A Randomized Phase II Trial of Tamoxifen Versus Z-Endoxifen HCL in Postmenopausal Women With Metastatic Estrogen Receptor Positive, HER2 Negative Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 81
- 试验地点
- 1,083
- 主要终点
- Progression Free Survival (PFS)
研究概览
简要总结
This randomized phase II trial studies how well tamoxifen citrate works compared with z-endoxifen hydrochloride in treating patients with breast cancer that has spread to nearby tissue or lymph nodes or other parts of the body and has estrogen receptors but not human epidermal growth factor receptor 2 (HER2) receptors on the surface of its cells. Estrogen can cause the growth of tumor cells. Hormone therapy using tamoxifen citrate or z-endoxifen hydrochloride may fight breast cancer by lowering the amount of estrogen the body makes. It is not yet known whether tamoxifen citrate or z-endoxifen hydrochloride is more effective in treating patients with breast cancer.
详细描述
PRIMARY OBJECTIVES:
I. To assess whether progression-free survival with z-endoxifen hydrochloride (HCl) relative to that with tamoxifen (tamoxifen citrate) is prolonged in postmenopausal women with local advanced or metastatic estrogen receptor (ER) positive/Her2 negative breast cancer.
SECONDARY OBJECTIVES:
I. To assess the safety profile of each of these agents in this patient population.
II. To assess whether the tumor response rate (as determined using the Response Evaluation Criteria in Solid Tumors [RECIST] criteria) among those randomized to z-endoxifen HCl differs from that among those randomized to tamoxifen.
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 CRITERIA
- •Women who agree to undergo a standard of care core biopsy of recurrent or metastatic breast cancer to confirm the ER+ (>= 10% nuclear staining) and HER2 negative status
- •Patient must have been previously treated with an aromatase inhibitor (either letrozole, anastrozole or exemestane) either in the adjuvant or metastatic setting, and have one of the following types of primary or secondary endocrine resistant disease
- •Primary clinical resistance is defined as one of the following:
- •Recurrence within the first 2 years of adjuvant endocrine therapy while on aromatase inhibitor therapy
- •Progression within first 6 months of initiating first-line endocrine therapy (either aromatase inhibitor or fulvestrant containing regimen) for the treatment of metastatic breast cancer
- •Secondary clinical resistance is defined as one of the following:
- •Recurrence after year 2 while receiving adjuvant aromatase inhibitor therapy, or within 12 months of completing adjuvant aromatase inhibitor therapy
- •Progression occurring 6 or more months after initiating the first endocrine therapy for metastatic disease (either fulvestrant or aromatase inhibitor containing regimen)
- •Patients with a history of measurable disease as defined by RECIST criteria or bone only disease are eligible; Note: those patients with non-measurable disease and bone metastases are eligible
- •No history of tumors involving spinal cord or heart
- •No current evidence of visceral crisis or lymphangitic spread
- •No known brain metastases
- •Women must be postmenopausal
- •Postmenopausal status is verified by:
- •Prior bilateral surgical oophorectomy, or
- •Age >= 60 years, or
- •Age < 60 with no menses for > 1 year with follicle-stimulating hormone (FSH) and estradiol levels within post menopausal range, according to institutional standard
- •Prior treatment
- •No more than two prior chemotherapy regimens in the metastatic setting
- •Prior treatment with an aromatase inhibitor (either anastrozole, letrozole or exemestane), either in the adjuvant or metastatic setting is required
- •Unlimited prior endocrine regimens in the metastatic setting, which may have included an everolimus or cyclin dependent kinase (CDK) 4/6 inhibitor (such as palbociclib, abemaciclib or ribociclib) containing regimen
- •Prior tamoxifen treatment is allowed in the adjuvant setting, but patients must not have experienced relapse within 1 year of stopping tamoxifen
- •No prior treatment with tamoxifen in the metastatic setting
- •No prior treatment with endoxifen
- •Patients who have not fully recovered from acute, reversible effects of prior therapy regardless of interval since last treatment are not eligible to participate in this study
- •EXCEPTION: neuropathies-if grade 2 neuropathies have been stable for at least 3 months since completion of prior treatment patient is eligible
- •Not receiving any medications or substances that are strong inhibitors of cytochrome P450 family 2, subfamily D, polypeptide 6 (CYP2D6)
- •Not receiving any other investigational agents
- •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)
- •None of the following co-morbid conditions:
- •Cataracts of grade 2 or greater as per Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
- •Retinopathy of grade 2 or greater as per CTCAE version 4.0
- •Note: patients that have cataracts that do not require surgery are eligible
- •Note: serious adverse events will be reported on CTEP-Adverse Event Reporting System (AERS) using CTCAE version (v)5.0
- •Deep vein thrombosis/pulmonary embolism (DVT/PE) within the past 6 months
- •Note: patients that are on anticoagulant therapy for maintenance are eligible as long as the DVT and/or PE occurred > 6 months prior to enrollment, and there is no evidence for active thrombosis (either DVT or PE)
- •No other active second malignancy other than non-melanoma skin cancers within 3 years of pre-registration; 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 3 years prior to pre-registration
- •Eastern Cooperative Oncology Group (ECOG) performance status: 0-2
- •Able to swallow oral formulation of the study agent
- •Hemoglobin >= 9 g/dL
- •Platelet count >= 75,000/mm^3
- •Creatinine =< 1.5 x upper limits of normal (ULN)
- •Total bilirubin =< 1.5 x upper limits of normal (ULN)
- •Aspartate aminotransferase (AST) =< 2.5 x upper limits of normal (ULN); for patients with liver metastasis: =< 5 x upper limits of normal (ULN)
- 另有 22 项未显示
排除标准
- 未提供
研究组 & 干预措施
Arm I (z-endoxifen hydrochloride)
Patients receive z-endoxifen hydrochloride PO on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: Endoxifen Hydrochloride (Drug)
Arm I (z-endoxifen hydrochloride)
Patients receive z-endoxifen hydrochloride PO on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Arm II (tamoxifen citrate)
Patients receive tamoxifen citrate PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression and bone metastases may cross over to Arm I and receive z-endoxifen hydrochloride starting no later than 28 days after documentation of disease progression.
干预措施: Pharmacological Study (Other)
Arm I (z-endoxifen hydrochloride)
Patients receive z-endoxifen hydrochloride PO on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: Pharmacological Study (Other)
Arm II (tamoxifen citrate)
Patients receive tamoxifen citrate PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression and bone metastases may cross over to Arm I and receive z-endoxifen hydrochloride starting no later than 28 days after documentation of disease progression.
干预措施: Laboratory Biomarker Analysis (Other)
Arm II (tamoxifen citrate)
Patients receive tamoxifen citrate PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression and bone metastases may cross over to Arm I and receive z-endoxifen hydrochloride starting no later than 28 days after documentation of disease progression.
干预措施: Tamoxifen Citrate (Drug)
结局指标
主要结局
Progression Free Survival (PFS)
时间窗: Assessed up to 5 years
The primary endpoint is progression-free survival (PFS) defined as the time from randomization to documentation of local, regional or distant disease progression or death without progression of disease.
次要结局
- Incidence of Adverse Events, Per Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0(Up to 5 years)
- Tumor Response Rate by Study Arm, Defined as the Number of Patients With a Complete or Partial Response(Up to 5 years)
- Overall Survival Distribution by Study Arm(The time from registration to death due to any cause, assessed up to 5 years)