Phase I Study of LBH589 & Erlotinib for Advanced Aerodigestive Tract Cancers
2015年2月3日 更新者:H. Lee Moffitt Cancer Center and Research Institute
Phase I Study of LBH589 in Combination With Erlotinib for Advanced Aerodigestive Tract Cancers (CLBH5889CUS11T)
The main purpose of the study is to:
- Determine the safety and tolerability of erlotinib and LBH589B.
- Establish a recommended phase II expansion dosing of LBH589B and erlotinib in patients with advanced aerodigestive tract cancers.
研究概览
研究类型
介入性
注册 (实际的)
44
阶段
- 阶段1
联系人和位置
本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。
学习地点
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Florida
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Tampa、Florida、美国、33612
- H. Lee Moffitt Cancer Center & Research Institute
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参与标准
研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 及以上 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
描述
Inclusion Criteria:
- Histologically or cytologically documented diagnosis of advanced/metastatic NSCLC or Head and Neck cancer.
- Male or female patients aged ≥ 18 years old
- Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed
- Have progressive and measurable disease that can be measured by Response Evaluation Criteria in Solid Tumors (RECIST) criteria
- Patients must have discontinued prior systemic chemotherapy by 14 days.
Patients must meet the following laboratory criteria:
- Serum albumin ≥ 3g/dL
- Aspartic transaminase (AST/SGOT) and alanine transaminase (ALT/SGPT) ≤ 2.5 x upper limit of normal (ULN)or ≤ 5.0 x ULN if the transaminase elevation is due to leukemic involvement
- Serum bilirubin ≤ 1.5 x ULN
- Serum creatinine ≤ 1.5 x ULN or 24-hour creatinine clearance ≥ 50 ml/min
- Serum potassium ≥ lower limit of normal (LLN) and ≤ ULN
- Serum phosphorous ≥ LLN
- Serum total calcium (corrected for serum albumin) or serum ionized calcium ≥ LLN
- Serum magnesium ≥ LLN
- Absolute neutrophil count (ANC) (ANC: segmented and bands) ≥ 1.5 X10^9/L
- Platelets ≥ 100 X 10^9/L
- Baseline multiple gated acquisition imaging (MUGA) or echocardiogram (ECHO) must demonstrate left ventricular ejection fraction (LVEF) ≥ the lower limit of the institutional normal
- Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1
- Reproductive potential must be either terminated (by surgery, radiation, or menopause) or attenuated by the use of an approved contraceptive method during and for 3 to 6 months following the study.
- Patient instructed that intravenous (IV) bisphosphonates will be withheld for the first 8 weeks of LBH589 therapy due to risk of hypocalcemia.
Exclusion Criteria:
Impaired cardiac function including any one of the following:
- Screening electrocardiogram (ECG) with a corrected QT (QTc) > 450 msec confirmed by central laboratory prior to enrollment to the study
- Patients with congenital long QT syndrome
- History of sustained ventricular tachycardia
- Any history of ventricular fibrillation or torsades de pointes
- Bradycardia defined as heart rate < 50 beats per minute. Patients with a pacemaker and heart rate ≥ 50 beats per minute are eligible.
- Patients with a myocardial infarction or unstable angina within 6 months of study entry
- Congestive heart failure - New York Heart Association (NYHA) class III or IV
- Right bundle branch block and left anterior hemiblock (bifascicular block)
- Patients with a history of uncontrolled or chronic atrial fibrillation.
- Uncontrolled hypertension, blood pressure (BP) >180/110 on 3 separate occasions despite oral antihypertensive medications
- Concomitant use of drugs with a risk of causing torsades de pointes Concomitant use of CYP3A4 inhibitors
- Patients with documented central nervous system or leptomeningeal metastasis (brain metastasis) at the time of study entry. Patients with prior brain metastasis may be considered if they have completed their treatment for brain metastasis, no longer require corticosteroids, and are asymptomatic.
- Patients with unresolved diarrhea > Common Terminology Criteria for Adverse Events (CTCAE) grade 1
- Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral LBH589
- Other concurrent severe and/or uncontrolled medical conditions
- Patients who have received chemotherapy < 14 days, any investigational drug < 14 days or undergone major surgery < 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy.
- Concomitant use of any anti-cancer therapy (except erlotinib) or radiation therapy.
- Female patients who are pregnant or breast feeding or patients of reproductive potential not using two effective methods of birth control. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days of the first administration of oral LBH589
- Male patients whose sexual partners are WOCBP not using effective birth control
- Patients with known positivity for human immunodeficiency virus (HIV) or hepatitis C; baseline testing for HIV and hepatitis C is not required
- Patients with any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent
- Patients who are not willing to refrain from wearing contact lenses during study participation will be excluded.
学习计划
本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。
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 |
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实验性的:Dose Escalation Followed by Expansion
Eligible participants were enrolled in a 3+3 dose-escalation design to determine the maximum tolerated dose (MTD) of twice weekly panobinostat plus daily erlotinib at 4 planned dose levels (DLs).
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Panobinostat was taken twice weekly, for 2 out of 3 weeks of each cycle.
Each cycle was defined as a 21-day period.
Four dose levels of panobinostat in combination with erlotinib were planned: 1) dose level 1 (DL1) = panobinostat 20 mg by mouth (PO) twice weekly for 2 out of 3 weeks + erlotinib 100 mg PO daily; 2) dose level 2 (DL2) = panobinostat 30 mg and erlotinib 100 mg; 3) dose level 3 (DL3) = panobinostat 30 mg and erlotinib 150 mg; and 4) dose level 4 (DL4) = panobinostat 40 mg and erlotinib 150 mg.
Doses were not escalated over the course of treatment of an individual participant.
其他名称:
Erlotinib was taken daily without interruption.
Each cycle was defined as a 21-day period.
Panobinostat was taken twice weekly, for 2 out of 3 weeks of each cycle.
Four dose levels of panobinostat in combination with erlotinib were planned: 1) dose level 1 (DL1) = panobinostat 20 mg by mouth (PO) twice weekly for 2 out of 3 weeks + erlotinib 100 mg PO daily; 2) dose level 2 (DL2) = panobinostat 30 mg and erlotinib 100 mg; 3) dose level 3 (DL3) = panobinostat 30 mg and erlotinib 150 mg; and 4) dose level 4 (DL4) = panobinostat 40 mg and erlotinib 150 mg.
Doses were not escalated over the course of treatment of an individual participant.
其他名称:
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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 |
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Maximum Tolerated Dose (MTD)
大体时间:4 Months
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Determine safety and tolerability of erlotinib and LBH589B and establish a recommended phase II expansion dosing of LBH589B and erlotinib in patients with advanced aerodigestive tract cancers.
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4 Months
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
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Disease Control Rate (DCR)
大体时间:Up to 48 months
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DCR: The percentage of patients with advanced or metastatic cancer who have achieved complete response (CR), partial response (PR) and stable disease (SD) to a therapeutic intervention in clinical trials of anticancer agents.
CR: is defined as disappearance of all target lesions.
PR: is defined as at least a 30% decrease in the sum of longest diameter (LD) of target lesions taking as reference the baseline sum LD.
SD: is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum LD since the treatment started.
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Up to 48 months
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Progression Free Survival (PFS) by Cancer Type
大体时间:Up to 48 months
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Progressive Disease (PD) is defined as at least a 20% increase in the sum of LD of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
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Up to 48 months
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Overall Survival (OS) by Cancer Type
大体时间:Up to 48 months
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Overall survival (OS) is the duration from date of randomization to date of death from any cause.
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Up to 48 months
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合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
调查人员
- 首席研究员:Jhanelle Gray, M.D.、H. Lee Moffitt Cancer Center and Research Institute
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始
2008年11月1日
初级完成 (实际的)
2013年8月1日
研究完成 (实际的)
2015年2月1日
研究注册日期
首次提交
2008年8月18日
首先提交符合 QC 标准的
2008年8月18日
首次发布 (估计)
2008年8月20日
研究记录更新
最后更新发布 (估计)
2015年2月4日
上次提交的符合 QC 标准的更新
2015年2月3日
最后验证
2015年2月1日
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.
Panobinostat (LBH589)的临床试验
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Sidney Kimmel Cancer Center at Thomas Jefferson...Novartis终止
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City of Hope Medical CenterNational Cancer Institute (NCI)完全的
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Mayo ClinicNational Cancer Institute (NCI)完全的粘膜相关淋巴组织结外边缘区B细胞淋巴瘤 | 淋巴结边缘区 B 细胞淋巴瘤 | 复发性成人伯基特淋巴瘤 | 复发性成人弥漫性大细胞淋巴瘤 | 复发性成人淋巴母细胞淋巴瘤 | 复发性 1 级滤泡性淋巴瘤 | 复发性 2 级滤泡性淋巴瘤 | 复发性 3 级滤泡性淋巴瘤 | 复发性套细胞淋巴瘤 | 脾边缘区淋巴瘤 | 华氏巨球蛋白血症 | 外周T细胞淋巴瘤 | 间变性大细胞淋巴瘤 | 血管免疫母细胞性T细胞淋巴瘤 | 成人鼻型结外 NK/T 细胞淋巴瘤 | 肝脾T细胞淋巴瘤 | 移植后淋巴增生性疾病 | 复发性成人 T 细胞白血病/淋巴瘤 | 复发性蕈样肉芽肿/Sezary 综合征 | 复发性小淋巴细胞淋巴瘤 | 小肠淋巴瘤美国
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Radboud University Medical Center完全的
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Mayo ClinicNational Cancer Institute (NCI)完全的粘膜相关淋巴组织结外边缘区B细胞淋巴瘤 | 淋巴结边缘区 B 细胞淋巴瘤 | 复发性成人伯基特淋巴瘤 | 复发性成人弥漫性大细胞淋巴瘤 | 复发性成人淋巴母细胞淋巴瘤 | 复发性 1 级滤泡性淋巴瘤 | 复发性 2 级滤泡性淋巴瘤 | 复发性 3 级滤泡性淋巴瘤 | 复发性套细胞淋巴瘤 | 复发性边缘区淋巴瘤 | 脾边缘区淋巴瘤 | 华氏巨球蛋白血症 | 间变性大细胞淋巴瘤 | 血管免疫母细胞性T细胞淋巴瘤 | 成人鼻型结外 NK/T 细胞淋巴瘤 | 肝脾T细胞淋巴瘤 | 移植后淋巴增生性疾病 | 复发性成人急性淋巴细胞白血病 | 复发性成人霍奇金淋巴瘤 | 复发性成人 T 细胞白血病/淋巴瘤 | 复发性皮肤 T 细胞非霍奇金淋巴瘤 | 复发性蕈样肉芽肿/Sezary 综合征 | 复发性小淋巴细胞淋巴瘤 | 难... 及其他条件美国
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Novartis Pharmaceuticals完全的
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Novartis Pharmaceuticals完全的
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H. Lee Moffitt Cancer Center and Research InstituteNovartis Pharmaceuticals完全的