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Contraceptive Agents, Hormonal

Prostate bed radiotherapy (PBRT) begins within 6 weeks (+/- 2 weeks) after registration.

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).

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).

1.8 Gy per fraction once daily, 5 days a week totaling 64.8-70.2 Gy. 3D-CRT or IMRT required.

PBRT

1.8 Gy per fraction once daily, 5 days a week, totaling 45 Gy. 3D-CRT or IMRT required.

PLNRT

Antiandrogen (AA) therapy can be either 250 mg flutamide by mouth three times a day or 50 mg bicalutamide by mouth once a day.

Luteinizing hormone-releasing hormone (LHRH) agonist can be any analog approved by the FDA (or by Health Canada for Canadian institutions) and may be given in any possible combination such that the total LHRH treatment time is 4-6 months. LHRH analogs are administered with a variety of techniques, including subcutaneous insertion of a solid plug in the abdominal wall, intramuscular injection, and subcutaneous injection.

LHRH agonist

Alan Pollack, MD, PhD

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.

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.

Tertiary

* To assess whether an incremental gain in FFP and survival with more aggressive therapy outweighs decrements in the primary generic domains of HRQOL (i.e., mobility, self care, usual activities, pain/discomfort, and anxiety/depression).
* To evaluate the cost-utility of the treatment arm demonstrating the most significant benefit (in terms of the primary outcome) in comparison with other widely accepted cancer and non-cancer therapies.
* To assess associations between serum levels of beta-amyloid and measures of cognition and mood and depression.
* An exploratory aim is to assess the relationship(s) between the American Urological Association Symptom Index (AUA SI) and urinary morbidity using the CTCAE v. 3.0 grading system.

OUTLINE: Patients are stratified according to seminal vesicle involvement (yes vs no), prostatectomy Gleason score (≤ 7 vs 8-9), pre-radiotherapy PSA (≥ 0.1 and ≤ 1.0 ng/mL vs \> 1.0 and \< 2.0 ng/mL), and pathology stage (pT2 and margin negative vs all others). Patients are randomized to 1 of 3 treatment arms.

Follow-up occurs 3, 6, and 12 months after the completion of radiation therapy, then every 6 months for 6 years, and then annually thereafter.

Prostate Radiation Therapy or Short-Term Androgen Deprivation Therapy and Pelvic Lymph Node Radiation Therapy With or Without Prostate Radiation Therapy in Treating Patients With a Rising Prostate Specific Antigen (PSA) After Surgery for Prostate Cancer

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

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.

Secondary biochemical (failure) is defined as either of two occurrences: 1. For detectable post-baseline PSA values (≥ 0.1), the first occurrence of a PSA value that is both ≥ 0.4 and a second rise above nadir; 2.The start of second salvage therapy. Failure time is defined as time from randomization to the date of failure, death (competing risk), or last known follow-up (censored). Failure rates for data summary are estimated using the cumulative incidence method, with 5-year rates provided here. Pairwise comparisons of the distributions of failure times, reported in the statistical analysis section, use cause-specific hazard rates for which deaths are censored. 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.

Hormone-refractory disease (failure) is defined as three rises in PSA after the start of second salvage androgen deprivation therapy. Failure time is defined as time from randomization to the date of failure, death (competing risk), or last known follow-up (censored). Failure rates for data summary are estimated using the cumulative incidence method, with 5-year rates provided here. Pairwise comparisons of the distributions of failure times, reported in the statistical analysis section, use cause-specific hazard rates for which deaths are censored. The study was designed for the final analysis to occur after all participants had been on study for at least 5 years, but the data monitoring committee decided to release results after the third interim analysis.

Local failure is defined as first occurrence of local clinical progression. Failure time is defined as time from randomization to the date of failure, death (competing risk), or last known follow-up (censored). Failure rates for data summary are estimated using the cumulative incidence method, with 5-year rates provided here. Pairwise comparisons of the distributions of failure times, reported in the statistical analysis section, use cause-specific hazard rates for which deaths are censored. The study was designed for the final analysis to occur after all participants had been on study for at least 5 years, but the data monitoring committee decided to release results after the third interim analysis.

Distant metastasis (failure) is defined as the occurrence of distant metastasis determined by imaging. Failure time is defined as time from randomization to the date of failure, death (competing risk), or last known follow-up (censored). Failure rates for data summary are estimated using the cumulative incidence method, with 5-year rates provided here. Pairwise comparisons of the distributions of failure times, reported in the statistical analysis section, use cause-specific hazard rates for which deaths are censored. The study was designed for the final analysis to occur after all participants had been on study for at least 5 years, but the data monitoring committee decided to release results after the third interim analysis.

Cause-specific mortality (failure) is defined as death due to prostate cancer or complications of protocol treatment (centrally reviewed), or death following disease progression (clinical or biochemical) in the absence of or after the initiation of any salvage therapy. \[Biochemical progression is indicated by any rise in PSA.\] Failure time is defined as time from randomization to the date of failure, death (competing risk), or last known follow-up (censored). Failure rates for data summary are estimated using the cumulative incidence method, with 5-year rates provided here. Pairwise comparisons of the distributions of failure times, reported in the statistical analysis section, use cause-specific hazard rates for which deaths are censored. The study was designed for the final analysis to occur after all participants had been on study for at least 5 years, but the data monitoring committee decided to release results after the third interim analysis.

Survival time is defined as time from randomization to the date of death from any cause or last known follow-up (censored). Survival rates are estimated by the Kaplan-Meier method. Pairwise comparisons of the overall distributions of failure times are reported in statistical analysis section, with five-year rates reported here. The study was designed for the final analysis to occur after all participants had been on study for at least 5 years, but the data monitoring committee decided to release results after the third interim analysis.

Common Terminology Criteria for Adverse Events (version 3.0) grades adverse event severity from 1=mild to 5=death. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data. Pairwise comparisons of Arm 2 vs Arm 1 and Arm 3 vs. Arm 2 are reported in the statistical analysis.

Common Terminology Criteria for Adverse Events (version 3.0) grades adverse event severity from 1=mild to 5=death. Late adverse events (AE) are defined as occurring \> 90 days from the completion of RT. Failure time is defined as time from randomization to the date of first late grade 2 or grade 3 adverse event, death (competing risk), or last known follow-up (censored). Failure rates for data summary are estimated using the cumulative incidence method, with 5-year rates provided here. Pairwise comparisons of the distributions of failure times between Arm 2 and Arm 1 and between Arm 3 and Arm 2, reported in the statistical analysis section, use cause-specific hazard rates for which deaths are censored.

National Cancer Institute (NCI)

Cancer and Leukemia Group B

NRG Oncology

Radiation Therapy Oncology Group

Eligible participants who started study treatment and have adverse event data.

PBRT Alone

Prostate bed radiotherapy (PBRT) and short term androgen deprivation therapy (STADT) consisting of antiandrogen (AA) and luteinizing hormone-releasing hormone (LHRH) agonist therapy begins within 6 weeks (+/- 2 weeks) after registration. STADT 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).

PBRT + STADT

Pelvic lymph node radiotherapy (PLNRT), prostate bed radiotherapy (PBRT), and short term androgen deprivation therapy (STADT) consisting of antiandrogen (AA) and luteinizing hormone-releasing hormone (LHRH) agonist therapy begins within 6 weeks (+/- 2 weeks) after registration. STADT 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).

PLNRT + PBRT + STADT

PBRT + STAD

PLNRT + PBRT + STAD

Total

Age, Continuous

Age (years)

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

0 = Asymptomatic; 1 = Symptomatic but completely ambulatory; 2 = Symptomatic, \<50% in bed during the day; 3 = Symptomatic, \>50% in bed, but not bedbound; 4 = Bedbound; 5 = Death

Zubrod Performance Status

Pathologic Seminal Vesicle Involvement

pT3 Extraprostatic extension NOS

pT3a Extraprostatic extension

pT3b Seminal vesicle invasion

Tumor stage per the American Joint Committee on Cancer (AJCC) 6th ed. 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.

Prostatectomy Tumor Stage

7: 3+4

7:4+3

7: primary/secondary not indicated

Gleason score describes prostate cancer based on how abnormal the cancer cells in a biopsy sample look under a microscope. Cells are scored 1-5 with 1 indicating "low-grade" looking similar to normal cells and 5 indicating "high-grade" barely resembling normal cells due to mutation. A pathologist assigns a Gleason grade to the first and second most predominant patterns in the biopsy. The two grades are added together to calculate the Gleason score (between 2 and 10). Cancers with lower scores tend to be less aggressive, while cancers with higher scores end to be more aggressive.

Gleason Score

Positive

Negative

Unknown

Prostatectomy Margins

Pelvic Lymphadenectomy

Number of Lymph Nodes Examined

Prostate-specific antigen (PSA) is a protein made by the prostate gland and found in the blood. PSA blood levels may be higher than normal in men who have prostate cancer, benign prostatic hyperplasia (BPH), or infection or inflammation of the prostate gland, and are often used to monitor patients who have been treated for prostate cancer to see if their cancer has recurred.

Pre-RT Entry PSA

>= 0.1 and <= 0.2 ng/ml

> 0.2 and <= 0.5 ng/ml

> 0.5 and <= 1.0 ng/ml

> 1.0 and < 2.0 ng/ml

Three interim analyses were planned when there were 397, 794, and 1191 eligible patients with five years of potential follow-up from the randomization date. Due to findings from the third interim analysis, the data monitoring committee recommended that study results be reported early for all arms, while recognizing that the originally planned full analysis will provide additional insight for the Arm 3 vs. Arm 2 comparison.

Wendy Seiferheld

Alternative hypotheses: 10% improvement in 5-year FFP in Arm 2 and 20% improvement in Arm 3, both relative to Arm 1, which has an assumed 5-year FFP of 70%. Sample size of 1587 (529/arm) with overall one-sided 0.025 alpha provides 90% power. Interim analyses (reported here) tested at one-sided significance level of 0.001. P\<0.001 indicates comparison crossed interim efficacy boundary. See Limitations and Caveats section.

(Arm 1) Prostate bed radiotherapy (PBRT) begins within 6 weeks (+/- 2 weeks) after registration.

(Arm 2) 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).

(Arm 3) 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).

Percentage of Participants Free From Progression (FFP) at 5 Years

Percentage of Participants With Secondary Biochemical Failure (Alternative Biochemical Failure)

Percentage of Participants Free From Hormone-refractory Disease (Castrate-resistant Disease)

Percentage of Participants With Local Failure

Percentage of Participants With Distant Metastasis

Percentage of Participants Who Died Due to Prostate Cancer (Cause-specific Mortality)

Percentage of Participants Alive (Overall Mortality)

Grade 2+

Grade 3+

Percentage of Participants Experiencing Grade 2+ and 3+ Adverse Events ≤ 90 Days of the Completion of Radiotherapy (RT)

Percentage of Participants Experiencing Late Grade 2+ and 3+ Adverse Events > 90 Days From the Completion of Radiotherapy (RT)

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)

Assessment of Mood and Depression Change Using QOL Measured by the Hopkins Symptom Checklist (HSCL-25)

Assessment and Comparison of Quality Adjusted Life Year (QALY) and Quality Adjusted FFP Year (QAFFPY)

Evaluation and Comparison of the Cost-utility Using EuroQoL - 5 Dimensions (EQ-5D)

Prognostic Value of Genomic and Proteomic Markers for the Primary and Secondary Clinical Endpoints

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Prostate Radiation Therapy or Short-Term Androgen Deprivation Therapy and Pelvic Lymph Node Radiation Therapy With or Without Prostate Radiation Therapy in Treating Patients With a Rising Prostate Specific Antigen (PSA) After Surgery for Prostate Cancer	NCT00567580	Prostate Cancer	PBRT PLNRT AA LHRH agonist	18 Years -	Radiation Therapy Oncology Group
Prostate Radiation Therapy or Short-Term Androgen Deprivation Therapy and Pelvic Lymph Node Radiation Therapy With or Without Prostate Radiation Therapy in Treating Patients With a Rising Prostate Specific Antigen (PSA) After Surgery for Prostate Cancer	NCT00567580	Prostate Cancer	PBRT PLNRT AA LHRH agonist	18 Years -	Radiation Therapy Oncology Group

Spots Global Cancer Trial Database for plnrt

Every month we try and update this database with for plnrt cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for plnrt

Every month we try and update this database with for plnrt cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for plnrt cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.