Double-Blind Placebo-Controlled Randomized Phase III Trial of Fulvestrant and Ipatasertib as Treatment for Advanced HER-2 Negative and Estrogen Receptor Positive (ER+) Breast Cancer Following Progression on First Line CDK 4/6 Inhibitor and Aromatase Inhibitor
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 250
- 试验地点
- 39
- 主要终点
- Number of Participants With Progression-free Survival (PFS) Using RECIST 1.1
研究概览
简要总结
The purpose of this study is to find out whether a new drug, Ipatasertib, can slow the growth of advanced breast cancer when added to standard therapy (Fulvestrant).
详细描述
Patients enrolled in this study will receive either Ipatasertib plus Fulvestrant or placebo (a substance that looks like the study drug but does not have any active or medicinal ingredient) plus Fulvestant. The study will provide information about the ability of Ipatasertib plus Fulvestrant to control the cancer, the side effects and safety of the treatment, how patients feel while taking the treatment and associated costs.
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
- Triple (Participant, Care Provider, Investigator)
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
- •Histologically and/or cytologically confirmed ER positive, HER-2 negative breast cancer
- •Female patients must be post-menopausal; female patients who are pre-menopausal must have ovarian suppression using LHRH agonist while on study
- •Clinical and/or radiographic progression during treatment with or within 28 days after discontinuation of first line of treatment with a CDK 4/6 inhibitor and an aromatase inhibitor (AI) for advanced/metastatic disease
- •Evidence of clinically and/or radiologically documented disease
- •≥ 18 years of age
- •ECOG performance status of 0 or 1
- •No concurrent anti-cancer therapy and must satisfy the following criteria for previous therapy
- •Must not have received more than one prior line of treatment with a CDK 4/6 inhibitor and an AI in the advanced disease setting.
- •Treatment with CDK 4/6 inhibitor and AI must have been the most recent treatment prior to registration for this study
- •Adequate hematology and organ function, in the absence of growth factors
- •Absolute neutrophils > 1.5 x 10^9/L
- •Platelets ≥ 100 x 10^9/L
- •Hemoglobin > 90 g/L
- •Total Bilirubin ≤ 1.5 x ULN (upper limit of normal) or ≤ 3 x ULN if confirmed Gilbert's Syndrome
- •ALT and AST ≤ 2.5 x ULN (or ≤ 5.0 x ULN if liver or bone metastasis)
- •Alkaline phosphatase ≤ 2.0 x ULN (or ≤ 5.0 x ULN if liver metastases, ≤ 7.0 x ULN if bone metastasis)
- •Fasting glucose ≤ 8.3 mmol/L
- •HbA1c ≤ 7.5%
- •Serum albumin ≥ 30 g/L
- •INR ≤ 1.2
- •Serum Creatinine or Creatinine clearance ≤ 1.5 x ULN or ≥ 50 mL/min; measured directly by 24-hour urine sampling or as calculated by Crockcroft and Gault equation
排除标准
- •Untreated or symptomatic CNS metastases, radiation treatment for CNS metastases within 28 days
- •Active inflammatory bowel disease, bowel inflammation, inability to swallow oral medication or GI condition that alters oral absorption
- •Prior treatment with fulvestrant, selective estrogen receptor degraders (SERDs) or known inhibitors of the PI3K pathway including PI3K inhibitors, AKT inhibitors, or mTOR inhibitors
- •Mean QT interval corrected for heart rate (QTc) ≥ 480 msec by ECG or history of familial long QT syndrome
- •Active or uncontrolled infections or serious illnesses or medical conditions
- •Clinically significant liver diseases
- •History of lung disease or history of opportunistic infections
- •Type 1 or Type 2 diabetes mellitus requiring insulin
- •Grade ≥ 2 uncontrolled hypercholesterolemia or hypertriglyceridemia
- •Known abnormalities in coagulation
- •History of hypersensitivity to the study drugs or components
- •Pregnant or lactating women
研究组 & 干预措施
Ipatasertib + Fulvestrant
干预措施: Fulvestrant (Drug)
Placebo
干预措施: Placebo (Other)
Ipatasertib + Fulvestrant
干预措施: Ipatasertib (Drug)
Placebo
干预措施: Fulvestrant (Drug)
结局指标
主要结局
Number of Participants With Progression-free Survival (PFS) Using RECIST 1.1
时间窗: 4 years
Progression-free survival (PFS) defined as time from randomization to disease progression or death from any cause, whichever occurs first. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
次要结局
- To Compare the Two Treatment Arms With Respect to Investigator Assessed PFS (Per RECIST 1.1) in the PIK3CA/AKT1/PTEN Altered Cohort(4 years)
- Commencement of Subsequent Line of Systemic Therapy or Death (TSST)(4 years)