A Phase III Trial of Short Term Androgen Deprivation With Pelvic Lymph Node or Prostate Bed Only Radiotherapy (SPPORT) in Prostate Cancer Patients With a Rising PSA After Radical Prostatectomy
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 1,792
- 试验地点
- 460
- 主要终点
- Percentage of Participants Free From Progression (FFP) at 5 Years
研究概览
简要总结
RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as flutamide, bicalutamide, and luteinizing hormone-releasing hormone agonist, may lessen the amount of androgens made by the body. It is not yet known which regimen of radiation therapy with or without androgen-deprivation therapy is more effective for prostate cancer.
PURPOSE: This randomized phase III trial is studying prostate radiation therapy to see how well it works compared with short-term androgen deprivation therapy given together with pelvic lymph node radiation therapy with or without prostate radiation therapy in treating patients with a rising PSA after surgery for prostate cancer.
详细描述
OBJECTIVES:
Primary
- To determine whether the addition of short-term androgen deprivation (STAD) to prostate bed radiotherapy (PBRT) improves freedom from progression (FFP) (i.e., maintenance of a prostate-specific antigen [PSA] less than the nadir+2 ng/mL, absence of clinical failure, and absence of death from any cause) for 5 years, over that of PBRT alone in men treated with salvage radiotherapy after radical prostatectomy.
- To determine whether STAD, pelvic lymph node radiotherapy (PLNRT), and PBRT improves FFP over that of STAD+PBRT and PBRT alone in men treated with salvage radiotherapy after radical prostatectomy.
Secondary
- To compare secondary biochemical failure, the development of hormone-refractory disease , distant metastasis, cause-specific mortality, and overall mortality at five years.
- To compare acute and late morbidity based on Common Toxicity Criteria for Adverse Effects (CTCAE), v. 3.0.
- To measure the expression of cell kinetic, apoptotic pathway, and angiogenesis-related genes in archival diagnostic tissue to better define the risk of FFP, distant failure, cause-specific mortality, and overall mortality after salvage radiotherapy for prostate cancer, independently of conventional clinical parameters now used.
- To quantify blood product-based proteomic and genomic (single nucleotide polymorphisms) patterns and urine-based genomic patterns before and at different times after treatment to better define the risk of FFP, distant failure, cause-specific mortality, and overall mortality after salvage radiotherapy for prostate cancer, independently of conventional clinical parameters now used.
- To assess the degree, duration, and significant differences of disease-specific health-related quality of life (HRQOL) decrements among treatment arms.
- To assess whether mood is improved and depression is decreased with the more aggressive therapy if it improves FFP.
- To collect paraffin-embedded tissue blocks, serum, plasma, urine, and buffy coat cells for future translational research analyses.
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 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Adenocarcinoma of the prostate treated primarily with radical prostatectomy, pathologically proven to be lymph node negative by pelvic lymphadenectomy (N0) or lymph node status pathologically unknown (undissected pelvic lymph nodes [Nx]), i.e. lymph node dissection is not required;
- •Any type of radical prostatectomy will be permitted, including retropubic, perineal, laparoscopic or robotically assisted. There is no time limit for the date of radical prostatectomy.
- •A post-radical prostatectomy entry prostate-specific antigen (PSA) of ≥ 0.1 and < 2.0 ng/mL at least 6 weeks (45 days) after prostatectomy and within 30 days of registration;
- •One of the following pathologic classifications:
- •T3N0/Nx disease with or without a positive prostatectomy surgical margin; or
- •T2N0/Nx disease with or without a positive prostatectomy surgical margin;
- •Prostatectomy Gleason score of 9 or less;
- •Zubrod Performance Status of 0-1;
- •No distant metastases, based upon the following minimum diagnostic workup:
- •History/physical examination (including digital rectal exam) within 8 weeks (60 days) prior to registration;
- •A computerized tomography (CT) scan of the pelvis (with contrast if renal function is acceptable; a noncontrast CT is permitted if the patient is not a candidate for contrast) or magnetic resonance imaging (MRI) of the pelvis within 120 days prior to registration;
- •Bone scan within 120 days prior to registration; if the bone scan is suspicious, a plain x-ray and/or MRI must be obtained to rule out metastasis.
- •Adequate bone marrow function, within 90 days prior to registration, defined as follows:
- •Platelets ≥ 100,000 cells/mm^3 based upon compete blood count (CBC);
- •Hemoglobin ≥ 10.0 g/dl based upon CBC (Note: The use of transfusion or other intervention to achieve Hgb ≥ 10.0 g/dl is recommended).
- •Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2 x the upper limit of normal within 90 days prior to registration;
- •Serum total testosterone must be ≥ 40% of the lower limit of normal (LLN) of the assay used (testosterone ÷ LLN must be ≥ 0.40) within 90 days prior to registration (Note: Patients who have had a unilateral orchiectomy are eligible as long as this requirement is met);
- •Patients must sign a study-specific informed consent prior to study entry.
排除标准
- •A palpable prostatic fossa abnormality/mass suggestive of recurrence, unless shown by biopsy under ultrasound guidance not to contain cancer;
- •N1 patients are ineligible, as are those with pelvic lymph node enlargement ≥ 1.5 cm in greatest dimension by CT scan or MRI of the pelvis, unless the enlarged lymph node is sampled and is negative;
- •Androgen deprivation therapy started prior to prostatectomy for > 6 months (180 days) duration. Note: The use of finasteride or dutasteride (±tamsulosin) for longer periods prior to prostatectomy is acceptable;
- •Androgen deprivation therapy started after prostatectomy and prior to registration (Note: The use of finasteride or dutasteride (±tamsulosin) after prostatectomy is not acceptable - must be stopped within 3 months after prostatectomy. Androgen deprivation therapy must be stopped within 3 months after prostatectomy);
- •Neoadjuvant chemotherapy before or after prostatectomy;
- •Prior chemotherapy for any other disease site if given within 5 years prior to registration;
- •Prior cryosurgery or brachytherapy of the prostate; prostatectomy should be the primary treatment and not a salvage procedure;
- •Prior pelvic radiotherapy;
- •Prior invasive malignancy (except non-melanomatous skin cancer) or superficial bladder cancer unless disease free for a minimum of 5 years [for example, carcinoma in situ of the oral cavity is permissible];
- •Severe, active co-morbidity, defined as follows:
- •History of inflammatory bowel disease;
- •History of hepatitis B or C; Blood tests are not required to determine if the patient has had hepatitis B or C, unless the patient reports a history of hepatitis.
- •Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months;
- •Transmural myocardial infarction within the last 6 months;
- •Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration;
- •Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration;
- •Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; AST or ALT are required; note, however, that laboratory tests for coagulation parameters are not required for entry into this protocol.
- •Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; Note, however, that human immunodeficiency viruses (HIV) testing is not required for entry into this protocol. The need to exclude patients with acquired immunodeficiency syndrome (AIDS) from this protocol is necessary because the treatments involved in this protocol may result in increased toxicity and immunosuppression.
- •Prior allergic reaction to the study drug(s) involved in this protocol.
研究组 & 干预措施
PBRT Alone
Prostate bed radiotherapy (PBRT) begins within 6 weeks (+/- 2 weeks) after registration.
干预措施: PBRT (Radiation)
PBRT + STAD
Prostate bed radiotherapy (PBRT) and short term androgen deprivation therapy (STAD) consisting of antiandrogen (AA) and luteinizing hormone-releasing hormone (LHRH) agonist therapy begins within 6 weeks (+/- 2 weeks) after registration. STAD starts first, 2 months (+/- 2 weeks) before radiotherapy (RT), and lasts for 4-6 months. LHRH can last 4-6 months. AA starts at the same time as LHRH (or up to 2 weeks prior ), lasts approximately 4 months, and should end on the last day of RT (+/- 2 weeks).
干预措施: PBRT (Radiation)
PBRT + STAD
Prostate bed radiotherapy (PBRT) and short term androgen deprivation therapy (STAD) consisting of antiandrogen (AA) and luteinizing hormone-releasing hormone (LHRH) agonist therapy begins within 6 weeks (+/- 2 weeks) after registration. STAD starts first, 2 months (+/- 2 weeks) before radiotherapy (RT), and lasts for 4-6 months. LHRH can last 4-6 months. AA starts at the same time as LHRH (or up to 2 weeks prior ), lasts approximately 4 months, and should end on the last day of RT (+/- 2 weeks).
干预措施: AA (Drug)
PBRT + STAD
Prostate bed radiotherapy (PBRT) and short term androgen deprivation therapy (STAD) consisting of antiandrogen (AA) and luteinizing hormone-releasing hormone (LHRH) agonist therapy begins within 6 weeks (+/- 2 weeks) after registration. STAD starts first, 2 months (+/- 2 weeks) before radiotherapy (RT), and lasts for 4-6 months. LHRH can last 4-6 months. AA starts at the same time as LHRH (or up to 2 weeks prior ), lasts approximately 4 months, and should end on the last day of RT (+/- 2 weeks).
干预措施: LHRH agonist (Drug)
PLNRT + PBRT + STADT
Pelvic lymph node radiotherapy (PLNRT), prostate bed radiotherapy (PBRT), and short term androgen deprivation therapy (STAD) consisting of antiandrogen (AA) and luteinizing hormone-releasing hormone (LHRH) agonist therapy begins within 6 weeks (+/- 2 weeks) after registration. STAD starts first, 2 months (+/- 2 weeks) before RT, and lasts for 4-6 months. LHRH can last 4-6 months. AA starts at the same time as LHRH (or up to 2 weeks prior ), lasts approximately 4 months, and should end on the last day of RT (+/- 2 weeks).
干预措施: PBRT (Radiation)
PLNRT + PBRT + STADT
Pelvic lymph node radiotherapy (PLNRT), prostate bed radiotherapy (PBRT), and short term androgen deprivation therapy (STAD) consisting of antiandrogen (AA) and luteinizing hormone-releasing hormone (LHRH) agonist therapy begins within 6 weeks (+/- 2 weeks) after registration. STAD starts first, 2 months (+/- 2 weeks) before RT, and lasts for 4-6 months. LHRH can last 4-6 months. AA starts at the same time as LHRH (or up to 2 weeks prior ), lasts approximately 4 months, and should end on the last day of RT (+/- 2 weeks).
干预措施: PLNRT (Radiation)
PLNRT + PBRT + STADT
Pelvic lymph node radiotherapy (PLNRT), prostate bed radiotherapy (PBRT), and short term androgen deprivation therapy (STAD) consisting of antiandrogen (AA) and luteinizing hormone-releasing hormone (LHRH) agonist therapy begins within 6 weeks (+/- 2 weeks) after registration. STAD starts first, 2 months (+/- 2 weeks) before RT, and lasts for 4-6 months. LHRH can last 4-6 months. AA starts at the same time as LHRH (or up to 2 weeks prior ), lasts approximately 4 months, and should end on the last day of RT (+/- 2 weeks).
干预措施: AA (Drug)
PLNRT + PBRT + STADT
Pelvic lymph node radiotherapy (PLNRT), prostate bed radiotherapy (PBRT), and short term androgen deprivation therapy (STAD) consisting of antiandrogen (AA) and luteinizing hormone-releasing hormone (LHRH) agonist therapy begins within 6 weeks (+/- 2 weeks) after registration. STAD starts first, 2 months (+/- 2 weeks) before RT, and lasts for 4-6 months. LHRH can last 4-6 months. AA starts at the same time as LHRH (or up to 2 weeks prior ), lasts approximately 4 months, and should end on the last day of RT (+/- 2 weeks).
干预措施: LHRH agonist (Drug)
结局指标
主要结局
Percentage of Participants Free From Progression (FFP) at 5 Years
时间窗: From randomization to five years.
Progression is defined as the first occurrence of the following events: biochemical failure by the Phoenix definition (prostate-specific antigen \[PSA\] ≥ 2 ng/ml over the nadir PSA), clinical failure (local, regional or distant), or death from any cause. The initiation of second salvage therapy before progression was a protocol violation and resulted in censoring. Progression time is defined as time from randomization to the date of progression, second salvage therapy (censored), or last known follow-up (censored). Freedom from progression rates are estimated using the Kaplan-Meier method. The study was designed for the final analysis to occur after all participants had been on study for at least 5 years, but results were reported early. See Limitations and Caveats section.
次要结局
- Assessment and Comparison of Quality Adjusted Life Year (QALY) and Quality Adjusted FFP Year (QAFFPY)(From the 6th week of radiation therapy to 5 years post radiation therapy.)
- Evaluation and Comparison of the Cost-utility Using EuroQoL - 5 Dimensions (EQ-5D)(From the 6th week of radiation therapy to 5 years post radiation therapy.)
- Prognostic Value of Genomic and Proteomic Markers for the Primary and Secondary Clinical Endpoints(Date of randomization to timepoint of the respective primary or secondary endpoint.)
- Percentage of Participants With Secondary Biochemical Failure (Alternative Biochemical Failure)(From randomization to last follow-up. Maximum follow-up at time of analysis was 10.5 years.)
- Percentage of Participants Free From Hormone-refractory Disease (Castrate-resistant Disease)(From randomization to last follow-up. Maximum follow-up at time of analysis was 10.5 years.)
- Percentage of Participants With Local Failure(From randomization to last follow-up. Maximum follow-up at time of analysis was 10.5 years.)
- Percentage of Participants With Distant Metastasis(From randomization to last follow-up. Maximum follow-up at time of analysis was 10.5 years.)
- Percentage of Participants Who Died Due to Prostate Cancer (Cause-specific Mortality)(From randomization to last follow-up. Maximum follow-up at time of analysis was 10.5 years.)
- Percentage of Participants Alive (Overall Mortality)(From randomization to last follow-up. Maximum follow-up at time of analysis was 10.5 years.)
- Percentage of Participants Experiencing Grade 2+ and 3+ Adverse Events ≤ 90 Days of the Completion of Radiotherapy (RT)(From randomization to 90 days after completion of radiotherapy (approximately 7-8 weeks).)
- Comparison of Disease-specific Health Related Quality of Life (HRQOL) Change by the Expanded Prostate Cancer Index Composite (EPIC), Hopkins Verbal Learning Test Revised (HVLT-R), Trail Making Test A & B, and Controlled Oral Word Association Test (COWAT)(From the 6th week of radiation therapy to 5 years post radiation therapy.)
- Percentage of Participants Experiencing Late Grade 2+ and 3+ Adverse Events > 90 Days From the Completion of Radiotherapy (RT)(AE: from 91 days after completion of RT (approximately 7-8 weeks) to last follow-up. Vital status: from randomization to last follow-up. Maximum follow-up at time of analysis was 10.5 years.)
- Assessment of Mood and Depression Change Using QOL Measured by the Hopkins Symptom Checklist (HSCL-25)(From the 6th week of radiation therapy to 5 years post radiation therapy.)
- Assessment of the Relationship(s) Between the American Urological Association Symptom Index (AUA SI) and Urinary Morbidity (Adverse Event Terms: Urinary Frequency/Urgency) Using the CTCAE v. 3.0 Grading System(From the 6th week of radiation therapy to 5 years post radiation therapy.)