A Phase II Randomized Trial of the Combination of Ridaforolimus and Exemestane, Compared to Ridaforolimus, Dalotuzumab and Exemestane in High Proliferation, Estrogen Receptor Positive Breast Cancer Patients
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 80
- 主要终点
- 1. Progression-free Survival (PFS) According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Based on Blinded Independent Central Review (BICR)
研究概览
简要总结
The purpose of the study is to evaluate the efficacy of the triplet of ridaforolimus, dalotuzumab and exemestane compared to the combination of ridaforolimus and exemestane in post-menopausal participants with breast cancer. The primary hypothesis of the study is that the triplet of ridaforolimus, dalotuzumab and exemestane will improve progression free survival (PFS) compared to ridaforolimus and exemestane.
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
- •Females with a histologically confirmed diagnosis of breast cancer that is metastatic or locally advanced (locally advanced tumors must not be amenable to
- •surgery or radiation therapy with curative intent) with the following pathological characteristics determined locally: estrogen receptor positive and Human Epidermal Growth Factor Receptor 2 (HER-2) negative, and Ki67 (a tumor marker) ≥ 15% determined by the central study laboratory
- •Post-menopausal
- •With advanced breast cancer whose disease was refractory to previous letrozole or anastrozole
- •Has at least one confirmed measurable metastatic lesion
- •Has a performance status ≤ 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
- •Has a life expectancy of at least 3 months
- •Adequate organ function
排除标准
- •Is receiving any other concurrent systemic tumor therapy, including
- •hormonal agents and HER-2 inhibitors
- •Previously received rapamycin or rapamycin analogs, including
- •ridaforolimus, temsirolimus, or everolimus
- •Received prior treatment with Insulin-like Growth Factor 1 Receptor (IGF-1R) inhibitors, Phosphatidylinositol 3-Kinase (PI3K) inhibitors, or
- •other experimental agents that target PI3K, Protein Kinase B (AKT), or Mammalian Target of Rapamycin (mTOR) pathway
- •Is receiving chronic corticosteroids administered at doses greater than
- •those used for normal replacement therapy
- •Has active brain metastasis or leptomeningeal carcinomatosis; patients
- •with adequately treated brain metastases are eligible if they meet certain criteria
- •Known allergy to macrolide antibiotics
- •Has an active infection requiring antibiotics
- •Significant or uncontrolled cardiovascular disease
- •Poorly controlled Type 1 or 2 diabetes
- •Is known to be Human Immunodeficiency Virus (HIV) positive
- •Has a known history of active hepatitis B or C. Healthy carriers of hepatitis B are not allowed on this study
研究组 & 干预措施
Ridaforolimus + Dalotuzumab + Exemestane
Participants receive ridaforolimus 10 mg orally (PO) every 5 days (QD x 5) plus dalotuzumab 10 mg/kg intravenously (IV) every week (QW) plus exemestane 25 mg PO every day (QD) in 28-day cycles until documented disease progression or unacceptable toxicity.
干预措施: Ridaforolimus (Drug)
Ridaforolimus + Dalotuzumab + Exemestane
Participants receive ridaforolimus 10 mg orally (PO) every 5 days (QD x 5) plus dalotuzumab 10 mg/kg intravenously (IV) every week (QW) plus exemestane 25 mg PO every day (QD) in 28-day cycles until documented disease progression or unacceptable toxicity.
干预措施: Dalotuzumab (Drug)
Ridaforolimus + Dalotuzumab + Exemestane
Participants receive ridaforolimus 10 mg orally (PO) every 5 days (QD x 5) plus dalotuzumab 10 mg/kg intravenously (IV) every week (QW) plus exemestane 25 mg PO every day (QD) in 28-day cycles until documented disease progression or unacceptable toxicity.
干预措施: Exemestane (Drug)
Ridaforolimus + Exemestane
Participants receive ridaforolimus 30 mg PO QD x 5 plus exemestane 25 mg PO QD treatment in 28-day cycles until documented disease progression or unacceptable toxicity.
干预措施: Ridaforolimus (Drug)
Ridaforolimus + Exemestane
Participants receive ridaforolimus 30 mg PO QD x 5 plus exemestane 25 mg PO QD treatment in 28-day cycles until documented disease progression or unacceptable toxicity.
干预措施: Exemestane (Drug)
结局指标
主要结局
1. Progression-free Survival (PFS) According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Based on Blinded Independent Central Review (BICR)
时间窗: From Day 1 through last post-study efficacy follow-up (up to ~19 months)
PFS was defined as the time from randomization to progressive disease, or death, whichever occurs first. Response was assessed according to RECIST 1.1 by BICR. According to RECIST 1.1, progressive disease (PD) was defined as a 20% relative increase in the sum of diameters (SOD) of target lesions, taking as reference the nadir SOD and an absolute increase of \>5 mm in the SOD, or the appearance of new lesions. PFS was analyzed using the Kaplan-Meier method and median PFS (95% confidence interval \[CI\]) in weeks was reported for each treatment arm. Per protocol, participants remained on assigned treatment until disease progression. Participants who discontinued study treatment for reasons other than disease progression continued to be assessed by imaging until objective documentation of progression. All participants (including participants who discontinued study treatment) were followed for survival until investigator notification to discontinue.
次要结局
- Percent Change From Baseline in Sum of Target Lesion Diameters at Week 16(Baseline, Week 16)
- 3. Percentage of Participants With Objective Response (Objective Response Rate [ORR]) According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Based on Blinded Independent Central Review (BICR).(From Day 1 through last post-study efficacy follow-up (up to ~19 months))
- Overall Survival (OS)(From Day 1 through last post-study efficacy follow-up (up to ~19 months))