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Everolimus and Gefitinib in Treating Patients With Progressive Glioblastoma Multiforme or Progressive Metastatic Prostate Cancer

2015年12月15日 更新者:Memorial Sloan Kettering Cancer Center

A Phase I/II Trial to Assess the Tolerability of RAD 001 With Gefitinib in Patients With Glioblastoma Multiforme and Prostate Cancer and Efficacy in Patients With Castrate Metastatic Prostate Cancer

RATIONALE: Everolimus may stop the growth of tumor cells by stopping blood flow to the tumor. Gefitinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Combining everolimus with gefitinib may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of everolimus when given together with gefitinib and to see how well they work in treating patients with progressive glioblastoma multiforme or (progressive metastatic prostate cancer closed to accrual 10/19/06).

研究概览

详细说明

OBJECTIVES:

Primary

  • Determine the maximum tolerated dose of everolimus when given in combination with gefitinib in patients with progressive glioblastoma multiforme or (progressive castrate metastatic prostate cancer -closed to accrual as of 10/19/2006). (Phase I)
  • Determine the safety and efficacy of this regimen in patients with progressive glioblastoma multiforme or (progressive castrate metastatic prostate cancer - closed to accrual as of 10/19/2006). (Phase II)

Secondary

  • Determine whether a pharmacokinetic interaction exists between everolimus and gefitinib in patients treated with this regimen.
  • Determine the association between clinical outcomes and markers that may predict sensitivity of a tumor in patients treated with this regimen.
  • Determine the pharmacodynamic effects of this regimen on post-therapy tumor specimens and peripheral blood mononuclear cells from these patients.

OUTLINE: This is a phase I, open-label, non-randomized, dose-escalation study of everolimus followed by a phase II study.

  • Phase I: Patients receive oral everolimus on day 1 and oral gefitinib once daily on days 8-21. Beginning on day 22, patients receive oral everolimus once weekly and oral gefitinib once daily. Treatment with the combination continues in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of everolimus until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

  • Phase II (prostate cancer patients only) (closed to accrual as of 10/19/2006): Patients receive oral everolimus (at the MTD determined in phase I) once weekly and oral gefitinib once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.

研究类型

介入性

注册 (实际的)

61

阶段

  • 阶段2
  • 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

    • New York
      • New York、New York、美国、10065
        • Memorial Sloan Kettering Cancer Center
      • Barcelona、西班牙、08035
        • Vall d'Hebron University Hospital

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 至 120年 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

男性

描述

DISEASE CHARACTERISTICS:

  • Histologically confirmed diagnosis of 1 of the following:

    • Glioblastoma multiforme (GBM) (phase I only)

      • Progressive disease despite standard therapy
      • Progressive disease based on 1 of the following:

        • New or progressive (25% bidimensional increase) soft tissue masses on CT scan or MRI
        • New or prior lesions that have increased in size by physical examination
      • Patients who had prior interstitial brachytherapy or stereotactic radiosurgery must have confirmation of true disease progression (rather than radiation necrosis) by positron-emission tomography scan, thallium scanning, magnetic resonance spectroscopy, or surgical documentation
    • Castrate metastatic prostate cancer (closed to accrual as of 10/19/2006) (phase I and II)

      • Progressive disease despite standard therapy AND castrate levels < 50 ng/dL of testosterone
      • Progressive disease based on 1 or more of the following:

        • A minimum of 3 rising levels of prostate-specific antigen (PSA) that are obtained 1 or more weeks apart OR 2 rising PSA values obtained more than 1 month apart with at least a 25% increase over the range of values
        • New or progressive (25% bidimensional increase) soft tissue masses on CT scan or MRI
        • New metastatic lesions
      • Patients on an antiandrogen as part of initial therapy must show disease progression after discontinuation of the antiandrogen
      • Patients who have not undergone surgical orchiectomy must continue with medical therapy (e.g., gonadotropin-releasing hormone analogs) to maintain castrate levels of serum testosterone
  • No brain metastases

PATIENT CHARACTERISTICS:

Age

  • Over 18

Performance status

  • Karnofsky 70-100%

Life expectancy

  • More than 3 months

Hematopoietic

  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • WBC ≥ 3,000/mm^3

Hepatic

  • ALT and AST ≤ 2.5 times upper limit of normal (ULN)
  • Bilirubin ≤ 1.5 mg/dL

Renal

  • Creatinine within 1.5 times ULN (< 1.95 mg/dL at MSKCC)

Cardiovascular

  • No significant cardiovascular disease
  • No congestive heart failure
  • No New York Heart Association class III or IV cardiac disease
  • No active angina pectoris
  • No myocardial infarction within the past 6 months

Other

  • Not pregnant
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No serious medical illness
  • No severe infection
  • No severe malnutrition
  • No other active malignancy except non-melanoma skin cancer

    • Patients are not considered to have an active malignancy if they have completed prior therapy and currently have a < 30% risk for relapse

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No concurrent biological therapy
  • No concurrent immunotherapy

Chemotherapy

  • No concurrent chemotherapy

Endocrine therapy

  • See Disease Characteristics

Radiotherapy

  • See Disease Characteristics
  • More than 4 weeks since prior radiotherapy
  • No concurrent radiotherapy

Surgery

  • See Disease Characteristics
  • Prior recent resection of recurrent or progressive GBM allowed provided patient has recovered
  • More than 4 weeks since prior major surgery

Other

  • Recovered from all prior therapy
  • More than 4 weeks since prior investigational anticancer drugs
  • No concurrent anticonvulsant that interacts with CYP3A4 (e.g., phenytoin, carbamazepine, or phenobarbital)
  • No other concurrent cytotoxic therapy
  • No other concurrent investigational or commercial agents or therapies for the malignancy

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
实验性的:Everolimus (RAD-001) and Gefitinib

•Phase I: Patients receive oral everolimus on day 1 and oral gefitinib once daily on days 8-21. Beginning on day 22, patients receive oral everolimus once weekly and oral gefitinib once daily. Treatment with the combination continues in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of everolimus until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

•Phase II (prostate cancer patients only) (closed to accrual as of 10/19/2006): Patients receive oral everolimus (at the MTD determined in phase I) once weekly and oral gefitinib once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.

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 Objective Response
大体时间:2 years
Response will be evaluated in this study using the new international criteria Response Evaluation Criteria in Solid Tumors (RECIST)
2 years

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:Lauren E. Abrey, MD、Memorial Sloan Kettering Cancer Center
  • 首席研究员:Howard I. Scher, MD、Memorial Sloan Kettering Cancer Center
  • 首席研究员:Neal Rosen, MD、Memorial Sloan Kettering Cancer Center

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

2004年3月1日

初级完成 (实际的)

2008年2月1日

研究完成 (实际的)

2008年2月1日

研究注册日期

首次提交

2004年6月10日

首先提交符合 QC 标准的

2004年6月10日

首次发布 (估计)

2004年6月11日

研究记录更新

最后更新发布 (估计)

2016年1月20日

上次提交的符合 QC 标准的更新

2015年12月15日

最后验证

2015年12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.

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