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Radiation Therapy (IMRT) + RAD001 (Everolimus) + Cisplatin for Patients With Head and Neck Cancer

2013年7月23日 更新者:Memorial Sloan Kettering Cancer Center

A Phase I Study of Radiation Therapy (IMRT) + RAD001 (Everolimus) + Cisplatin for Patients With Head and Neck Cancer

The purpose of this study is to determine the best doses of RAD001 (everolimus) tablets and cisplatin to give to patients who are receiving radiation therapy for head and neck cancer.

研究概览

研究类型

介入性

注册 (实际的)

13

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

    • New York
      • New York、New York、美国、10065
        • Memorial Sloan-Kettering Cancer Center

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:

  • Pathologically confirmed head and neck carcinoma, any histology (other than sarcoma, lymphoma, or melanoma). Patients with thyroid cancer (papillary, follicular, undifferentiated, Hurthle cell, medullary, or anaplastic) may be eligible.
  • Patients with cutaneous squamous cell cancer or basal cell cancer arising in the head and neck may be eligible.
  • Patients will have either Stage III- IVB unresected disease (Patients with stage II-IV B hypopharynx cancer and patients with Stage IIB - IVB nasopharynx cancer may also be eligible) OR
  • Will be status post macroscopically complete resection of disease with one of the following poor risk features in the surgical pathology specimen:

Malignant involvement of 2 or more regional lymph nodes Extracapsular extension of nodal disease Microscopically involved mucosal margins of resection T3 or T4 pathologic stage (excluding T3N0 laryngeal squamous cell cancer) Perineural involvement Oral cavity or oropharyngeal primaries with nodal disease at levels IV or V

  • Age > or = to 18 years
  • Karnofsky performance status > or = to 70%
  • Adequate bone marrow function: Absolute neutrophil count > than or = to 1.5 X 109/L, Platelets > or = to 100 x 109/L, Hemoglobin > 10 g/dL.
  • Adequate liver function: serum bilirubin < or = to 1.5 X upper limit of normal(ULN), and serum transaminases (alanine aminotransferase, ALT; aspartate aminotransferase, AST) activity < or = to 2.0 X ULN.
  • Adequate renal function: serum creatinine within institutional normal limits, or calculated creatinine clearance (by Cockcroft and Gault method) > or = to 45 mL/min for patients with creatinine limits above institutional normal.
  • INR < 1.5 or aPTT < 1.5 X upper limits of normal
  • For women of child-bearing potential, negative urine or serum pregnancy test within 14 days prior to administration of RAD001.
  • Men and women of childbearing potential must be willing to consent to using effective birth control methods while on treatment and for at least 3 months there after.
  • The planned radiation therapy treatment dose must meet protocol requirements (Resected tumors/post-operative patients: maximum planned dose 66 Gy. Unresected tumors: maximum planned dose 70 Gy).

Exclusion Criteria:

  • Any prior radiation therapy for head and neck cancer. Any prior radiation therapy to >25% of the bone marrow. Any prior radiation to whole pelvis and/or brain.
  • Patients with unresected squamous cell cancer (SCC) arising in the oral cavity, oropharynx, larynx, or hypopharynx are excluded, unless they at have received at least 2 cycles of induction chemotherapy with a regimen that includes cisplatin or carboplatin. (For patients with unresected head and neck tumors other than SCC of oral cavity, oropharynx, larynx, or hypopharynx, there is no requirement for induction chemotherapy prior to protocol chemoradiation)..
  • Therapeutic anticoagulation with coumadin (warfarin)
  • Peripheral neuropathy > or = to grade 3, according to Common Terminology Criteria for Adverse Events (CTCAE), version 3.0.
  • Hypertriglyceridemia > or = to grade 2 (CTCAE version 3.0).
  • Patients who require chronic treatment with steroids ( > prednisone 5 mg/day) or other immunosuppressive agents are excluded. Both cisplatin and RAD001 are immunosuppressive, and chronic steroid use (> prednisone 5 mg/day) or use of other immunosuppressive agents might increase the risk of lethal infection in this setting. Patients on low- dose steroid replacement regimens (< or = to prednisone 5 mg/day) are not excluded, because low dose steroids should not be immunosuppressive.
  • Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection).
  • Active infection or serious underlying medical condition that would impair the patient's ability to receive protocol treatment. Other concurrent severe and/or uncontrolled medical disease which would compromise participation in the study in the opinion of the investigator (e.g., uncontrolled diabetes, unstable angina, or congestive heart failure - New York Heart Association Class III or IV)
  • HIV-positive patients. These patients are at increased risk of lethal infections when treated with marrow suppressive therapy. Additionally, pharmacokinetic interactions between antiretroviral therapy and the study regimen may be problematic for these patients.
  • Women who are pregnant or lactating
  • Other active malignancy, other than indolent malignancies which the investigator determines are unlikely to interfere with treatment and safety analysis. For example, patients with nonmelanoma skin cancer, in situ carcinoma of the cervix, or prostate cancer with no current biochemical (PSA) or radiologic evidence of disease may enroll.
  • Impaired lung function: O2 saturation 88% or less at rest on room air by Pulse Oximetry. If O2 saturation is < or = to 88% at rest, further pulmonary function tests (PFTs) should be ordered to confirm normal pulmonary function and eligibility.
  • Patients should not receive immunization with attenuated live vaccines within one week of study entry or during the study period. Close contact with those who have received attenuated live vaccines should be avoided during treatment with everolimus. Examples of live vaccines include intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella, and TY21a typhoid vaccines.
  • Liver disease such as cirrhosis or severe hepatic impairment (Childs-Pugh class C).

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:Chemoradiation
  • IMRT, 1 fraction/day, over approximately 33 treatment days
  • RAD001 per oral or PEG, per dose escalation scheme (Days 1 - 42)
  • Cisplatin IV weekly, per dose escalation scheme (Days 1, 8, 15, 22, 29, 36)

All patients will receive standard treatment with definitive radiation therapy (IMRT, intensity modulated radiation therapy), administered as one fraction per day (Monday through Friday) over approximately 33 fractions. Patients with resected tumors will be treated to a maximum dose of 66 Gy. Patients with unresected tumors will be treated to a maximum dose of 70 Gy.

Patients will receive daily RAD0001 it will be administered orally or via percutaneous gastrostomy tube (PEG) once daily according to the dose escalation scheme plus cisplatin intravenously once per week (Days 1, 8, 15, 22, 29, 36) according to the dose escalation scheme.

Approximately 3 - 4 months after completion of chemoradiation, radiologic response assessment will be performed. This will include cross-sectional imaging of the primary tumor (with CT scan and/or MRI) as well as a whole body FDG-PET (fluorodeoxyglucose positron emission tomography) scan.

All patients will receive standard treatment with definitive radiation therapy (IMRT, intensity modulated radiation therapy), administered as one fraction per day (Monday through Friday) over approximately 33 fractions. Patients with resected tumors will be treated to a maximum dose of 66 Gy. Patients with unresected tumors will be treated to a maximum dose of 70 Gy.

Patients will receive daily RAD0001 it will be administered orally or via percutaneous gastrostomy tube (PEG) once daily according to the dose escalation scheme plus cisplatin intravenously once per week (Days 1, 8, 15, 22, 29, 36) according to the dose escalation scheme.

Approximately 3 - 4 months after completion of chemoradiation, radiologic response assessment will be performed. This will include cross-sectional imaging of the primary tumor (with CT scan and/or MRI) as well as a whole body FDG-PET (fluorodeoxyglucose positron emission tomography) scan.

研究衡量的是什么?

主要结果指标

结果测量
大体时间
To establish the phase II recommended dose of oral RAD001 (everolimus) tablets + weekly intravenous cisplatin given concurrently with radiation therapy.
大体时间:3 months
3 months

次要结果测量

结果测量
大体时间
To evaluate the safety and tolerability of oral RAD001 + radiation therapy + intravenous cisplatin.
大体时间:3 months
3 months
To estimate the incidence of over-expression of eIF4E in surgical margins by immunohistochemistry (IHC).(only for those subjects who undergo primary surgery)
大体时间:3 months
3 months
To describe the pharmacokinetics of RAD001 administered by PEG (percutaneous gastrostomy) tube.
大体时间:3 months
3 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。

调查人员

  • 首席研究员:Matthew Fury, MD,PhD、Memorial Sloan Kettering Cancer Center

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

2009年3月1日

初级完成 (实际的)

2013年7月1日

研究完成 (实际的)

2013年7月1日

研究注册日期

首次提交

2009年3月6日

首先提交符合 QC 标准的

2009年3月6日

首次发布 (估计)

2009年3月10日

研究记录更新

最后更新发布 (估计)

2013年7月25日

上次提交的符合 QC 标准的更新

2013年7月23日

最后验证

2013年7月1日

更多信息

与本研究相关的术语

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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