Everolimus Dose Finding Study for Stage IV or Recurrent Cervical Cancer
2014年2月13日 更新者:Accelerated Community Oncology Research Network
Phase I Everolimus Dose Finding Study for the Treatment of Stage IV or Recurrent, Non-resectable, Cervical Cancer With Standard Whole Pelvic Radiation Therapy in Combination With Weekly Cisplatin and Daily Everolimus
This Phase 1, single-site, dose-escalation study is being conducted to determine the maximum tolerated dose (MTD) of RAD001 as part of a specified combination regimen.
研究概览
详细说明
This Phase 1, single-site, dose-escalation study is being conducted to determine the MTD of RAD001 as part of a specified combination regimen.
The combination regimen will be standard field whole pelvic RT in combination with cisplatin at 40mg/m2 weekly with RAD001 at dose escalation daily starting at 5 mg qod, then 5 mg qd, then 10 mg qd during the period of whole pelvic radiation therapy.
研究类型
介入性
阶段
- 阶段1
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
女性
描述
Inclusion Criteria:
- Patients must have at least one measurable site of disease according to Response Evaluation Criteria in Solid Tumors criteria that has not been previously irradiated.
- Female patient aged ≥18 years.
- Patient has life expectancy of at least 12 weeks at study start.
- Patient has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at study start.
- Patient has diagnosis of stage IV or recurrent, non-resectable, cervical cancer at study start.
- Patient has received no prior chemotherapy.
Patient has adequate hematologic function:
- Absolute neutrophil count [ANC] ≥1500/μL
- Platelets ≥100,000/μL
- Hemoglobin > 9g/dL
Patient has adequate renal function:
- Serum creatinine ≤ 2.0 mg/dL
- Calculated creatinine clearance ≥ 50 mL/min
Patient has adequate hepatic function:
- Serum bilirubin ≤1.5 x ULN
- ALT and AST ≤2.5 × ULN (≤ 5 x ULN in patients with liver metastases)
- INR <1.5 (or < 3 on anticoagulants)
- Patient has fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L AND fasting triglycerides ≤ 2.5 x ULN.
- Patient is able to provide signed informed consent.
Exclusion Criteria:
- Patient has neuroendocrine or small cell carcinoma of the cervix.
- Patient has previously used any biologic therapy with VEGF, VEGFR, or ErbB1/ErbB2 inhibitors.
- Patient is currently receiving anticancer therapies or has received anticancer therapies within 4 weeks of the start of study drug (including chemotherapy, radiation therapy, antibody based therapy, etc.).
- Patient has had a major surgery or significant traumatic injury within 4 weeks of start of study drug; patient has not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or patient might require major surgery during the course of the study.
- Patient has had prior treatment with any investigational drug within the preceding 4 weeks before study start.
- Patient is receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent. Topical or inhaled corticosteroids are allowed.
- Patients should not receive immunization with attenuated live vaccines within one week of study entry or during study period. Patients should also avoid close contact with people who have received live vaccines during treatment with everolimus. Examples of live vaccines are: intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, and TY21a typhoid vaccines.
- Patient has known brain or leptomeningeal metastases.
- Patient has had other malignancies within the past 3 years except for adequately treated squamous cell carcinomas of the skin.
Patients has any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
- Symptomatic congestive heart failure of New York Heart Association Class III or IV.
- Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease.
- Severely impaired lung function defined as spirometry and diffusing capacity (DLCO) that is 50% of the normal predicted value and/or O2 saturation that is 88% or less at rest on room air.
- Uncontrolled diabetes as defined by fasting serum glucose >1.5 × ULN.
- Active (acute or chronic) or uncontrolled severe infections.
- Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis.
- Patient has a known history of human immunodeficiency virus seropositivity.
- Patient has 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).
- Patient has an active, bleeding diathesis.
- Female patient who is pregnant or breast feeding, or an adult of reproductive potential who is not using effective birth control methods. If barrier contraceptives are being used, these must be continued throughout the trial and for up to 8 weeks after ending treatment by both sexes. Hormonal contraceptives are not acceptable as a sole method of contraception. (Women of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to administration of RAD001.)
- Patient has received prior treatment with an mTOR inhibitor (sirolimus, temsirolimus, everolimus).
- Patient has a known hypersensitivity to RAD001 (everolimus) or other rapamycins (sirolimus, temsirolimus) or to its excipients.
- Patient has history of noncompliance to medical regimens.
- Patient is unwilling to or unable to comply with the protocol.
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:Single arm
All subjects receive RAD001 in combination with standard field whole pelvic radiation and cisplatin.
|
RAD001 will be administered orally as 5 mg qod, 5 mg qd, or 10mg qd continuously from study Day 1 until the end of whole pelvic radiation therapy unless the patient develops progression of disease or unacceptable toxicity prior to that.
其他名称:
Cisplatin will be administered intravenously once weekly at 40mg/m2 for 6 weeks.
The preferred administration day is Monday.
其他名称:
Patients will receive 180 cGy daily fraction Monday through Friday x 25 days (4500 cGy total) using a four field technique throughout the entire treatment with all fields treated each day.
|
研究衡量的是什么?
主要结果指标
结果测量 |
大体时间 |
---|---|
To determine the maximum tolerated dose for RAD001 as adjunct therapy to standard upfront treatment of advanced stage cervical cancer in combination with weekly cisplatin and whole pelvic external beam radiation
大体时间:every 7 days
|
every 7 days
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To determine the dose limiting toxicities for RAD001 as adjunct therapy to standard upfront treatment of advanced stage cervical cancer in combination with weekly cisplatin and whole pelvic external beam radiation
大体时间:every 7 days
|
every 7 days
|
次要结果测量
结果测量 |
大体时间 |
---|---|
To determine the pharmacokinetics of RAD001 given as adjunct therapy to standard upfront treatment of advanced stage cervical cancer
大体时间:day 1 and day 15 during study treatment
|
day 1 and day 15 during study treatment
|
To evaluate the pharmacogenetics of RAD001 in the specified patient population
大体时间:day 1 prior to starting study treatment
|
day 1 prior to starting study treatment
|
To evaluate microvessel density pre-and post-treatment with the specified treatment regimen in the specified patient population
大体时间:day 1 and end of treatment
|
day 1 and end of treatment
|
To evaluate potential correlations between biomarkers HIF-1a, TSP-1, P53, VEGF, and VEGFR and use of the specified treatment regimen in the specified patient population
大体时间:day 1 and end of treatment
|
day 1 and end of treatment
|
To evaluate progression free survival in the specified patient population
大体时间:from the time of treatment start until progression or up to 5 years after completion of study treatment
|
from the time of treatment start until progression or up to 5 years after completion of study treatment
|
To assess quality of life as indicated by the Patient Care Monitor in the specified patient population
大体时间:every 7 days during study treatment
|
every 7 days during study treatment
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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。
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12月1日
初级完成 (预期的)
2010年12月1日
研究完成 (预期的)
2010年12月1日
研究注册日期
首次提交
2009年8月27日
首先提交符合 QC 标准的
2009年8月27日
首次发布 (估计)
2009年8月28日
研究记录更新
最后更新发布 (估计)
2014年2月14日
上次提交的符合 QC 标准的更新
2014年2月13日
最后验证
2014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.
RAD001的临床试验
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Children's Hospital Medical Center, CincinnatiNovartis完全的
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University of Alabama at BirminghamNational Cancer Institute (NCI); Children's Hospital of Philadelphia; Washington University School... 和其他合作者完全的
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Novartis Pharmaceuticals完全的
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Radiation Therapy Oncology GroupNational Cancer Institute (NCI); NRG Oncology完全的
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Guangdong Provincial People's HospitalNovartis未知
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