A Randomized Phase II Pilot Study to Evaluate Safety and Efficacy of the Addition of Vismodegib to Standard Neoadjuvant Chemotherapy in Triple Negative Breast Cancer Patients
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Number of patients with treatment-related adverse events as assessed by CTCAE v4.0
研究概览
简要总结
To evaluate safety and efficacy of vismodegib with standard neoadjuvant chemotherapy in breast cancer patients based on the CTCAE v4 2010
- To study changes in biomarkers involved in the Hedgehog (HH) pathway in the first biopsy as compared to the later one
- To detect predictive factors among patients who reached pathological complete response (pCR) as compared to those with no pCR
- To evaluate the role of the addition of vismodegib in the pCR rate
- To evaluate clinical responses by breast MRI and rates of breast conservative surgery after neoadjuvant chemotherapy
- To evaluate QOL with EORTC QLQ-C30 scale
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 75 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Ability to give informed agreement and to carry out the whole study protocol during the study period
- •The patient should be able to carry out the needs of the clinical trial and have measurable disease
- •The patient should be 18-75 year-old
- •Triple negative breast cancer (ER<1%, Progesteron Receptor (PR)<1%, non-overexpressing HER2).
- •Patients with oligometastatic disease (1-2 resectable metastases) could be included
- •No previous systemic therapies
- •Patients who are going to benefit from neoadjuvant chemotherapy
- •Eastern Cooperative Oncology Group (ECOG)<2 or Karnofsky≥70%
- •Blood tests and biochemistry suitable: (absolute neutrophil count> 1500/uL; haemoglobin>9 gr/dL; platelets>100000/uL (microliters); total bilirubin≤ 1.5 the upper normal limit; GOT and GPT (transaminases)≤twice the upper normal limit; fasting glucose≤150 gr/dL; HbA1c≤8%, serum creatinine≤2 mg/dL.
排除标准
- •Severe diseases or infectious diseases or liver, kidney or bone marrow failure that advise not to participate in the study according to investigator criteria
- •Pregnancy or breast feeding period or fertility women who are not agree with contraception methods
- •Other primary tumors except for breast in situ carcinoma (CIS), cervical neoplasia(CIN) or localized skin tumors
- •Inflammatory breast cancer or bilateral breast cancer
- •Bone fractures, peptic ulcus or healing disorders
- •Any local or systemic therapy for breast cancer
- •To be maintained on immunosuppressants (prednisone > 10 mgr daily or others), aspirin> 325 mgr per day or clopidogrel > 75 mgr daily
- •Cardiomyopathy by New York Heart Association (NYHA) class II-IV; heart stroke in the previous 6 months; uncontrolled blood pressure (systolic > 150 mm Hg and /or diastolic > 100 mm Hg), coagulopathy or hemorrhagic diseases
- •Previous lung diseases
- •Personal history of abdominal perforation, abdominal abscess, or abdominal fistula.
- •Inability to swallow pills
- •Intolerance to galactose, malabsorption to galactose or/and glucose, or primary hypolactasia
研究组 & 干预措施
vismodegib plus chemotherapy
Vismodegib 150 mg orally during paclitaxel and then dose dense epirubicin + cyclophosphamide (EC) therapy (see active comparator arm)
干预措施: vismodegib (Drug)
vismodegib plus chemotherapy
Vismodegib 150 mg orally during paclitaxel and then dose dense epirubicin + cyclophosphamide (EC) therapy (see active comparator arm)
干预措施: Paclitaxel (Drug)
vismodegib plus chemotherapy
Vismodegib 150 mg orally during paclitaxel and then dose dense epirubicin + cyclophosphamide (EC) therapy (see active comparator arm)
干预措施: Epirubicin (Drug)
vismodegib plus chemotherapy
Vismodegib 150 mg orally during paclitaxel and then dose dense epirubicin + cyclophosphamide (EC) therapy (see active comparator arm)
干预措施: Cyclophosphamide (Drug)
chemotherapy
Paclitaxel 80 mg/m2 weekly on days 1, 8 and 15 each 21 days x 12 doses and then dose dense E (90 mg/m2) plus cyclophosphamide (CPA) 600 mg/m2 each 2 weeks x 4 doses
干预措施: Paclitaxel (Drug)
chemotherapy
Paclitaxel 80 mg/m2 weekly on days 1, 8 and 15 each 21 days x 12 doses and then dose dense E (90 mg/m2) plus cyclophosphamide (CPA) 600 mg/m2 each 2 weeks x 4 doses
干预措施: Epirubicin (Drug)
chemotherapy
Paclitaxel 80 mg/m2 weekly on days 1, 8 and 15 each 21 days x 12 doses and then dose dense E (90 mg/m2) plus cyclophosphamide (CPA) 600 mg/m2 each 2 weeks x 4 doses
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
Number of patients with treatment-related adverse events as assessed by CTCAE v4.0
时间窗: 21 months
次要结局
- Molecular changes in breast(30 months)
- Pathologic complete response (pCR)(30 months)
- Clinical complete response (cCR)(21 months)
- European Organisation for Research and Treatment of Cancer Quality of Life questionnaire C30 (EORTC QOL-C30)(30 months)