A Phase I/II Study of BEZ235 in Patients With Advanced Solid Malignancies Enriched by Patients With Advanced Breast Cancer
A Phase I/II, Multi-center, Open-label Study of BEZ235, Administered Orally on a Continuous Daily Dosing Schedule in Adult Patients With Advanced Solid Malignancies Including Patients With Advanced Breast Cancer
This is a first-in-human, phase I/Ib clinical research study with BEZ235, an inhibitor of phosphatidylinositol 3'-kinase (PI3K). The study consists of a dose escalation part followed by a safety dose expansion part:
Dose escalation part (advanced solid tumors, including patients with breast cancer being treated with trastuzumab):
Patients receive oral BEZ235 once daily on days 1-28 of the first course. Courses will repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of at least 3 patients receive escalating doses of BEZ235, as single agent or in combination with trastuzumab, until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose expected to produce during the first course of treatment dose-limiting toxicity in 33% of patients.
Once the MTD has been defined, the safety expansion parts of the trial will be opened for enrollment.
Safety dose expansion part (advanced solid tumors, including patients with breast cancer being treated with trastuzumab):
Patients will be treated with BEZ235, as single agent or in combination with trastuzumab, given at the MTD, once daily. Treatment of patients will continue until disease progression or occurrence of unacceptable side effects.
研究概览
研究类型
注册 (实际的)
阶段
- 阶段1
联系人和位置
学习地点
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Essen、德国、45147
- Novartis Investigative Site
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California
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Los Angeles、California、美国、90095
- University of California at Los Angeles JonssonComprehensiveCancerCtr
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Connecticut
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New Haven、Connecticut、美国、06520
- Yale University School of Medicine YaleCancerCtr-ClinTrialsOffice
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Massachusetts
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Boston、Massachusetts、美国、02215
- Dana Farber Cancer Institute Clinical Trials ProjectManager
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Nevada
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Las Vegas、Nevada、美国、89135
- Nevada Cancer Institute NVCC - Huntsman
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South Carolina
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Greenville、South Carolina、美国、29605
- Cancer Centers of the Carolinas CCC Faris
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Tennessee
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Nashville、Tennessee、美国、37203
- Sarah Cannon Research Institute Dept.ofSarahCannonCancerCtr(2)
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Texas
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Dallas、Texas、美国、75246
- Baylor Health Care System/Sammons Cancer Center Baylor- Sammons
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Houston、Texas、美国、77030-4009
- University of Texas/MD Anderson Cancer Center Thoractic Head/Neck Med.Onc(2)
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Tyler、Texas、美国、75702
- Tyler Cancer Center TCC
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Manchester、英国、M20 9BX
- Novartis Investigative Site
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Amsterdam、荷兰、1066 CX
- Novartis Investigative Site
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Catalunya
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Barcelona、Catalunya、西班牙、08035
- Novartis Investigative Site
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Comunidad Valenciana
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Valencia、Comunidad Valenciana、西班牙、46010
- Novartis Investigative Site
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Valencia、Comunidad Valenciana、西班牙、46009
- Novartis Investigative Site
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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:
[Single agent dose escalation arm]: Patients with histologically-confirmed, advanced unresectable solid tumors including CS patients who have progressed on (or not been able to tolerate) standard therapy within three months before screening visit or for whom no standard anticancer therapy exists.
[Combination part]: Patients with metastatic HER2+ Breast Cancer, after failure of trastuzumab treatment. Eligible patients will have to have tumors carrying molecular alterations of PIK3CA and/or PTEN.
[Single agent safety expansion arm]: Patients with histologically-confirmed, advanced unresectable solid tumors including CS patients who have progressed on (or not been able to tolerate) standard therapy within three months before screening visit or for whom no standard anticancer therapy exists. Patients will be prescreened for molecular alterations affecting PIK3CA and/or PTEN. Patients with NSCLC will also be pre-screened for EGFR mutation.
Exclusion Criteria:
- Patients who have brain metastases, which are progressive and/or requiring medical intervention for symptom control
- Prior treatment with a PI3K inhibitor
- Acute or chronic liver disease or renal disease
- Acute or chronic pancreatitis
- Patients with unresolved diarrhea ≥ CTCAE grade 2
- Impaired cardiac function or clinically significant cardiac diseases
- Patients with diabetes mellitus requiring insulin treatment
- Patients with known coagulopathies
- Patients with a history of photosensitivity reactions to other drugs
- Any of the following ophthalmological findings:
- Progressive eye disease that could lead to severe loss of visual acuity or visual field
- loss during the study period
- Inability to perform the ophthalmic procedures required in this protocol
- Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol.
Other protocol-defined inclusion/exclusion criteria may apply
学习计划
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：非随机化
- 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 |
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实验性的：BEZ235 Alone, Dose Escalation
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实验性的：BEZ235 + trastuzumab, Dose Escalation
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实验性的：BEZ235 Alone, MTD Expansion
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实验性的：BEZ235 + Trastuzumab, MTD Expansion
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研究衡量的是什么？
主要结果指标
结果测量 |
大体时间 |
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determine the maximum Tolerated Dose (MTD) of BEZ235 as single agent and in combination with trastuzumab (Dose escalation part)
大体时间：at end of study
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at end of study
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assess the safety & tolerability of BEZ235 SDS as single agent and in combination with trastuzumab administered to patients at the MTD level (Safety expansion part)
大体时间：at end of study
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at end of study
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次要结果测量
结果测量 |
大体时间 |
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assess the safety and tolerability of the various formulations of BEZ235
大体时间：at end of study
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at end of study
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Asses the Pharmacokinetics of BEZ235 which includes AUC, Cmax, Tmax, t1/2 as endpoints
大体时间：at end of study
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at end of study
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Preliminary anti-tumor activity (tumor response) of BEZ235 SDS as single agent and in combination with trastuzumab
大体时间：end of study
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end of study
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合作者和调查者
出版物和有用的链接
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.
BEZ235的临床试验
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Cliniques universitaires Saint-Luc- Université...Novartis终止
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Novartis Pharmaceuticals撤销
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Goethe University完全的
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Pfizer完全的