Phase I/II Study of Preoperative Radiation and Docetaxel Activity in High Risk Localized Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 25
- 试验地点
- 2
- 主要终点
- Maximum Tolerated Dose (MTD)
研究概览
简要总结
RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving radiation therapy together with chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
PURPOSE: This phase I/II trial is studying the side effects and best dose of docetaxel when given together with radiation therapy and to see how well they work in treating patients who are undergoing surgery for high-risk localized prostate cancer.
详细描述
OBJECTIVES:
Primary
- Determine the maximum tolerated dose (MTD) of neoadjuvant radiotherapy and docetaxel in patients who are undergoing prostatectomy for high-risk localized prostate cancer.
- Determine the pathologic response rate in patients treated at the phase II dose.
Secondary
- Determine the prostate-specific antigen (PSA) short-term response rate in patients treated with this regimen.
- Determine the long-term safety of this regimen prior to radical prostatectomy in these patients.
- Determine the clinical response to this regimen by urologic examination of these patients.
- Determine the surgical margin status at the time of prostatectomy in patients treated with this regimen.
- Determine the effect of this regimen, in terms of Health-Related Quality of Life by Expanded Prostate Cancer Index Composite (EPIC) and urinary symptom scores by the American Urological Association's measures, in these patients.
- Determine the clinical progression-free rate in patients treated with this regimen.
- Identify pretreatment predictors of response in these patients by examining tissue biomarkers in preserved pretreatment biopsy specimens.
- Determine the biologic impact of this regimen on these patients by examining the prostatectomy specimens.
- Collect frozen serum for future analysis of correlative biomarkers.
- Compare the RNA content (gene expression profile) of pre- and post-treatment tumor specimens in order to describe the molecular impact of this regimen on prostate cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 100 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Phase I Dose 1-4
Group 1=radiation only; Group 2=Docetaxel IV over 30mins, 10mg/m2; weekly x 5 weeks starting on day one of radiation; Group 3=Docetaxel IV over 30mins, 20mg/m2; weekly x 5 weeks starting on day one of radiation; Group 4=Docetaxel IV over 30mins, 30mg/m2; weekly x 5 weeks starting on day one of radiation
Radiation: All men receive same radiation treatment protocol. External Beam, 45 Gy (1.8 Gy fractions), 5 per week (daily) x 5 weeks (25 fractions)
干预措施: Intensity-Modulated Radiation Therapy (IMRT) (Radiation)
Phase I Dose 1-4
Group 1=radiation only; Group 2=Docetaxel IV over 30mins, 10mg/m2; weekly x 5 weeks starting on day one of radiation; Group 3=Docetaxel IV over 30mins, 20mg/m2; weekly x 5 weeks starting on day one of radiation; Group 4=Docetaxel IV over 30mins, 30mg/m2; weekly x 5 weeks starting on day one of radiation
Radiation: All men receive same radiation treatment protocol. External Beam, 45 Gy (1.8 Gy fractions), 5 per week (daily) x 5 weeks (25 fractions)
干预措施: Docetaxel+IMRT (Drug)
Phase II MTD Dose
Phase II with no phase I dose-limiting toxicities=Docetaxel IV over 30mins, 30mg/m2; weekly x 5 weeks starting on day one of radiation
Radiation: All men receive same radiation treatment protocol. External Beam, 45 Gy (1.8 Gy fractions), 5 per week (daily) x 5 weeks (25 fractions)
干预措施: Docetaxel+IMRT (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD)
时间窗: 5 weeks
Maximal tolerated dose (MTD) of the combination radiation (45 Gy) and docetaxel. The dose of radiation will be fixed at 45 Gy while the dose of docetaxel will be escalated. The starting dose of docetaxel will be 10 mg/m2 and will be escalated in increments of 10 mg/m2 up to a dose of 30 mg/m2 the pre-planned ceiling). MTD will be the dose that is associated with no more than 1 dose limiting toxicity (DLT) up to 6 patients. The DLT will be defined as clinically significant grade 3 non-hematologic or grade 4 hematologic toxicity, attributable to the chemoirradiation. If 2 of 3 patients experience a DLT, dose escalation will stop and the previous dose level will be considered the MTD. If 1 of 3 has DLT, additional 3 patients will be enrolled at the same dose level. If none of the additional 3 patients has DLT, the dose escalation will continue. If 1 additional patient has DLT, the previous dose will be considered the MTD and dose escalation will be stopped.
Pathologic Response Rate at the Phase II Dose
时间窗: 4-6 weeks after study treatment
Pathologic response rate is determined post-prostatectomy by pathologist laboratory analyses. The TNM system is the most widely used cancer staging system. Most hospitals and medical centers use the TNM system as their main method for cancer reporting. In the TNM system: The T refers to the size and extent of the main/primary tumor. T1, T2, T3, T4: Refers to the size and/or extent of the main tumor. The higher the number after the T, the larger the tumor or the more it has grown into nearby tissues. T's may be further divided to provide more detail, such as T3a and T3b.
次要结局
- Clinical Response to Treatment as Measured by Urologic Examination(Each participant was examined 3, 6, 9, 12 months, and annually for an average of 10 years after surgery.)
- Surgical Margin Status at Time of Prostatectomy (Count of Subjects With Negative Surgical Margins)(5 weeks)
- Prostate-specific Antigen Short-term Response Rate Measured as a Percentage Change in PSA(Baseline (pre-treatment) and 1 month after surgery (post-treatment))
- Clinical Progression-free Rate as Determined by <0.1ng PSA Results(3, 6, 9, 12 months and annually, up to 5 years)
- Long-term Safety(Regular intervals both study-related and clinical standard of care-related; assessed at end of study treatment. Average timeframe to follow safety was 1 year and includes all grade 3-4 adverse events)
- Efficacy Assessed Using Health-Related Quality of Life by Expanded Prostate Cancer Index Composite and Urinary Symptom Scores by American Urological Association's Measures(Baseline and 12 Months Post-Prostatectomy)
研究者
Mark Garzotto, MD
Principal Investigator
OHSU Knight Cancer Institute