MC1431 Randomized Phase II Trial to Evaluate Alisertib Alone or Combined With Fulvestrant for Women With Advanced, Endocrine-Resistant Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Mayo Clinic
- 入组人数
- 96
- 试验地点
- 13
- 主要终点
- Tumor Response Rate Defined as 100% Times the Number of Patients Who Meet the Criteria for Complete Response (CR) or Partial Response (PR) Using RECIST Criteria Version 1.1
研究概览
简要总结
This phase II trial studies how well alisertib with or without fulvestrant works in treating patients with endocrine-resistant breast cancer that has spread to other places in the body. Alisertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Hormone therapy using fulvestrant may fight breast cancer by blocking the use of estrogen by the tumor cells or reducing the amount of estrogen made by the body. Giving alisertib with or without fulvestrant may be better in treating patients with breast cancer.
详细描述
PRIMARY OBJECTIVES:
I. To assess the impact on objective tumor response rate (using Response Evaluation Criteria in Solid Tumors [RECIST] criteria) with the addition of fulvestrant to alisertib in women with endocrine resistant, advanced estrogen receptor positive breast cancer.
SECONDARY OBJECTIVES:
I. To evaluate the safety profile of each treatment regimen. II. To assess the impact on median progression-free survival with the addition of fulvestrant to alisertib.
III. To obtain estimated tumor response rate and the median progression-free survival time during alisertib and fulvestrant treatment in the cohort of patients who progress during alisertib monotherapy, and crossover to receive the combination of alisertib and fulvestrant.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 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
- •PRE-REGISTRATION ELIGIBILITY
- •Post-menopausal defined as
- •Age >= 60 and amenorrhea > 12 consecutive months, OR
- •Age < 60 and amenorrhea > 12 consecutive months without another cause and documented follicle stimulating hormone (FSH) level of > 35 mIU/mL, OR
- •Previous bilateral oophorectomy
- •Histologic proof of metastatic or locally advanced, unresectable breast cancer
- •History of ER positive (+) (>= 10% of cells positive on hematoxylin and eosin stain [H&E]), HER2 negative (-) breast cancer disease, either as a
- •History of primary, operable ER+/HER2- invasive breast cancer OR
- •History of de novo metastatic breast cancer that is ER+/HER2-
- •Note: HER2- (negative) disease defined as one of the following:
- •HER2 immunohistochemistry (IHC) expression of 0, 1+ and in-situ hybridization (ISH) non-amplified
- •HER2 IHC expression of 0, 1+ and ISH not done
- •HER2 IHC expression of 2+ and ISH non-amplified
- •IHC not done and ISH non-amplified
- •Prior treatment
- •No more than two prior chemotherapy regimens in the metastatic setting
- •Prior treatment with fulvestrant in the metastatic setting is required, except for patients with a history of ER-negative metastatic breast cancer
- •Unlimited prior endocrine therapy regimens in the metastatic setting are allowed
- •No prior treatment with an aurora Kinase inhibitor (either an aurora A or pan-aurora kinase inhibitor)
- •Disease that is measurable where:
- •A non-nodal lesion is considered measurable if its longest diameter can be accurately measured as >= 2.0 cm with chest x-ray, or as >= 1.0 cm with computed tomography (CT) scan, CT component of a positron emission tomography (PET)/CT, or magnetic resonance imaging (MRI)
- •A malignant lymph node is considered measurable if its short axis is >= 1.5 cm when assessed by CT scan (CT scan slice thickness recommended to be no greater than 5 mm); Note: tumor lesions in a previously irradiated area are not considered measurable disease; Note: disease that is measurable by physical examination only is not eligible
- •No history of tumors involving spinal cord or heart
- •History of brain metastases as per the following criteria:
- •Patients with a history of resected brain metastases are eligible only if they are asymptomatic and have stable MRI scans for 3 consecutive months, including < 28 days prior to pre-registration
- •Patients who receive stereotactic radiosurgery or whole brain radiation for brain metastases are eligible only if they are asymptomatic and have stable MRI scans for 3 consecutive months, including < 28 days prior to pre-registration
- •Fully recovered from acute, reversible effects of prior therapy regardless of interval since last treatment;
- •EXCEPTION: neuropathies - if grade 2 neuropathies have been stable for at least 3 months since completion of prior treatment patient is eligible
- •Eastern Cooperative Oncology Group (ECOG) performance status: 0, 1, 2
- •Not receiving administration of proton pump inhibitor, H2 antagonist, or pancreatic enzymes
- •Willing to limit daily alcohol intake to the following: one 12-oz glass of beer, one 6-oz glass of wine, or one 1.5-oz portion of 80-proof alcohol
- •No uncontrolled intercurrent illness including, but not limited to:
- •Ongoing or active infection
- •Symptomatic congestive heart failure
- •Unstable angina pectoris
- •Uncontrolled symptomatic cardiac arrhythmia
- •Uncontrolled hypertension (defined as blood pressure > 160/90)
- •No history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen
- •No other active second malignancy other than non-melanoma skin cancers and in situ cervical cancers within 5 years of registration
- •NOTE: A second malignancy is not considered active if all treatment for that malignancy is completed and the patient has been disease-free for at least 5 years prior to registration
- •Ability to provide written informed consent
- •Willing to return to enrolling institution for follow-up during the active treatment; event monitoring following completion of therapy may occur outside the enrolling institution
- •No history of myocardial infarction =< 6 months prior to pre-registration or New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
- •No prior allogeneic bone marrow or organ transplantation
- •No known clinical finding or suspicion of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C
- •No co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
- •Able to swallow oral medication
- •No known gastrointestinal (GI) disease or GI procedures that could interfere with the oral absorption or tolerance of alisertib; examples include, but are not limited to partial gastrectomy, history of small intestine surgery, and celiac disease
- •No visceral crisis: Visceral crisis is not the mere presence of visceral metastases, but implies severe organ dysfunction as assessed by symptoms and signs, laboratory studies, and rapid progression of disease
- •No requirement for constant administration of proton pump inhibitor, H2 antagonist, or pancreatic enzymes
- 另有 11 项未显示
排除标准
- •REGISTRATION EXCLUSION CRITERIA
- •Any of the following therapies prior to registration:
- •Chemotherapy =< 21 days
- •Immunotherapy =< 21 days
- •Biologic therapy =< 21 days
- •Hormonal therapy =< 14 days
- •Monoclonal antibodies =< 14 days
- •Radiation therapy =< 14 days
- •Administration of myeloid growth factors or platelet transfusion =< 14 days prior to registration
- •Systemic infection requiring intravenous (IV) antibiotic therapy =< 14 days prior to registration
- •Treatment with clinically significant enzyme inducers, such as the enzyme-inducing antiepileptic drugs phenytoin, carbamazepine or phenobarbital, or rifampin, rifabutin, rifapentine or St. John's wort =< 14 days prior to registration
- •Receipt of corticosteroids =< 7 days prior to registration, unless patient has been taking a continuous dose of no more than 15 mg/day of prednisone for at least 30 days prior to registration
研究组 & 干预措施
Arm I (alisertib)
Patients receive alisertib PO BID on days 1-3, 8-10, and 15-17. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression, may cross-over to Arm II.
干预措施: Alisertib (Drug)
Arm II (alisertib, fulvestrant)
Patients receive fulvestrant IM over 1-2 minutes on days 1 and 15 of course 1 and on day 1 of all subsequent courses. Patients also receive alisertib PO BID on days 1-3, 8-10, and 15-17. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Alisertib (Drug)
Arm II (alisertib, fulvestrant)
Patients receive fulvestrant IM over 1-2 minutes on days 1 and 15 of course 1 and on day 1 of all subsequent courses. Patients also receive alisertib PO BID on days 1-3, 8-10, and 15-17. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Fulvestrant (Drug)
Arm I (alisertib)
Patients receive alisertib PO BID on days 1-3, 8-10, and 15-17. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression, may cross-over to Arm II.
干预措施: Laboratory Biomarker Analysis (Other)
Arm II (alisertib, fulvestrant)
Patients receive fulvestrant IM over 1-2 minutes on days 1 and 15 of course 1 and on day 1 of all subsequent courses. Patients also receive alisertib PO BID on days 1-3, 8-10, and 15-17. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
结局指标
主要结局
Tumor Response Rate Defined as 100% Times the Number of Patients Who Meet the Criteria for Complete Response (CR) or Partial Response (PR) Using RECIST Criteria Version 1.1
时间窗: Up to 4.5 years
For arm I, tumor response rate is defined as 100% times the number of patients who meet the criteria for CR or PR on 2 consecutive evaluations approximately 8 weeks apart during treatment with alisertib monotherapy divided by the number of patients who started alisertib monotherapy. For arm II, tumor response rate is defined as 100% times the number of patients who meet the criteria for CR or PR on 2 consecutive evaluations approximately 8 weeks apart during treatment with combination of alisertib and fulvestrant divided by the number of patients who started treatment with the combination of a
次要结局
- Biomarkers and ER Alpha Expression Assessed Using Tumor Tissue(Up to 4 weeks)
- Change in Blood Biomarker Levels(Baseline to 28 days)
- Change in Tumor Biomarker Levels(Baseline to 28 days)
- Clinical Benefit Rate (CBR) During Initial Treatment Defined as Percentage of Patients Who Completed 6 Courses of Treatment Without Documentation of Disease Progression(At 24 weeks)
- Duration of Response Defined as Time From Randomization to Disease Progression Among Those Patients Whose Disease Meets the RECIST Criteria for CR or PR on 2 Consecutive Evaluations Approximately 8 Weeks Apart During Initial Treatment(Up to about 5 years)
- Incidence of Adverse Events Graded by Common Terminology Criteria-Criteria for Adverse Events (CTCAE) Version 4.0(Up to 30 days after last administration of study drug)
- Overall Survival(Up to 5 years)
- Progression-free Survival(Time from randomization to the first of these disease events: local/regional or distant breast recurrence, DCIS or invasive breast disease in contralateral breast, non-breast second primary, or death due to any cause, assessed up to 5 years)
- Incidence of Grade 4 Adverse Events Graded by Common Terminology Criteria-Criteria for Adverse Events (CTCAE) Version 4.0(Up to 30 days after last administration of study drug)