A Pilot Preoperative Trial of Ganetespib With Paclitaxel for Triple-Negative Breast Cancer
试验速览
- 阶段
- 不适用
- 状态
- 撤回
- 主要终点
- Change in GR protein
研究概览
简要总结
Based on preclinical data implicating GR, AR, and JAK/STAT activation as potent mechanisms of breast cancer cell survival despite chemotherapy administration (i.e. chemotherapy resistance), the study will test a novel approach for improving chemotherapy effectiveness by adding Hsp90 inhibition to antagonize the anti-apoptotic signaling pathways that are initiated via GR, AR, and JAK/STAT activation.
详细描述
STUDY OBJECTIVES
Primary:
• To determine tumor GR, AR, JAK and other Hsp90 client protein expression before and after two weeks of ganetespib monotherapy
Secondary:
- To determine the pathological Complete Response (pCR) rate associated with weekly treatment of ganetespib plus paclitaxel followed by the combination treatment of doxorubicin plus cyclophosphamide
- To characterize the toxicity of study 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
- Female
- 接受健康志愿者
- 否
入选标准
- •Invasive carcinoma of the breast
- •ER negative and PR negative tumors defined as < 1% of tumor nuclei that are immunoreactive for ER and PR
- •HER2 non-overexpressing status documented as:
- •FISH ratio of less than 2.0, OR
- •IHC staining of 0 or 1+
- •No evidence of distant metastatic disease. Patients with regional lymph node involvement are eligible.
- •>18 years old
- •No prior treatment for the disease under study
- •No prior treatment within 5 years for any other cancer including chemotherapy, surgery (except for diagnostic biopsy), radiotherapy, hormonal therapy, or investigational agents, unless curative treatment of non-melanoma skin-cancer or in-situ cancer
- •Able to understand and sign an informed consent (or have a legal representative who is able to do so)
- •Clinically or radiologically measureable disease in the breast after diagnostic biopsy, defined as longest diameter greater than or equal to 2cm
- •Willing to undergo three mandatory core biopsies after diagnosis to obtain tissue for biologic expression profiling.
- •An Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1
- •Adequate bone marrow reserves as evidenced by:
- •Leukocytes > 3,000/μL
- •Absolute neutrophil count (ANC) > 1,500/μL without the use of hematopoietic growth factors,
- •Platelet count > 100,000/μL, and
- •Hemoglobin > 9 g/dL
- •Adequate hepatic function as evidenced by:
- •Serum total bilirubin within institutional normal limits
- •Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase less than or equal to 2.5 × ULN
- •Adequate renal function as evidenced by a serum creatinine within ULN or creatinine clearance > 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
- •Eligible for treatment with paclitaxel, doxorubicin and cyclophosphamide
- •If of childbearing potential, are willing to abstain from sexual intercourse or to use an effective form of contraception (e.g., a double-barrier method) during the study and for 90 days following the last dose of ganetespib
排除标准
- •• Patients may not be receiving any other investigational agents.
- •Patients may not have a known hypersensitivity to any of the components of ganetespib
- •Patients may not have a history of severe allergic reactions to paclitaxel or other drugs formulated in Cremaphor® EL.
- •Patients with a QTc > 470 ms, a family history of long QT Syndrome, and those on medications known to cause Torsades de Pointes will be excluded from the study.
- •Patients may not have an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Patients may not have New York Heart Association (NYHA) Class III or IV congestive heart failure or left ventricular ejection fraction (LVEF) < 50%.
- •As patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study.
- •Patients may not have a need for chronic systemic steroid therapy
- •Patients may not be pregnant or breastfeeding
研究组 & 干预措施
Therapy
Patients will receive ganetespib monotherapy for two weeks followed by twelve weeks of ganetespib/paclitaxel therapy followed by 4 bi-weekly doses of doxorubicin/cyclophosphamide therapy followed by surgery.
干预措施: Ganetespib (Drug)
Therapy
Patients will receive ganetespib monotherapy for two weeks followed by twelve weeks of ganetespib/paclitaxel therapy followed by 4 bi-weekly doses of doxorubicin/cyclophosphamide therapy followed by surgery.
干预措施: Paclitaxel (Drug)
Therapy
Patients will receive ganetespib monotherapy for two weeks followed by twelve weeks of ganetespib/paclitaxel therapy followed by 4 bi-weekly doses of doxorubicin/cyclophosphamide therapy followed by surgery.
干预措施: Doxorubicin (Drug)
Therapy
Patients will receive ganetespib monotherapy for two weeks followed by twelve weeks of ganetespib/paclitaxel therapy followed by 4 bi-weekly doses of doxorubicin/cyclophosphamide therapy followed by surgery.
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
Change in GR protein
时间窗: 2 weeks
次要结局
- Pathological Complete Response (pCR) rate(6 month)
- Ganetespib toxicity(14 weeks)