Phase I/II Trial of Sorafenib Plus Ixabepilone in HER2-Negative Metastatic Breast Cancer (MBC)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 83
- 试验地点
- 15
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
In this study, patients with metastatic HER2-negative breast cancer will receive treatment with ixabepilone and sorafenib until disease progression or unacceptable toxicity occurs. The Phase I portion of this study will determine the maximum tolerated doses (MTDs) of sorafenib and ixabepilone that may be used in combination for first- or second-line treatment of MBC. The MTDs identified in the Phase I portion of the study will be used in the Phase II portion which will evaluate the efficacy and safety of the combination of sorafenib and ixabepilone in patients who have received at least one prior chemotherapy treatment in either the adjuvant or neoadjuvant setting or following one prior MBC chemotherapy in MBC patients who had not received prior adjuvant or neoadjuvant breast cancer chemotherapy. This will be one of the initial trials investigating the use of this treatment combination for MBC.
This trial will be conducted under the leadership of the Sarah Cannon Research Institute (SCRI) Oncology Research Consortium, a community-based, multi-center, clinical trial organization.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Age ≥ 18 years.
- •Histologically or cytologically confirmed breast cancer diagnosis
- •with metastatic disease. Patients without pathologic or cytologic
- •confirmation of metastatic disease should have unequivocal
- •evidence of metastasis.
- •Measurable disease, as per RECIST criteria (Therasse et al.
- •. Measurable disease cannot be previously irradiated
- •unless progression was documented. Measurable disease is
- •defined as: at least one lesion that can be accurately measured in
- •at least one dimension [longest diameter to be recorded] as
- •>20 mm with conventional techniques, or as >10 mm with spiral
- •computed tomography (CT) scan. Disease must be measurable,
- •i.e., bone-only disease or evaluable-only disease is not eligible.
- •Patients with brain metastasis may participate if they:
- •have undergone appropriate treatment,
- •are at least 1 month post-treatment,
- •have no neurologic symptoms,
- •are not on steroids,
- •have a follow-up magnetic resonance imaging (MRI) scan that
- •demonstrates no residual active lesions, and
- •have no new untreated lesions.
- •5 The following prior therapies are allowed:
- •No prior chemotherapy in the metastatic setting. However,
- •patients must have received prior adjuvant or neo-adjuvant
- •chemotherapy.
- •Prior radiation therapy in either the metastatic or early-stage
- •setting, as long as <25% of the bone marrow has been
- •treated. Radiation therapy must be completed at least
- •14 days prior to study registration, and all radiation-related
- •toxicities must be resolved to ≤ grade 1 before the patient is
- •eligible for study inclusion.
- •Any number of hormonal therapies in the neo-adjuvant,
- •adjuvant, or metastatic setting is allowed. Patients must
- •discontinue hormonal therapy at least 1 week prior to starting
- •study treatment.
- •Prior bevacizumab administered >4 weeks before initiation of
- •study treatment is allowed.
- •6 HER2-negative status. Documentation of HER2 results must be
- •available at the time of study enrollment. HER2-negative is
- •defined as:
- •Immunohistochemical (IHC) 0 or IHC 1+ OR
- •Fluorescence in situ hybridization (FISH) negative (defined by
- •FISH ratio <2.2) OR
- •Silver in-situ hybridization (SISH) negative (defined by SISH
- •ratio <2.2).
- •Patients with an IHC 2+ will need to be validated as HER2-negative
- •7 An Eastern Cooperative Oncology Group (ECOG) performance
- •status of < or = to
- •Normal bone marrow function as defined by:
- •absolute neutrophil count (ANC) >1,500/μL;
- 另有 91 项未显示
排除标准
- 未提供
研究组 & 干预措施
Dose Level 1
Sorafenib PO BID (200mg), Ixabepilone IV every 21 days (40mg/m^2)
干预措施: Sorafenib (Drug)
Dose Level 1
Sorafenib PO BID (200mg), Ixabepilone IV every 21 days (40mg/m^2)
干预措施: Ixabepilone (Drug)
Dose Level -1
Sorafenib PO BID (200mg), Ixabepilone IV every 21 days (32mg/m^2)
干预措施: Sorafenib (Drug)
Dose Level -1
Sorafenib PO BID (200mg), Ixabepilone IV every 21 days (32mg/m^2)
干预措施: Ixabepilone (Drug)
Dose Level 1a
Sorafenib PO BID (400mg), Ixabepilone IV every 21 days (32mg/m^2)
干预措施: Sorafenib (Drug)
Dose Level 1a
Sorafenib PO BID (400mg), Ixabepilone IV every 21 days (32mg/m^2)
干预措施: Ixabepilone (Drug)
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: every 9 weeks until treatment discontinuation or death on study
Measured from Day 1 of study drug administration to disease progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) - progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
次要结局
- 6-month Progression-Free Survival(every 9 weeks, up to 6 months)
- Objective Response Rate(every 9 weeks until discontinuation of treatment)
- Overall Survival (OS)(every 9 weeks until treatment discontinuation or death on study)
- Number of Patients With Adverse Events as a Measure of of Safety and Tolerability(every 9 weeks until treatment discontinuation or unacceptable toxicity)