Phase II Study of Ixabepilone and Cyclophosphamide as Neoadjuvant Therapy in HER2-Negative Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 168
- 试验地点
- 20
- 主要终点
- Pathologic Complete Response Rate (pCR)
研究概览
简要总结
We propose to evaluate ixabepilone in combination with cyclophosphamide for the neoadjuvant treatment of locally advanced breast cancer. In this regimen, ixabepilone is substituted for docetaxel, since preclinical and clinical
studies suggest that ixabepilone is more active than either docetaxel or paclitaxel. The combination of ixabepilone and cyclophosphamide could further improve the efficacy of non-anthracycline neoadjuvant therapy.
详细描述
In this study, patients with early stage, HER2-negative breast cancer will receive neoadjuvant treatment with ixabepilone and cyclophosphamide given every three weeks for a total of six cycles. Following surgery patients with hormone receptor-positive tumors will receive anti-estrogen treatment. Patients may receive local regional radiation therapy after surgery per institutional guidelines at the investigator's discretion. Baseline tumor tissue and tumor tissue removed at the time of surgery will be tested by Oncotype Detailed Description (DX) assay to determine whether it is predictive of response to this neoadjuvant treatment regimen. This study will be one of the first investigations of the combination of ixabepilone and cyclophosphamide as neoadjuvant treatment for HER2-negative breast cancer. It will examine this treatment regimen for potential advantages gained from substitution of ixabepilone for a taxane and use of non-anthracycline agents.
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
- •Female patients, age ≥18 years.
- •Histologically confirmed invasive adenocarcinoma of the breast.
- •Primary palpable disease confined to a breast and axilla on
- •physical examination. For patients without clinically suspicious
- •axillary adenopathy, the primary tumor must be larger than 2 cm
- •in diameter by physical exam or imaging studies (clinical T2-T3,
- •N0-N1, M0). For patients with clinically suspicious axillary
- •adenopathy, the primary breast tumor can be any size (clinical
- •T1-3, N1-2, M0). (T1N0M0 lesions are excluded.)
- •Patients without clearly defined palpable breast mass or axillary
- •lymph nodes but radiographically measurable tumor masses are
- •acceptable. Accepted procedures for measuring breast disease
- •are mammography, MRI, and breast ultrasound. This will need to
- •be re-evaluated after 3 cycles and prior to surgery.
- •Eastern Cooperative Oncology Group performance status (ECOG
- •No metastatic disease, as documented by complete staging workup
- •6 weeks prior to initiation of study treatment.
- •No previous treatment for breast cancer.
- •HER2-negative tumor status. HER2-negative is defined as:
- •Immunohistochemical (IHC) 0, IHC 1+ OR
- •IHC 2+ or IHC 3+ must be confirmed as FISH (fluorescence in situ
- •hybridization) negative (defined by ratio <2.2).
- •Adequate hematologic function with:
- •Absolute neutrophil count (ANC) >1500/μL.
- •Platelets ≥100,000/μL.
- •Hemoglobin ≥10 g/dL.
- •Adequate hepatic function with:
- •Serum bilirubin ≤ the institutional upper limit of normal (ULN).
- •Aspartate aminotransferase (AST) ≤2.5 x institutional ULN.
- •Alanine aminotransferase (ALT) ≤2.5 x institutional ULN.
- •Adequate renal function with serum creatinine ≤1.5 x ULN.
- •Estrogen and progesterone receptor status in the primary tumor
- •known or pending at the time of study registration.
- •Knowledge of the investigational nature of the study and ability to
- •provide consent for study participation.
- •For patients who had, or will have sentinel lymph node and/or
- •axillary dissection prior to initiation of study treatment, completion
- •at least 4 weeks prior to starting study treatment and well-healed
- •Bilateral, synchronous breast cancer is allowed if one primary
- •tumor meets the inclusion criteria.
- •Sufficient archived breast tumor specimen available at baseline
- •for the Oncotype DX assay.
排除标准
- •Inflammatory breast cancer.
- •Peripheral neuropathy (motor or sensory) ≥ grade 1 by the
- •Common Terminology Criteria for Adverse Events version 3.0
- •(CTCAE v 3.0).
- •Prior radiation that included ≥30% of major bone marrow containing
- •areas (pelvis, lumbar, spine).
- •Chronic use of cytochrome P450 (CYP) 3A4 inhibitors and use of
- •the following strong CYP3A4 inhibitors: ketoconazole,
- •itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir,
- •telithromycin, ritonavir, amprenavir, indinavir, nelfinavir,
- •delavirdine, and voriconazole. Use of these agents should be
- •discontinued at least 72 hours prior to initiation of study treatment.
- •Chemotherapy within 5 years of starting study treatment except
- •for low doses of agents used for anti-inflammatory indications
- •such as rheumatoid arthritis, psoriasis, and connective tissue
- •disorders. Although such doses and schedules cannot result in
- •myelosuppression, patients must discontinue this therapy while
- •they are receiving study treatment.
- •Known or suspected hypersensitivity to Cremophor®EL
- •(polyoxyethylated castor oil) or a drug formulated in
- •Cremophor®EL such as paclitaxel, or any other agent given in the
- •course of this study.
- •Pregnancy or breast-feeding. A negative serum pregnancy test
- •within 7 days prior to first study treatment (Day 1, Cycle 1) for all
- •women of childbearing potential is required. Patients of
- •childbearing potential must agree to use a birth control method
- •that is approved by their study physician while receiving study
- •treatment and for 3 weeks after their last dose of study treatment.
- •Patients must agree to not breast-feed while receiving study
- •Concurrent treatment with an ovarian hormonal replacement
- •therapy or with hormonal agents such as raloxifene, tamoxifen or
- •other selective estrogen receptor modulator (SERM). Patients
- •must have discontinued use of such agents prior to beginning
- •study treatment.
- •History of malignancy treated with curative intent within the
- •previous 5 years with the exception of skin cancer, cervical
- •carcinoma in situ, or follicular thyroid cancer. Patients with
- •previous invasive cancers (including breast cancer) are eligible if
- •the treatment was completed more than 5 years prior to initiating
- •current study treatment, and there is no evidence of recurrent
- •Uncontrolled intercurrent illness including (but not limited to)
- •ongoing or active infection.
- •Chronic treatment with corticosteroid unless treatment was begun
- •>6 months prior to study treatment and is at a low dose (≤20 mg
- •methylprednisolone or equivalent).
- •Use of any investigational agent within 30 days of administration
- •of the first dose of study drug.
- •Requirement for radiation therapy concurrent with neoadjuvant
- •study chemotherapy.
- •Concurrent treatment with any anti-cancer therapy other than
- 另有 13 项未显示
研究组 & 干预措施
Ixabepilone/Cyclophosphamide
Systemic Therapy followed by surgery and possible radiation therapy
干预措施: Ixabepilone (Drug)
Ixabepilone/Cyclophosphamide
Systemic Therapy followed by surgery and possible radiation therapy
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
Pathologic Complete Response Rate (pCR)
时间窗: 6 months
Pathologic complete response (pCR) rate will be determined by the pathologic evaluation of breast and lymph node samples collected at the time of surgery. pCR is defined as no residual disease in breast or lymph nodes in resected tissue samples.
次要结局
- Disease Free Survival(36 Months)
- Absence of Grade-4 Non-hematologic Toxicity Excluding, Alopecia, Nausea, Vomiting and Bone Pain(3 months)
- Overall Survival(36 months)