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LBH589 Treatment for Refractory Clear Cell Renal Carcinoma

2021年10月26日 更新者：SCRI Development Innovations, LLC

A Phase II Study of LBH589 in the Treatment of Patients With Refractory Clear Cell Renal Carcinoma

Inhibition of histone deacetylase (HDAC) provides a novel approach for cancer treatment. LBH589, an oral HDAC inhibitor, has been well tolerated in phase I trials and has shown activity against several types of cancer. In this nonrandomized phase II trial, we are investigating the activity of LBH589 in the treatment of patients with refractory clear cell renal carcinoma.

研究概览

地位

完全的

条件

干预/治疗

详细说明

Inhibition of histone deacetylase (HDAC) provides a potential target for cancer treatment. Histones are components of the core proteins of nucleosomes, and acetylation and deacetylation of these proteins play a role in the regulation of gene expression. HDAC activity is known to be increased in many types of malignant cells; HDAC inhibitors have been shown to induce differentiation, cell cycle arrest, and apoptosis in cultured tumor cells. Since this tumor-associated mechanism is common to many types of cancer, HDAC may have a broad role in cancer treatment.

研究类型

介入性

注册 (实际的)

20

阶段

  • 阶段2

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

  • 美国
    • Florida
      • Fort Myers、Florida、美国、33901
        • Florida Cancer Specialists
    • Georgia
      • Gainesville、Georgia、美国、30501
        • Northeast Georgia Medical Center
    • Louisiana
      • Baton Rouge、Louisiana、美国、70806
        • Baton Rouge General Medical Center
    • Maryland
      • Bethesda、Maryland、美国、20817
        • Center for Cancer and Blood Disorders
    • Nebraska
      • Omaha、Nebraska、美国、68114
        • Methodist Cancer Center
    • New Jersey
      • Morristown、New Jersey、美国、07960
        • Hematology Oncology Associates of Northern NJ
    • Ohio
      • Cincinnati、Ohio、美国、45242
        • Oncology Hematology Care
    • Tennessee
      • Chattanooga、Tennessee、美国、37404
        • Chattanooga Oncology Hematology Associates
      • Nashville、Tennessee、美国、37023
        • Tennessee Oncology, PLLC
    • Virginia
      • Newport News、Virginia、美国、23601
        • Peninsula Cancer Institute

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 documented metastatic or locally unresectable clear cell renal carcinoma. In patients with mixed histologies, the clear cell component must comprise > 75% of the cancer.
  • Documented disease progression or intolerance while receiving treatment with: a) sunitinib, sorafenib, or both, and b) temsirolimus.
  • Maximum of 4 prior systemic regimens allowed and may include other targeted agents, immunotherapy and chemotherapy.
  • Measurable disease by RECIST criteria.
  • ECOG PS 0 or 1.
  • Laboratory values as follows: ANC >= 1500/μL, Hgb >= 9 g/dL, Platelets >= 100,000/uL, AST/SGOT and ALT/SGPT <= 2.5 x ULN or <= 5.0 x ULN in patients with liver metastases, Creatinine <= 2.0 mg/dL Or Calculated Creatinine Clearance >= 50 ml/min, Albumin >= 3 g/dL, Potassium >= lower limit normal (LLN),Phosphorous >= LLN, Calcium >= LLN, Magnesium > LLN
  • Women of childbearing potential must have a negative serum or urine pregnancy test performed within 7 days prior to start of treatment.
  • Life expectancy > 12 weeks.
  • Accessible for treatment and follow-up.
  • All patients must be able to understand the nature of the study and give written informed consent prior to study entry.

Exclusion Criteria:

  • Age < 18 years of age.
  • Prior treatment with an HDAC inhibitor.
  • Impaired cardiac function
  • Ongoing therapy with antiarrhythmics or other medications associated with QTc prolongation.
  • Uncorrected hypokalemia or hypomagnesemia.
  • Uncontrolled hypertension or cardiac arrhythmias.
  • Active parenchymal brain metastases. Patients who have had brain metastases resected, or have received radiation therapy ending > 8 weeks prior to study entry are eligible if they meet all of the following criteria: 1) residual neurologic symptoms < grade 1, 2) no dexamethasone requirement, 3) follow-up MRI shows regression of lesions after treatment, with no new lesions appearing.
  • Active meningeal metastases.
  • Known diagnosis of human immunodeficiency virus (HIV) infection.
  • Unresolved diarrhea > CTCAE grade 1.
  • Concomitant requirement for medication classified as CYP3A4 inducers or inhibitors.
  • Chemotherapy, investigational drug therapy, major surgery < 4 weeks prior to starting study drug or patients that have not recovered from side effects of previous therapy.
  • Patient is < 5 years free of another primary malignancy except if the other primary malignancy is not currently clinically significant or requiring active intervention, or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in situ. Existence of any other malignant disease is not allowed.
  • Concomitant use of any anti-cancer therapy or radiation therapy.
  • Pregnant or breast feeding or female of reproductive potential not using 2 effective methods of birth control.
  • Male patients whose sexual partners are women of childbearing potential not using effective birth control.
  • Patients with gastrointestinal (GI) tract disease, causing the inability to take oral medication, malabsorption syndrome, a requirement for intravenous (IV) alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease.
  • Other concurrent severe, uncontrolled infection or intercurrent illness
  • Abnormal thyroid function (TSH or free T4) detected at screening. Patients with known hypothyroidism who are stable on thyroid replacement are eligible.

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
其他：Treatment
LBH589 will be administered orally at a dose of 45 mg (1 - 5 mg capsule and 2 - 20 mg capsules) on Monday and Thursday of each week (twice weekly). To enable patients to undergo cardiac monitoring, all patients must begin treatment on a Monday, and continue Monday/Thursday dosing during subsequent treatment cycles. Patients with objective response or stable disease after re-evaluation at week 8 will continue LBH589 at the same dose until disease progression, unacceptable toxicity and/or at the discretion of the investigator.
药品：LBH589
LBHLBH589 will be administered orally at a dose of 45 mg (1 - 5 mg capsule and 2 - 20 mg capsules) on Monday and Thursday of each week (twice weekly). To enable patients to undergo cardiac monitoring (Section 3.5.2), all patients must begin treatment on a Monday, and continue Monday/Thursday dosing during subsequent treatment cycles.
其他名称：
  • 帕比司他

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
Progression-free Survival
大体时间：18 months
Progression-free survival was defined as the interval from the date of first treatment with panobinostat until the date that disease progression or death occurred. Progressive disease (PD): 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm.
18 months

次要结果测量

结果测量
措施说明
大体时间
Number of Participants Experiencing ≥Grade 2 Adverse Events
大体时间：18 months
An adverse event (AE) is the development of an undesirable medical condition, or the deterioration of a preexisting medical condition (other than the condition that is being treated by the trial) following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. The number of participants experiencing such adverse events that are related to the study drug are reported here.
18 months
Number of Participants With Overall Response
大体时间：18 months

Response was evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. Overall response is defined as the proportion of participants whose disease either decreased (partial response- PR) or disappeared (Complete response - CR).

Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD
18 months

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。

赞助

SCRI Development Innovations, LLC

合作者

Novartis

调查人员

  • 学习椅：John D. Hainsworth, M.D.、SCRI Development Innovations, LLC

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。

一般刊物

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1月1日

初级完成 (实际的)

2010年3月1日

研究完成 (实际的)

2010年6月1日

研究注册日期

首次提交

2007年10月26日

首先提交符合 QC 标准的

2007年10月26日

首次发布 (估计)

2007年10月29日

研究记录更新

最后更新发布 (实际的)

2021年11月23日

上次提交的符合 QC 标准的更新

2021年10月26日

最后验证

2021年10月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • SCRI GU 49

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