AUY922 With Lapatinib and Letrozole for ER+ HER2+ Advanced Breast Cancer
A Phase I/ II, Multi-center, Open-label Study, to Evaluate the Efficacy of AUY922 in Combination With Lapatinib With Letrozole in Postmenopausal Patients With Locally Advanced or Metastatic ER+ , HER2 + Breast Cancer
研究概览
详细说明
The dose and schedule of AUY922 is the MTD dose identified in the phase I, given as 1 hour infusion weekly.
The Phase II component will have a 2 stage design single arm design. (Section 9.0). Overall response rate (ORR) is the primary endpoint. Estimated N=40 (12 in first stage) .A total of 39 response-evaluable participants is required. In the first stage, 12 response-evaluable participants will be accrued; if there are 3 or fewer CR+PRs, the study will stop for futility. There is a 55% probability of stopping early if, in fact, the ORR is 28%. If there are 4 or more CR+PRs, the study will proceed to the second stage and an additional 27 response-evaluable participants will be accrued. We will accrue 1 additional patient (then the needed 39 to account for attrition)
研究类型
阶段
- 阶段2
- 阶段1
参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Age 18 years
- Able to sign Informed Consent
- Patients must have the following laboratory values:
Absolute Neutrophil Count (ANC) 1.5x109/L Hemoglobin (Hgb) 9 g/dl Platelets (plt) 100x109/L
- Potassium within normal limits
- Total calcium (corrected for serum albumin) and Phosphorus within normal limits
- Magnesium above LLN or correctable with supplements
- AST/SGOT and ALT/SGPT ≤ 1.5 x Upper Limit of Normal (ULN) if AP > 2.5 ULN
- AST/SGOT and ALT/SGPT ≤ 2.5 x Upper Limit of Normal (ULN) if AP ≤ 5.0 x ULN if
- Serum bilirubin 1.5 x ULN
- Serum creatinin 1.5 x ULN or 24-hour clearance 50 ml/min
- Negative serum pregnancy test. The serum pregnancy test must be obtained prior to the first administration of AUY922 (≤ 72 hours prior to dosing) in all pre-menopausal women and women <2 years after the onset of menopause
- Histologically confirmed HER2 + and ER+ or PR + (i.e., HR+) Postmenopausal women with Metastatic breast cancer or resistant locally advanced breast cancer.
- Stage of disease (stage IIIb/c not responding or progressing to standard therapy with trastuzumab) or stage IV receiving first line treatment in the metastatic setting . All patients should have documented clinical progression prior to entering study
- Prior chemotherapy for metastatic stage IV disease is prohibited for patients enrolled in phase II, but allowed up to 3 lines for patients enrolled in Phase I. Prior neoadjuvant/adjuvant chemotherapy, antiestrogens, and radiotherapy are allowed. Adjuvant hormonal therapy including aromatase inhibitors are permitted in the adjuvant, neoadjuvant or metastatic setting if discontinued at least two weeks prior to starting study treatment. Trastuzumab is permitted in the adjuvant, neoadjuvant or metastatic setting if discontinued at least 4 weeks prior to study treatment
- Patients must have at least one measurable lesion as defined by RECIST. Irradiated lesions and non-measurable disease are only evaluable for disease progression
- Patients must have tumors that carry HER-2 gene amplifications as determined by (i) fluorescence in situ hybridization (FISH) or (ii) overexpression of HER-2 protein 3+ level assessed by immunohistochemistry. Patients who have previously been treated with trastuzumab must be off treatment at least 6 weeks prior to starting study treatment.
- World Health Organization (WHO) Performance Status of < 1
- Life expectancy of > 12 weeks
Exclusion Criteria:
- Unresolved diarrhea ≥ CTCAE (v4.02) grade 1
- Pregnant or lactating women
- Impaired cardiac function, including any one of the following:
- History (or family history) of long QT syndrome
- Mean QTc ≥ 450 msec on baseline ECG
- History of clinically manifested ischemic heart disease ≤ 6 months prior to study start or History of heart failure or left ventricular (LV) dysfunction (LVEF ≤ 45%) by MUGA or ECHO or arrythmia
- Patients known to be HIV positive. Testing is not required in the absence of clinical signs and symptoms suggesting HIV infection.
- Known hypersensitivity to any of the study drugs or their excipients
- Participation in another clinical study within 30 days before first study treatment
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:不适用
- 介入模型:单组作业
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
---|---|
实验性的:AUY922
Single Arm
|
AUY 922 is given intravenously weekly; letrozole and lapatinib are given orally
其他名称:
|
研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Overall Response Rate
大体时间:2 years
|
noted by tumor response using RECIST criteria
|
2 years
|
合作者和调查者
调查人员
- 首席研究员:Zeina Nahleh, M.D.、Texas Tech University Health Sciences Center, El Paso
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.
AUY922的临床试验
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Novartis Pharmaceuticals完全的
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Novartis Pharmaceuticals完全的胃肿瘤 食管肿瘤 转移性胃癌 突变的PI3KCA蛋白 过表达的HER2蛋白台湾, 瑞士, 大韩民国, 德国, 美国, 日本
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Dale Shepard, MD, PhDNational Cancer Institute (NCI)终止
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Novartis Pharmaceuticals完全的
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University Health Network, TorontoNovartis Pharmaceuticals终止