A Phase Ib/II Study of Cisplatin, Paclitaxel, and RAD001 in Patients With Metastatic Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 55
- 试验地点
- 4
- 主要终点
- Maximum Feasible Dose in Milligrams Per Meter Squared of Body Surface Area (mg/m2) of Cisplatin and Paclitaxel for Women With Metastatic Breast Cancer
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy, such as cisplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving cisplatin and paclitaxel together with everolimus may kill more tumor cells.
PURPOSE: This phase I/II trial is studying the side effects of giving cisplatin and paclitaxel together with everolimus and to see how well it works in treating patients with metastatic breast cancer.
详细描述
OBJECTIVES:
Primary
- Safety profile of cisplatin, paclitaxel, and everolimus (RAD001) in patients with metastatic breast cancer. (Phase I)
- Progression-free survival (Phase II)
Secondary
- Overall response rate
- Time to progression
- Number of patients with worst-grade toxicities Tertiary
- To determine p53, p63, p73, and phosphatase and tensin homolog (PTEN) levels by immunohistochemistry (IHC).
- To screen for exon 9 (E542K and E545K), exon 20 (H1047R), and phosphatidylinositol 3-kinase (PI3K) (p110α) mutations in DNA extracted from paraffin blocks.
- To correlate IHC results with clinical outcome and with the different subtypes of breast cancer determined by molecular classification (basal-type vs luminal A vs luminal B) based on microarrays of RNA extracted from formalin-fixed paraffin-embedded blocks.
- To generate microarrays of RNA extracted from fresh-frozen core biopsies (when available) to identify a pretreatment gene signature that mirrors the established p63 and p73 gene signatures that predict response to treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Treatment
干预措施: cisplatin (Drug)
Treatment
干预措施: everolimus (Drug)
Treatment
干预措施: paclitaxel (Drug)
Treatment
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Maximum Feasible Dose in Milligrams Per Meter Squared of Body Surface Area (mg/m2) of Cisplatin and Paclitaxel for Women With Metastatic Breast Cancer
时间窗: at 8 weeks
The recommended dose for the Phase II trial will be the most prevalent dose delivered per week in Phase I that allows for safe and feasible administration of the medications.The maximum tolerated dose (MTD) is defined as the dose preceding that at which 2 or more of 3 patients experience dose-limiting toxicity (DLT) during the initial cycle of therapy. DLTs include Common Toxicity Criteria (CTC) Grade 4 neutropenia (absolute neutrophil count \[ANC\] \< 0.5 x 10 9/L for \> 5 days), febrile neutropenia (ANC \< 1.0 x 10 0/L with fever \> 38.5 degrees Centigrade) or documented infection associated with Grade 3-4 neutropenia, CTC Grade 4 thrombocytopenia \< 25 x 10 9/L or CTC Grade 3 \< 50-25 x 10 9/L thrombocytopenia with bleeding, and Grade 3-4 non-hematologic toxicity despite symptomatic therapy.
Patients With Progression-free Survival
时间窗: at 6 months
Patients who had not experienced disease progression and who were alive at 6 months after study entry
Maximum Feasible Dose in mg of RAD001 (Everolimus)for Women With Metastatic Breast Cancer
时间窗: at 8 weeks
The recommended dose for the Phase II trial will be the most prevalent dose delivered per day in Phase I that allows for safe and feasible administration the medication. The MTD is defined as the dose preceding that at which 2 or more of 3 patients experience dose-limiting toxicity (DLT) during the initial cycle of therapy. DLTs include Common Toxicity Criteria (CTC) Grade 4 neutropenia (absolute neutrophil count \[ANC\] \< 0.5 x 10 9/L for \> 5 days), febrile neutropenia (ANC \< 1.0 x 10 0/L with fever \> 38.5 degrees Centigrade) or documented infection associated with Grade 3-4 neutropenia, CTC Grade 4 thrombocytopenia \< 25 x 10 9/L or CTC Grade 3 \< 50-25 x 10 9/L thrombocytopenia with bleeding, and Grade 3-4 non-hematologic toxicity despite symptomatic therapy
次要结局
- Time to Progression(Up to 64 weeks)
- Patients With Overall Response(every 12 weeks)
- Time to Progression in Patients With Metastatic Basal-like Breast Cancer.(Up to 64 weeks)
研究者
Ingrid Mayer, MD
Assistant Professor of Medicine; Clinical Director, Breast Cancer Program
Vanderbilt-Ingram Cancer Center