Phase I Trial of High Dose Rate Brachytherapy Combined With Stereotactic Body Radiation Therapy for Intermediate Risk Prostate Cancer Patients
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 42
- 试验地点
- 2
- 主要终点
- Dose limiting toxicities (DLT) graded according to the National Cancer Institute, Common Toxicity Criteria (NCI, CTC), v 4.0
研究概览
简要总结
The first technology is called high dose rate brachytherapy. Brachytherapy is sometimes called internal radiation therapy. High dose rate brachytherapy is a procedure that involves temporarily placing radioactive material inside the patient's body for about 10-20 minutes. Then, the remainder of the radiation treatment will be given over a 3 week period using stereotactic body radiation therapy (SBRT). SBRT is a novel treatment modality that involves the delivery of very high individual doses of radiation to tumors with high precision. This allows the doctor to deliver the same amount of radiation in a much shorter time. The purpose of this study is to determine the safety of brachytherapy when combined with hypofractionated SBRT.
详细描述
Prostate cancer is the most common non cutaneous malignancy diagnosed in the United States. Men with newly diagnosed disease are currently stratified based on their PSA, Gleason score, and DRE into one of three groups: low risk, intermediate risk, or high risk. Low risk is defined as either Gleason score 6 or below, PSA <10, and T1-T2a. Intermediate risk is defined as T2b-T2c or Gleason score 7 or PSA 10-20 ng/ml. High-risk disease is defined as PSA >20 or Gleason >7 or T2c or greater. The current standard non-surgical treatment for men with intermediate risk prostate cancer is radiation therapy.
Recently, there have been multiple phase III trials demonstrating the benefit of radiation dose escalation in the treatment of both low risk, intermediate risk, and high risk prostate cancer. These trials have all used external beam radiation therapy and have set a new standard dose for radiation treatment for men with prostate cancer that has been endorsed by the NCCN.
In addition to increasing the total dose delivered by EBRT, dose escalation can be achieved using brachytherapy. The radiation can be delivered either with low activity radioactive seed sources (termed low dose rate or LDR brachytherapy) or using a temporary implant with a higher activity source (high dose rate or HDR brachytherapy). HDR brachytherapy is a standard of care in the United States and Europe to deliver a radiation boost to the prostate when combined with external beam radiation. Three large studies including over 500 men received a combination of EBRT and HDR. All reported excellent outcome with PSA progression free survival between 70-90% for men with both intermediate and high-risk disease.
Further, the rate of late GI/GU toxicity was quite low as well with late grade 3 GU toxicity ranging from 2.1-6.7%, late grade 4 GU toxicity of 0-1%, late grade 3 GI toxicity of 0-1% and late grade 4 GI toxicity of 0-0.5%.
In addition, a phase III randomized trial compared EBRT alone or EBRT combined with an HDR boost. This trial demonstrated a significant improvement in actuarial biochemical relapse-free survival is seen in favor of the combined brachytherapy schedule. However, this trial was criticized that the EBRT alone arm had a lower biologic radiation dose than the combined arm. A retrospective study from Memorial Sloan Kettering Cancer Center compared patients who received EBRT alone to 86.4 Gy with those who underwent HDR brachytherapy combined with EBRT. Dose escalation by adding HDR brachytherapy provided improved PSA relapse-free survival in the treatment of prostate cancer compared with ultra-high-dose EBRT, independent of risk group on multivariate analysis, with the most significant benefit for intermediate-risk patients. Finally, a systemic review of the literature compared results from EBRT alone, EBRT combined with LDR, and EBRT combined with HDR. This study concluded that combination of external beam radiotherapy and HDR brachytherapy results in a superior biochemical control and overall survival.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Adenocarcinoma of the prostate with intermediate risk disease T2b-T2c or Gleason score 7 or prostate specific antigen (PSA) 10-20 ng/ml, without metastatic disease
- •To rule out metastatic disease, patients must have the following tests:
- •Bone scan within 60 days prior to registration
- •Computed tomography (CT) of abdomen/pelvis within 60 days prior to registration
- •Karnofsky performance status > 70
- •Age > 18
- •PSA blood test within 60 days prior to registration
- •Prostate biopsy within 180 days prior to registration
- •Within 60 days prior to registration, hematologic minimal values:
- •Absolute neutrophil count > 1,500/mm^3
- •Hemoglobin > 8.0 g/dl
- •Platelet count > 100,000/mm^3
- •Men of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter
- •No history of previous pelvic irradiation
排除标准
- •History of urological surgery or procedures predisposing to GU complications after radiation, i.e., anastomoses, stricture repair, etc. (will be determined by radiation oncologist)
- •History of prior pelvic irradiation
- •Documented distant metastatic disease
- •Prior radical prostatectomy or cryosurgery for prostate cancer
结局指标
主要结局
Dose limiting toxicities (DLT) graded according to the National Cancer Institute, Common Toxicity Criteria (NCI, CTC), v 4.0
时间窗: Up to 3 months
Data analysis of phase I studies is descriptive. All estimates of dose-specific rates (e.g., response and toxicity) will be presented with corresponding confidence intervals using the exact method.
次要结局
- Acute and late hematologic toxicity profile of HDR and SBRT combination(Up to 5 years)
- Late nonhematologic toxicity profile(Up to 5 years)
- Correlation of dosimetric parameters, including dose-volume factors for bladder and rectum, with acute toxicity(Up to 5 years)
- Patient-reported outcomes, assessed by EPIC and AUA symptom score(Up to 5 years)