15; Cycles 3-4: Day 1; day of surgery (up to 2 weeks after the final dose of study treatment [approximately Week 18]) and end of study (up to approximately 24 weeks))
- Overall Response Rate (ORR) by Ultrasound as Determined by the Investigator(Baseline up to Cycle 4 Day 1 (each cycle is 28 days))
- Number of Participants With Shifts in Hematology Test Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline(From baseline up to 28 days after the last dose (up to approximately 24 weeks))
- Complete Cell Cycle Arrest (CCCA) Rate at Week 2(Week 2)
- Number of Participants With Shifts in Blood Chemistry Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline(From baseline up to 28 days after the last dose (up to approximately 24 weeks))
研究者
研究点 (65)
Loading locations...
相似试验
已完成
2 期
A Study of Pertuzumab in Combination With Trastuzumab Plus an Aromatase Inhibitor in Participants With Metastatic Human Epidermal Growth Factor Receptor 2 (HER2)-Positive and Hormone Receptor-Positive Advanced Breast CancerBreast CancerNCT01491737Hoffmann-La Roche258
已完成
2 期
An Open-label Study of GSK1120212 Compared With Docetaxel in Stage IV KRAS-mutant Non-small Cell Lung CancerLung Cancer, Non-Small CellNCT01362296GlaxoSmithKline134
已完成
2 期
Study to Evaluate Treatment Compliance, Efficacy and Safety of an Improved Deferasirox Formulation (Granules) in Pediatric Patients (2-<18 Years Old) With Iron OverloadTransfusion-dependent AnemiaNCT02435212Novartis Pharmaceuticals224
已完成
2 期
A Study Investigating the Efficacy and Safety of Ociperlimab and Tislelizumab and BAT1706 Combinations in Patients With Advanced HCCNCT04948697BeiGene94
撤回
2 期
A Study of Ficlatuzumab With HiDAC and HiDAC Alone in Adults With Relapsed or Refractory Acute Myeloid LeukemiaAcute Myeloid LeukemiaNCT04100330AVEO Pharmaceuticals, Inc.