NCT04961996进行中（未招募）3 期
A Phase III, Randomized, Open-Label, Multicenter Study Evaluating the Efficacy and Safety of Adjuvant Giredestrant Compared With Physician's Choice of Adjuvant Endocrine Monotherapy in Patients With Estrogen Receptor-Positive, HER2-Negative Early Breast Cancer
适应症
干预措施
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 4,170
- 试验地点
- 1,057
- 主要终点
- Invasive Disease-Free Survival (IDFS), Excluding Second Primary Non-Breast Cancers
研究概览
简要总结
This is a Phase III, global, randomized, open-label, multicenter, study evaluating the efficacy and safety of adjuvant giredestrant compared with physician's choice of endocrine therapy in participants with medium- and high-risk Stage I-III histologically confirmed estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative early breast cancer.
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
- All
- 接受健康志愿者
- 否
入选标准
- •Documented estrogen receptor (ER)-positive and HER2-negative breast tumor, as assessed locally on a primary disease specimen
- •Participants who have multicentric (the presence of two of more tumor foci within different quadrants of the same breast) and/or multifocal (the presence of two or more tumor foci within a single quadrant of the breast) breast cancer are also eligible if all examined tumors meet pathologic criteria for ER positivity and HER2 negativity
- •Participants must have undergone definitive surgery of their primary breast tumor(s) and axillary lymph nodes (axillary lymph node dissection [ALND] and/or sentinel lymph node biopsy [SLNB])
- •Participants who received or will be receiving adjuvant chemotherapy must have completed adjuvant chemotherapy prior to randomization. Participants may also have received neoadjuvant chemotherapy. A washout period of at least 21 days is required between last adjuvant chemotherapy dose and randomization.
- •Resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to NCI CTCAE v5.0 Grade 1 or better (except alopecia, Grade ≤2 peripheral neuropathy, arthralgia or other toxicities not considered a safety risk for the participant per the investigator's judgment)
- •Participants have received (neo)adjuvant chemotherapy and/or had surgery and had no prior endocrine therapy are eligible, provided that they are enrolled within 12 months following definitive breast cancer surgery
- •Participants who have confirmed availability of an untreated primary breast tumor tissue specimen suitable for biomarker testing (i.e., representative archived formalin-fixed, paraffin-embedded [FFPE] tissue block [preferred] or 15-20 slides containing unstained, freshly cut, serial sections), with associated de-identified pathology report is required. Although 15-20 slides are preferred, if only 10-14 slides are available, the individual may still be eligible for the study.
- •Participants with node-positive and node-negative disease are eligible provided they meet additional risk criteria as defined in the protocol
- •Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1, or 2
- •Able and willing to swallow, retain, and absorb oral medication
- •Adequate organ function
排除标准
- •Pregnant or breastfeeding, or intending to become pregnant during the study or within 10 days after the final dose of giredestrant, or within the time period specified per local prescribing guidelines after the final dose of the endocrine therapy of physician's choice
- •Received treatment with investigational therapy within 28 days prior to initiation of study treatment or is currently enrolled in any other type of medical research judged by the sponsor not to be scientifically or medically compatible with this study
- •Receiving or planning to receive a CDK4/6 inhibitor as (neo)adjuvant therapy. A short course of up to 12 weeks of neoadjuvant or adjuvant treatment with CDK4/6 inhibitor therapy prior to randomization is allowed.
- •Active cardiac disease or history of cardiac dysfunction
- •Diagnosed with Stage IV breast cancer
- •A history of any prior (ipsilateral and/or contralateral) invasive breast cancer or ductal carcinoma in situ (DCIS). Participants with a history of contralateral DCIS treated by only local regional therapy at any time may be eligible.
- •A history of any other malignancy within 3 years prior to screening, except for appropriately treated carcinoma in situ of the cervix, nonmelanoma skin carcinoma, or Stage I uterine cancer
- •Any prior endocrine treatment with selective ER modulators (e.g., tamoxifen), degraders, or aromatase inhibitors. A short course of neoadjuvant or adjuvant endocrine therapy (up to 12 weeks) is allowed.
- •Clinically significant liver disease consistent with Child-Pugh Class B or C, including active hepatitis (e.g., hepatitis B virus [HBV] or hepatitis C virus [HCV]), current alcohol abuse, cirrhosis, or positive test for viral hepatitis
- •Treatment with strong CYP3A4 inhibitors or inducers within 14 days or 5 drug elimination half-lives (whichever is longer) prior to initiation of study treatment
- •Known allergy or hypersensitivity to any of the study drugs or any of their excipients
- •Pre- and perimenopausal participants or male participants who have a known hypersensitivity to LHRH agonists
- •A documented history of hemorrhagic diathesis, coagulopathy, or thromboembolism
- •Renal dysfunction that requires dialysis
- •A major surgical procedure unrelated to breast cancer within 28 days prior to randomization
- •A serious infection requiring oral or IV antibiotics within 14 days prior to screening or other clinically significant infection (e.g., COVID-19) within 14 days prior to screening
- •Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes an individual's safe participation in and completion of the study
- •Unable or unwilling to comply with the requirements of the protocol in the opinion of the investigator
研究组 & 干预措施
Arm A: Giredestrant
Experimental
干预措施: Giredestrant (Drug)
Arm A: Giredestrant
Experimental
干预措施: LHRH Agonist (Drug)
Arm B: Physician's Choice of Endocrine Therapy
Active Comparator
干预措施: Physician's Choice of Endocrine Therapy (Drug)
Arm B: Physician's Choice of Endocrine Therapy
Active Comparator
干预措施: LHRH Agonist (Drug)
结局指标
主要结局
Invasive Disease-Free Survival (IDFS), Excluding Second Primary Non-Breast Cancers
时间窗: From randomization to first occurrence of an IDFS event (up to 10 years)
次要结局
- Change from Baseline in the Mean Global Health Status/Quality of Life (QoL) Scale Score at Specified Timepoints, Assessed Using the EORTC QLQ-C30(Baseline (Cycle 1) and Cycles 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, and 60 (1 cycle is 28 days) of treatment, once every 6 months during the first 2 years of post-treatment follow-up and annually for 3 years thereafter (up to 10 years))
- Invasive Disease-Free Survival (IDFS), Including Second Primary Non-Breast Cancers(From randomization to first occurrence of an IDFS event (up to 10 years))
- Change from Baseline in the Mean Role Functioning Scale Score at Specified Timepoints, Assessed Using the EORTC QLQ-C30(Baseline (Cycle 1) and Cycles 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, and 60 (1 cycle is 28 days) of treatment, once every 6 months during the first 2 years of post-treatment follow-up and annually for 3 years thereafter (up to 10 years))
- Distant Recurrence-Free Interval (DRFI)(From randomization to first occurrence of a DFRI event (up to 10 years))
- Change from Baseline in the Mean Physical Functioning Scale Score at Specified Timepoints, Assessed Using the EORTC QLQ-C30(Baseline (Cycle 1) and Cycles 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, and 60 (1 cycle is 28 days) of treatment, once every 6 months during the first 2 years of post-treatment follow-up and annually for 3 years thereafter (up to 10 years))
- Change from Baseline in the EQ 5D-5L Index-Based Score at Specified Timepoints(Baseline (Cycle 1) and Cycles 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, and 60 (1 cycle is 28 days) of treatment, once every 6 months during the first 2 years of post-treatment follow-up and annually for 3 years thereafter (up to 10 years))
- Incidence and Severity of Adverse Events, with Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI-CTCAE v5.0)(From start of treatment until 28 days after the final dose of study treatment (up to 5 years))
- Substudy: Incidence of Grade ≥3 Adverse Events with Giredestrant in Combination with Abemaciclib(From first dose of study treatment until 28 days after the last dose of treatment with the combination of giredestrant and abemaciclib or until the end of Year 2, whichever occurs first (up to 2 years))
- Overall Survival(From randomization to death from any cause (up to 10 years))
- Plasma Concentrations of Giredestrant at Specified Timepoints(Predose and 3-4 hours postdose on Day 1 of Cycles 1 and 2, and predose on Day 1 of Cycles 3 and 6 (1 cycle is 28 days))
- Disease-Free Survival (DFS)(From randomization to first occurrence of a DFS event (up to 10 years))
- Locoregional Recurrence-Free Interval (LRRFI)(From randomization to first occurrence of a LRRFI event (up to 10 years))
- Mean Physical Functioning Scale Score at Specified Timepoints, Assessed Using the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)(Baseline (Cycle 1) and Cycles 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, and 60 (1 cycle is 28 days) of treatment, once every 6 months during the first 2 years of post-treatment follow-up and annually for 3 years thereafter (up to 10 years))
- Mean Role Functioning Scale Score at Specified Timepoints, Assessed Using the EORTC QLQ-C30(Baseline (Cycle 1) and Cycles 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, and 60 (1 cycle is 28 days) of treatment, once every 6 months during the first 2 years of post-treatment follow-up and annually for 3 years thereafter (up to 10 years))
- Change from Baseline in the EQ 5D-5L Visual Analogue Scale (VAS) Score at Specified Timepoints(Baseline (Cycle 1) and Cycles 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, and 60 (1 cycle is 28 days) of treatment, once every 6 months during the first 2 years of post-treatment follow-up and annually for 3 years thereafter (up to 10 years))
- Mean Global Health Status/Quality of Life (QoL) Scale Score at Specified Timepoints, Assessed Using the EORTC QLQ-C30(Baseline (Cycle 1) and Cycles 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, and 60 (1 cycle is 28 days) of treatment, once every 6 months during the first 2 years of post-treatment follow-up and annually for 3 years thereafter (up to 10 years))
- Substudy: Incidence and Severity of Adverse Events with Giredestrant in Combination with Abemaciclib, with Severity Determined According to NCI-CTCAE v5.0(From first dose of study treatment until 28 days after the last dose of treatment with the combination of giredestrant and abemaciclib or until the end of Year 2, whichever occurs first (up to 2 years))
研究者
研究点 (1057)
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