Phase 2/3 Study of Dose-escalated External Beam Radiation Therapy With or Without Chemotherapy for High Risk Adenocarcinoma of the Prostate
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 2
- 试验地点
- 3
- 主要终点
- Phase 2 - Assessment of Number of Freedom From Failure Events in the Chemotherapy Arm
研究概览
简要总结
The purpose of this study is to compare the effects on prostate cancer using radiation therapy with or without chemotherapy.
详细描述
The recommended treatment for a high risk prostate cancer consists of a combination of radiation therapy and androgen suppression for 2-3 years. Recent studies have shown a survival advantage for chemotherapy for prostate cancer. Chemotherapy has already been successfully integrated in the treatment of other cancer types and is our belief that chemotherapy will prove to be beneficial for patients with high risk prostate cancer. However, a clinical study is necessary to compare the results good or bad of chemotherapy with radiation therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed prostate adenocarcinoma (within 365 days of randomization.
- •High-risk for recurrence as determined by evidence of at least one of the following: Gleason score 8-10, PSA > 20, T state T
- •Histological evaluation of prostate biopsy with assignment of a Gleason score to the biopsy material: Gleason score must be in the range 2-
- •> 6 cores are strongly recommended.
- •Clinical stages T1a- T3 N0 M0 as staged by the treating investigator. (AJCC Criteria 7th Ed.-appendix III).
- •PSA values < = 50 ng/ml within 90 days prior to randomization. Must be completed prior to biopsy or at least 21 days after prostate biopsy.
- •Absolute Neutrophil Count (ANC) > = 1,800 cells/mm³ within 90 days prior to randomization.
- •Platelets > = 100,000 cells/mm³ within 90 days prior to randomization.
- •Hemoglobin > 10 g/dl within 90 days prior to randomization.
- •ALT, AST, and total bilirubin within 1.5 X institutional upper normal limits within 90 days prior to randomization.
- •ECOG status 0-1 (appendix II) documented within 90 days of randomization.
- •Patient must sign study specific informed consent prior to randomization. Note: consent for legally authorized representative is not permitted.
- •Completed all requirements listed in section 4.0 within the specified time frames.
- •Able to start treatment within 56 days of randomization.
- •At least 18 years old and less than or equal to 75 years of age.
- •Men of child-producing potential must be willing to consent to use effective contraception while on treatment and for at least 3 months afterwards.
- •Medical oncology consultation prior to randomization and medically approved for chemotherapy treatment per protocol.
排除标准
- •Evidence of distant metastasis.
- •Pelvic lymph nodes > 1.5 cm in greatest dimension unless the enlarged lymph node is biopsied and negative.
- •Prior prostate cancer surgery including but not limited to prostatectomy, hyperthermia and cryosurgery.
- •Prior pelvic radiation for their prostate cancer.
- •Prior androgen deprivation.
- •Severe, active co-morbidity, defined as follows:
- •Active rectal diverticulitis, Crohn's disease affecting the rectum or ulcerative colitis. (Non-active diverticulitis and Crohn's disease not affecting the rectum are allowed).
- •Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months.
- •Myocardial infarction within the last 6 months.
- •Acute bacterial or fungal infection requiring intravenous antibiotics at the time of randomization.
- •Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive.
- •Prior allergic reaction to the drugs involved in this protocol.
- •Existing peripheral neuropathy > = grade
- •Prior systemic chemotherapy for prostate cancer.
- •History of proximal urethral stricture requiring dilatation.
- •Major medical, addictive or psychiatric illness which in the investigator's opinion, will prevent the consent process, completion of the treatment and/or interfere with follow-up.
- •Evidence of any other cancer within the past 5 years and < 50% probability of a 5 year survival. (Prior or concurrent diagnosis of basal cell or non-invasive squamous cell cancer of the skin is allowed.)
研究组 & 干预措施
Radiation + 24mo luteinizing hormone-releasing hormone (LHRH)
Conformal RT 79.2 Gy(RBE) total dose + 24 months LHRH agonist (androgen suppression).
干预措施: Luteinizing hormone-releasing hormone (LHRH) (Drug)
Radiation + 24mo luteinizing hormone-releasing hormone (LHRH)
Conformal RT 79.2 Gy(RBE) total dose + 24 months LHRH agonist (androgen suppression).
干预措施: Conformal Radiation Therapy (RT) (Other)
Radiation + Chemo + 6mo luteinizing hormone-releasing hormone
Conformal RT 79.2 Gy(RBE) total dose + Chemotherapy: Docetaxel 20mg/m2 x every 7 days x 8 weeks followed by 6 months LHRH (androgen suppression).
干预措施: Luteinizing hormone-releasing hormone (LHRH) (Drug)
Radiation + Chemo + 6mo luteinizing hormone-releasing hormone
Conformal RT 79.2 Gy(RBE) total dose + Chemotherapy: Docetaxel 20mg/m2 x every 7 days x 8 weeks followed by 6 months LHRH (androgen suppression).
干预措施: Docetaxel (Drug)
Radiation + Chemo + 6mo luteinizing hormone-releasing hormone
Conformal RT 79.2 Gy(RBE) total dose + Chemotherapy: Docetaxel 20mg/m2 x every 7 days x 8 weeks followed by 6 months LHRH (androgen suppression).
干预措施: Conformal Radiation Therapy (RT) (Other)
结局指标
主要结局
Phase 2 - Assessment of Number of Freedom From Failure Events in the Chemotherapy Arm
时间窗: No failures were reported at the time of study termination (22 months). This outcome was originally written to assess failure at 2 years. However, that end point was not reached.
Measurement of Freedom from Failure i.e. the first occurence of clinical failure (local recurrence, regional recurrence, or distant metastasis), biochemical failure by the Phoenix definition (Prostate Specific Antigen \[PSA\] \> = 2 ng/ml over the nadir PSA discounting bounces per the investigators discretion), or the start of salvage therapy including androgen deprivation. This study was terminated prior to the time frame of 2 years being reached. Therefore, this outcome was assessed at time of study closure (22 months).
Phase 2 - Assessment of Number of Freedom From Failure Event Comparing Chemotherapy Arm to Standard Treatment Arm
时间窗: at 5 years
This endpoint will be examined if decision is made to not move forward with phase 3 study. This study was terminated prior to a decision being made about moving on to a phase 3 study. Therefore, this outcome was not assessed.
Phase 2 - Cumulative Number of Incidences of Grade 3 or Higher Adverse Events.
时间窗: 2 years
Assessment will be performed using CTCAE v4 criteria. This study was terminated prior to the time frame of 2 years being reached. Therefore, this outcome was assessed at time of study closure (22 months).
Phase 3 - Assessment of the Number of Freedom From Failure (FFF) Events Comparing the Chemotherapy Arm to the Standard Treatment Arm.
时间窗: at 5 years
The events for FFF will be the first occurence of clinical failure (local recurrence, regional recurrence, or distant metastasis), biochemical failure by the Phoenix definition (PSA \> = ng/ml over the nadir PSA discounting bounces per the investigators discretion), or the start of salvage androgen deprivation. This study was terminated prior to a decision being made about moving on to a phase 3 study. Therefore, this outcome was not assessed.
次要结局
- Assessment of Total Number of Salvage Androgen Deprivation Use With Comparison of Arms.(At study closure (22 months))
- Assessment of Total Number of Survival Events With Comparison of Group Arms(at study closure (22 months))
- Assessment of Total Number of Biochemical Failure Events(at study closure (22 months))
- Assessment of Number of Grade 2 or Higher Genitourinary (GU) and Gastrointestinal (GI) Adverse Events(at 6 months)
- Assessment of Impotence by Summation of Relative Scores for Sexual Function From the EPIC Quality of Life Instrument.(Up to 10 years)
- Assessment of Number of GI and GU Adverse Events(at 3 years)
- Assessment of Total Number of Local/Distant Failures(at time of study closure (22 months))
- Assessment of Quality of Life - Summation of Relative Scores From the EPIC Instrument.(Up to 10 years)