A Phase II Randomized, Double-Blind Study of Neoadjuvant Letrozole Plus GDC-0032 Versus Letrozole Plus Placebo in Postmenopausal Women With ER-positive/HER2-negative, Early Stage Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 334
- 试验地点
- 117
- 主要终点
- Percentage of Participants With Total Pathologic Complete Response (Total pCR), Defined as Having pCR in Both Breast and Axilla, Using American Joint Committee on Cancer (AJCC) Staging System
研究概览
简要总结
This is a two-arm, randomized, double-blind, multicenter, pre-operative study to evaluate the effect of combining letrozole and GDC-0032 (also known as taselisib) versus letrozole and placebo in postmenopausal women with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2 (HER2) untreated, Stage I-III operable breast cancer. Participants will be randomized into one of the two treatment arms with a 1:1 randomization ratio. Letrozole at 2.5 milligrams (mg) will be dosed once daily plus either Taselisib at 4 mg (two 2-mg tablets) or placebo on a 5 days-on/ 2 days-off schedule for a total of 16 weeks.
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
- Double (Participant, Investigator)
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
- •Female participants
- •Postmenopausal status
- •Histologically confirmed invasive breast carcinoma, with all of the following characteristics: (i) Primary tumor greater than or equal to (>/=) 2 centimeters (cm) in largest diameter (cT1-3) by MRI; (ii) Stage I to operable Stage III breast cancer; (iii) Documented absence of distant metastases (M0)
- •Estrogen receptor-positive (ER+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer
- •Breast cancer eligible for primary surgery
- •Tumor tissue from formalin-fixed paraffin-embedded cores (FFPE) core biopsy of breast primary tumor that is confirmed as evaluable for phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutation status by central histopathology laboratory
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Fasting glucose less than or equal to (</=) 125 milligrams per deciliter (mg/dL)
- •Adequate hematological, renal, and hepatic function
- •Absence of any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
- •Ability and willingness to comply with study visits, treatment, testing, and to comply with the protocol, in the investigator's judgment
排除标准
- •Any prior treatment for primary invasive breast cancer
- •Participants with cT4 or cN3 stage breast tumors
- •Bilateral invasive, multicentric, or metastatic breast cancer
- •Participants who have undergone excisional biopsy of primary tumor and/or axillary lymph nodes or sentinel lymph node biopsy
- •Type 1 or 2 diabetes requiring antihyperglycemic medication
- •Inability or unwillingness to swallow pills
- •Malabsorption syndrome or other condition that would interfere with enteric absorption
- •History of prior or currently active small or large intestine inflammation (such as Crohn's disease or ulcerative colitis). Any predisposition for gastrointestinal (GI) toxicity requires prior approval from the Medical Monitor.
- •Congenital long QT syndrome or QT interval corrected using Fridericia's formula (QTcF) >470 milliseconds (msec)
- •Diffusing capacity of the lungs for carbon monoxide (DLCO) <60% of the predicted values
- •Clinically significant (i.e., active) cardiovascular disease, uncontrolled hypertension, unstable angina, history of myocardial infarction, cardiac failure class II-IV
- •Any contraindication to MRI examination
- •Active infection requiring intravenous antibiotics
- •Participants requiring any daily supplemental oxygen
- •Clinically significant history of liver disease, including viral or other known hepatitis, current alcohol abuse, or cirrhosis
- •Any other diseases, active or uncontrolled pulmonary dysfunction, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, that may affect the interpretation of the results, or renders the participants at high risk from treatment complications
- •Significant traumatic injury within 3 weeks prior to initiation of study treatment
- •Major surgical procedure within 4 weeks prior to initiation of study treatment
- •Inability to comply with study and follow-up procedures
- •History of other malignancy within 5 years prior to screening, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer
研究组 & 干预措施
Letrozole + Placebo
Participants will receive 2.5 mg letrozole tablets orally QD along with placebo on a 5-days-on/2-days-off schedule for a total of 16 weeks.
干预措施: Letrozole (Drug)
Letrozole + Placebo
Participants will receive 2.5 mg letrozole tablets orally QD along with placebo on a 5-days-on/2-days-off schedule for a total of 16 weeks.
干预措施: Placebo (Other)
Letrozole + Taselisib
Participants will receive 2.5 milligrams (mg) letrozole tablets orally once daily (QD) along with taselisib tablets at 4 mg (two 2 mg tablets) orally on a 5 days-on/2 days-off schedule for a total of 16 weeks.
干预措施: Letrozole (Drug)
Letrozole + Taselisib
Participants will receive 2.5 milligrams (mg) letrozole tablets orally once daily (QD) along with taselisib tablets at 4 mg (two 2 mg tablets) orally on a 5 days-on/2 days-off schedule for a total of 16 weeks.
干预措施: Taselisib (Drug)
结局指标
主要结局
Percentage of Participants With Total Pathologic Complete Response (Total pCR), Defined as Having pCR in Both Breast and Axilla, Using American Joint Committee on Cancer (AJCC) Staging System
时间窗: From Baseline to 16 weeks
Total pCR was assessed by local pathology review on samples taken at surgery following completion of neoadjuvant therapy. tpCR was defined as the absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes ( i.e., ypT0/Tis, ypN0 in the AJCC staging system, 7th edition).
Percentage of Participants With OR by Centrally Assessed Breast MRI Via mRECIST Version 1.1 in Phosphatidylinositol-4,5-Bisphosphate 3-Kinase, Catalytic Subunit Alpha (PIK3CA) Mutant (MT) Participants
时间窗: From Baseline to 16 weeks
ORR was defined as proportion of participants achieving CR or PR. As per modified RECIST v1.1, CR: disappearance of all target lesions, PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Percentage of Participants With Objective Response (OR) by Centrally Assessed Breast Magnetic Resonance Imaging (MRI) Via Modified Response Evaluation Criteria in Solid Tumors (mRECIST) Version 1.1
时间窗: From Baseline to 16 weeks
Objective response rate (ORR) was defined as proportion of participants achieving complete response (CR) or partial response (PR). As per modified RECIST v1.1, CR: disappearance of all target lesions, PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Percentage of Participants With Total pCR , Defined as Having pCR in Both Breast and Axilla, Using AJCC Staging System in PIK3CA MT Participants
时间窗: From Baseline to 16 weeks
Total pCR was assessed by local pathology review on samples taken at surgery following completion of neoadjuvant therapy. tpCR was defined as the absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes (i.e., ypT0/Tis, ypN0 in the AJCC staging system, 7th edition).
次要结局
- Percentage of Participants With OR by Breast Ultrasound Via mRECIST Version 1.1 in PIK3CA WT Participants(From Baseline to 16 weeks)
- Percentage of Participants With OR by Mammography Via mRECIST Version 1.1 in PIK3CA WT Participants(From Baseline to 16 weeks)
- Percentage of Participants With OR by Clinical Breast Exam (Palpation) Via mRECIST Version 1.1 in PIK3CA WT Participants(From Baseline to 16 weeks)
- Percent Change From Baseline to Surgery in Enhancing Tumor Volume as Measured by Breast MRI(From Baseline to Surgery (Weeks 17-18))
- Percentage of Participants With OR by Mammography Via mRECIST Version 1.1 in PIK3CA MT Participants(From Baseline to 16 weeks)
- Percentage of Participants With OR by Clinical Breast Exam (Palpation) Via mRECIST Version 1.1 in PIK3CA MT Participants(From Baseline to 16 weeks)
- Percentage of Participants With Total pCR Defined as Having pCR in Both Breast and Axilla, Using AJCC Staging System in PIK3CA WT Participants(From Baseline to 16 weeks)
- Preoperative Endocrine Prognostic Index (PEPI ) Score(Week 16)
- Percentage of Participants With OR by Centrally Assessed Breast MRI Via mRECIST Version 1.1 in PIK3CA Wildtype (WT) Participants(From Baseline to 16 weeks)
- Percentage of Participants With OR by Breast Ultrasound Via mRECIST Version 1.1 in PIK3CA MT Participants(From Baseline to 16 weeks)
- Central Assessments of Changes in Ki67 Levels(From Baseline to Week 3 and Surgery (Weeks 17-18); and Week 3 to Surgery (Weeks 17-18))
- Mean Score for Health-Related Quality of Life Measured by the European Organization for Research C30 (EORTC QLQ-C30)(Weeks 1, 5, 9, 13, 16, 4-week Post-Surgery)
- Mean Score for Treatment of Cancer Quality of Life Questionnaire BR23 (QLQ-BR23)(Weeks 1, 5, 9, 13, 16, 4-week Post-Surgery)
- Percentage of Participants With Adverse Events(Baseline up to 22 weeks)