Intensity Modulated Radiation Therapy for Prostate Cancer
2019年7月17日 更新者：Kevin Camphausen, M.D.、National Cancer Institute (NCI)
A Pilot Study of Image Guided Prostate and Pelvic Nodal Irradiation With Intensity Modulated Radiation Therapy (IMRT) in Prostate Cancer
BACKGROUND:
-This study represents a progression from findings in four previous National Cancer Institute (NCI) Radiation Oncology Branch (ROB) protocols (02-C-0167A, 02-C-0207E, 03-C-0190B, 04-C-0171). In these previous works we have begun to develop techniques to obtain Magnetic Resonance (MR) biological images and co-register tissue in prostate cancer patients.
OBJECTIVES:
-The primary objective of the first portion of this study is to assess the feasibility of using Intensity-modulated radiation therapy (IMRT) to treat the at-risk lymph nodes in prostate cancer. Also, if feasible, we hope optimize this technique with experience.
ELIGIBILITY:
-This is a study of image guided, targeted radiation therapy in patients with high risk of nodal metastases from prostate cancer. Patients with prostate cancer who have more than 15% risk of lymph node (as defined by the Partin tables) metastasis will be eligible for this study.
DESIGN:
- On the first 10 patients, we will perform approximately 5 computed tomography (CT) simulations throughout the course of their therapy. On each simulation, the initial treatment plan will be re-run. The dose-volume data from target and normal tissues will then be re-analyzed. From this analysis we will be better able to determine the size of margins needed to account for organ motion and changes such as varying amounts of gas in the bowel and fluid in the bladder. To the best of our knowledge, no such analyses have been published.
- If the initial part of this trial is feasible, we will proceed to a phase I dose escalation trial of radiation to the at-risk lymph nodes. The primary statistical objective of the phase I portion of this study is to estimate the Maximum Tolerated Dose (MTD) of external beam radiation based on evaluating acute toxicity. The study will be conducted with a dose-escalation design with 3 patients in each dose cohort. If fewer than 2 of 3 patients experience an acute dose limiting toxicity (DLT) than patients will be accrued to the next dose cohort. If 2 or more of 3 patients experience a DLT then the MTD will be exceeded and the prior, lower dose cohort will be considered the MTD. Secondary objectives of this study are to relate patterns in gene and protein expression to response and toxicity and to evaluate the frequency of late term toxicity.
- Specific procedures and risks will be described in a separate consent to be obtained at the time of biopsy. Tissue samples will be processed for complementary deoxyribonucleic acid (cDNA) microarray testing and stored for future analysis in the Radiation Oncology Branch, NCI.
- Anatomic Magnetic Resonance Imaging (MRI) and magnetic resonance (MR) biological images of the prostate and pelvis will be obtained and tissue will be acquired with biopsy locations precisely translated (co-registered) to an MR image of reference. A fiducial marker (gold seed) will be left at the biopsy site as a fiducial marker to direct future radiation therapy to the prostate. If necessary, additional fiducial markers will be placed for prostate localization during treatment.
研究概览
详细说明
BACKGROUND:
-This study represents a progression from findings in four previous National Cancer Institute (NCI) Radiation Oncology Branch (ROB) protocols (02-C-0167A, 02-C-0207E, 03-C-0190B, 04-C-0171). In these previous works we have begun to develop techniques to obtain Magnetic Resonance (MR) biological images and co-register tissue in prostate cancer patients.
OBJECTIVES:
-The primary objective of the first portion of this study is to assess the feasibility of using Intensity-modulated radiation therapy (IMRT) to treat the at-risk lymph nodes in prostate cancer. Also, if feasible, we hope optimize this technique with experience.
ELIGIBILITY:
- This is a study of image guided, targeted radiation therapy in patients with high risk of nodal metastases from prostate cancer.
- Patients with prostate cancer who have more than 15% risk of lymph node (as defined by the Partin tables) metastasis will be eligible for this study.
DESIGN:
- On the first 10 patients, we will perform approximately 5 computed tomography (CT) simulations throughout the course of their therapy. On each simulation, the initial treatment plan will be re-run. The dose-volume data from target and normal tissues will then be re-analyzed. From this analysis we will be better able to determine the size of margins needed to account for organ motion and changes such as varying amounts of gas in the bowel and fluid in the bladder. To the best of our knowledge, no such analyses have been published.
- If the initial part of this trial is feasible, we will proceed to a phase I dose escalation trial of radiation to the at-risk lymph nodes. The primary statistical objective of the phase I portion of this study is to estimate the Maximum Tolerated Dose (MTD) of external beam radiation based on evaluating acute toxicity. The study will be conducted with a dose-escalation design with 3 patients in each dose cohort. If fewer than 2 of 3 patients experience an acute dose limiting toxicity (DLT) than patients will be accrued to the next dose cohort. If 2 or more of 3 patients experience a DLT then the MTD will be exceeded and the prior, lower dose cohort will be considered the MTD. Secondary objectives of this study are to relate patterns in gene and protein expression to response and toxicity and to evaluate the frequency of late term toxicity.
- Specific procedures and risks will be described in a separate consent to be obtained at the time of biopsy. Tissue samples will be processed for complementary deoxyribonucleic acid (cDNA) microarray testing and stored for future analysis in the Radiation Oncology Branch, NCI.
- Anatomic Magnetic Resonance Imaging (MRI) and magnetic resonance (MR) biological images of the prostate and pelvis will be obtained and tissue will be acquired with biopsy locations precisely translated (co-registered) to an MR image of reference. A fiducial marker (gold seed) will be left at the biopsy site as a fiducial marker to direct future radiation therapy to the prostate. If necessary, additional fiducial markers will be placed for prostate localization during treatment.
研究类型
介入性
注册 (实际的)
19
阶段
- 第一阶段早期
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
-
-
Maryland
-
Bethesda、Maryland、美国、20892
- National Institutes of Health Clinical Center, 9000 Rockville Pike
-
-
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 90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
- INCLUSION CRITERIA:
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
Pathology report confirming adenocarcinoma of the prostate
Risk of lymph node metastasis greater than or equal to15% as defined by the Partin tables or biopsy proven positive lymph nodes
Tumor visible on magnetic resonance imaging (MRI)
No prior surgery, radiation, or chemotherapy for prostate cancer, with the exception of hormone therapy which may be given neoadjuvantly for up to four (4) months.
Age greater than 18 years old and less than 90 years old.
EXCLUSION CRITERIA:
Cognitively impaired patients who cannot give informed consent.
Patients with metastatic disease beyond the pelvis
Contraindication to biopsy
- Bleeding disorder
- Prothrombin time (PT)/partial thromboplastin time (PTT) greater than or equal to 1.5 times the upper limit of normal
- Platelets less than or equal to 50K
- Artificial heart valve
Contraindication to MRI
- Patients weighing greater than136 kgs (weight limit for the scanner tables)
- Allergy to magnetic resonance (MR) contrast agent
- Patients with pacemakers, cerebral aneurysm clips, shrapnel injury or implantable electronic devices.
Pre-existing and active prostatitis or proctitis
Other medical conditions deemed by the principal investigator (PI) or associates to make the patient ineligible for protocol investigations, procedures, and high-dose external beam radiotherapy.
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：非随机化
- 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：Arm 1- 5040cGy to the lymph nodes
5040Gray (cGy) to the lymph nodes
|
Radiation will be given in dose escalations from 5040 Gray (cGy) to a maximum of 5900 cGy to lymph nodes.
|
|
实验性的：Arm 2 - 5400cGy to the lymph nodes
5400Gray (cGy) to the lymph nodes
|
Radiation will be given in dose escalations from 5040 Gray (cGy) to a maximum of 5900 cGy to lymph nodes.
|
|
实验性的：Arm 3 - 5900cGy to the lymph nodes
5900Gray (cGy) to the lymph nodes
|
Radiation will be given in dose escalations from 5040 Gray (cGy) to a maximum of 5900 cGy to lymph nodes.
|
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 |
|---|---|---|
|
Number of Participants With Any Grade 2 Toxicity Using Intensity Modulated Radiation Therapy (IMRT) to Treat the At-risk Lymph Nodes in Prostate Cancer ( up to First 10 Patients)
大体时间：At one week, one month, 2 months, 3 months, 6 months, 9 months, 1 year, 18 months, 2 years, 30 months, and 3 years after radiation therapy
|
Radiation side effects were assessed by the Radiation Oncology Group (RTOG) Acute/Late Toxicity Grading Gastrointestinal and Genitourinary criteria.
Acute Grade 0 - no symptoms, Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, Grade 4 is life threatening, and Grade 5 is death directly related to radiation side effects.
Late toxicity is defined as occurring after 90 days.
|
At one week, one month, 2 months, 3 months, 6 months, 9 months, 1 year, 18 months, 2 years, 30 months, and 3 years after radiation therapy
|
|
Maximum Tolerated Dose (MTD) of External Beam Radiation to Pelvic Lymph Nodes of Interest in Patients Receiving Radiation Therapy for Prostate Cancer (After the First 10 Patients) In Arm 1, Arm 2, and Arm 3
大体时间：Completion of Treatment, an average of 8.5 weeks
|
Maximum tolerated dose (MTD) is defined as the dose level immediately below the dose level at which 2 or more in a cohort of either 3 or 6 patients experiences a dose limiting toxicity (DLT) attributed to radiation therapy.
An acute DLT will be defined as Radiation Therapy Oncology Group (RTOG) grade 3 or greater, acute gastrointestinal or genitourinary toxicity within 3 months after the completion of radiation.
|
Completion of Treatment, an average of 8.5 weeks
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Number of Participants With Grade 2 Late Gastrointestinal or Genitourinary Toxicity Assessed by the Radiation Oncology Group (RTOG) Criteria
大体时间：At median follow-up, approximately 28 months following radiation
|
Long-term effects and toxicity following intensity modulated radiation therapy (IMRT) dose escalation to the pelvic nodes were measured by the Radiation Oncology Group (RTOG) Criteria.
Lower GI/Pelvis grade 2 toxicity Diarrhea requiring parasympatholytic drugs (e.g.
Lomotil)/mucous discharge not necessitating sanitary pads/rectal or abdominal pain requiring analgesics and Genitourinary grade 2 defined as Frequency of urination or nocturia that is less frequent than every hour.
Dysuria, urgency, bladder spasm requiring local anesthetic (e.g.
Pyridium).
|
At median follow-up, approximately 28 months following radiation
|
|
Number of Participants With a Dose Limiting Toxicity (DLT)
大体时间：Within 3 months after completion of radiation
|
An acute Dose Limiting Toxicity (DLT) will be defined as Radiation Therapy Oncology Group (RTOG) grade 3 or greater, acute gastrointestinal or genitourinary toxicity within 3 months after the completion of radiation.
|
Within 3 months after completion of radiation
|
|
Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)
大体时间：Date treatment consent signed to date off study, approximately 8 years and 3.5 months.
|
Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0).
A non-serious adverse event is any untoward medical occurrence.
A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
|
Date treatment consent signed to date off study, approximately 8 years and 3.5 months.
|
|
Number of Participants With Grade 3 or 4 Acute and/or Late Gastrointestinal or Genitourinary Toxicity Assessed by the Radiation Oncology Group (RTOG) Criteria
大体时间：At median follow-up, approximately 28 months following radiation
|
Long-term effects and toxicity following intensity modulated radiation therapy (IMRT) dose escalation to the pelvic nodes were measured by the Radiation Oncology Group (RTOG) Criteria.
Grade 3 toxicity Lower GI/Pelvis is Diarrhea requiring parenteral support/severe mucous or blood discharge necessitating sanitary pads/abdominal distention (flat plate radiograph demonstrates distended bowel loops), Grade 3 toxicity Genitourinary Frequency with urgency and nocturia hourly or more frequently/dysuria, pelvis pain or bladder spasm requiring regular, frequent narcotic/gross hematuria with/without clot passage.
|
At median follow-up, approximately 28 months following radiation
|
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。
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
- Pollack A, Zagars GK, Starkschall G, Antolak JA, Lee JJ, Huang E, von Eschenbach AC, Kuban DA, Rosen I. Prostate cancer radiation dose response: results of the M. D. Anderson phase III randomized trial. Int J Radiat Oncol Biol Phys. 2002 Aug 1;53(5):1097-105. doi: 10.1016/s0360-3016(02)02829-8.
- Roach M 3rd, DeSilvio M, Lawton C, Uhl V, Machtay M, Seider MJ, Rotman M, Jones C, Asbell SO, Valicenti RK, Han S, Thomas CR Jr, Shipley WS; Radiation Therapy Oncology Group 9413. Phase III trial comparing whole-pelvic versus prostate-only radiotherapy and neoadjuvant versus adjuvant combined androgen suppression: Radiation Therapy Oncology Group 9413. J Clin Oncol. 2003 May 15;21(10):1904-11. doi: 10.1200/JCO.2003.05.004.
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 (实际的)
2005年9月19日
初级完成 (实际的)
2014年5月27日
研究完成 (实际的)
2018年4月18日
研究注册日期
首次提交
2006年6月19日
首先提交符合 QC 标准的
2005年9月20日
首次发布 (估计)
2005年9月21日
研究记录更新
最后更新发布 (实际的)
2019年7月19日
上次提交的符合 QC 标准的更新
2019年7月17日
最后验证
2019年7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.