This randomized phase II/III trial studies docetaxel, antiandrogen therapy, and radiation therapy to see how well it works compared with antiandrogen therapy and radiation therapy alone in treating patients with prostate cancer that has been removed by surgery. Androgen can cause the growth of prostate cells. Antihormone therapy may lessen the amount of androgen made by the body. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving antiandrogen therapy and radiation therapy with or without docetaxel after surgery may kill any remaining tumor cells.
PRIMARY OBJECTIVE: I. To assess the benefit of docetaxel as measured by improvement in freedom from progression (phase II) and subsequently metastasis free survival (phase III) when given in combination with radiation and androgen deprivation in treatment of high risk prostate cancer post-radical prostatectomy. SECONDARY OBJECTIVES: I. To assess overall survival. II. To assess local time to progression. III. To assess undetectable prostate-specific antigen (PSA) with a non-castrate testosterone at 2.5 years post treatment. IV. To assess the utility of genomic profiling in making adjuvant therapy decisions post-prostatectomy. V. To assess toxicity of docetaxel in the post-operative setting when combined with radiation and androgen deprivation therapy. VI. To assess treatment response by genomically defined sub-groups of prostate cancer patients. EXPLORATORY OBJECTIVE: I. To optimize quality assurance methodologies and processes for radiotherapy and imaging, with machine learning strategies. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive androgen deprivation therapy comprising leuprolide acetate, goserelin acetate, degarelix, bicalutamide, flutamide, or nilutamide for 6 months. Beginning 8 weeks after the start of androgen deprivation therapy, patients receive external beam radiation therapy (EBRT) for 7.5 weeks. ARM II: Patients receive androgen deprivation therapy and EBRT as in Arm I. Within 4-6 weeks after completion of radiation therapy, patients receive docetaxel intravenously (IV) over 1 hour on day 1 of every 21 days for 6 cycles in the absence of disease progression or unexpected toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years, then every 6 months for 3 years, and then yearly.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
612
Given orally (PO)
Given IM
Given IV
Undergo external beam radiation therapy
Given PO
Given IM
Given IM
Correlative studies
Given intramuscularly (IM)
Given IM
Drug
Mobile Infirmary Medical Center
Mobile, Alabama, United States
Fairbanks Memorial Hospital
Fairbanks, Alaska, United States
Cancer Center at Saint Joseph's
Phoenix, Arizona, United States
University of Arizona Cancer Center-Orange Grove Campus
Tucson, Arizona, United States
Banner University Medical Center - Tucson
Tucson, Arizona, United States
Freedom from progression (FFP) (Phase II)
Will be determined with a one-sided stratified log-rank test when 89 FFP events have been observed. Both unadjusted and adjusted hazard ratios and the respective 95% confidence interval will be computed. Events for FFP will be the first occurrence of biochemical failure by prostate specific antigen (PSA) \>= 0.4 ng/ml over the nadir PSA confirmed by a second PSA higher than the first by any amount, recurrence (local, regional or distant), institution of secondary androgen deprivation therapy and death from any cause.
Time frame: From time of randomization to first event, assessed up to 43 months
Metastasis free survival (MFS) (Phase III)
Will be measured with a one-sided stratified log-rank test when 282 MFS events have been observed. Both unadjusted and adjusted hazard ratios and the respective 95% confidence interval will be computed.
Time frame: From time of randomization to first occurrence of distant metastasis or death from any cause, assessed up to 9.5 years
Overall survival
Will be analyzed using log-rank methodology and Cox proportional models. Tests for violations of proportionality will performed for the survival models. Fine and Gray's regression also will be used. Both unadjusted and adjusted hazard ratios and the respective 95% confidence interval will be computed.
Time frame: Time to death from any cause assessed up to 2.5 years
Time to local progression
Both unadjusted and adjusted hazard ratios and the respective 95% confidence interval will be computed.
Time frame: Baseline to local or regional recurrence ignoring biochemical failure and distant recurrence and censoring for death, assessed up to 2.5 years
Proportion of undetectable prostate specific antigen (PSA) with a non-castrate testosterone
Both unadjusted and adjusted hazard ratios and the respective 95% confidence interval will be computed.
Time frame: At 2.5 years
Incidence of acute adverse events scored according to the Cancer Therapy Evaluation Program active version of the Common Terminology Criteria for Adverse Events
Will be compared to late grade 3+ adverse events. Univariate logistic regression will be used to model the distribution of acute adverse events. Multiple logistic regression will be used to model the distribution of acute adverse events adjusted for covariates. Both unadjusted and adjusted odds ratios and the respective 95% confidence interval will be computed and tested using a one-sided Chi-Square test statistic with the significance level of 0.025. Both unadjusted and adjusted hazard ratios and the respective 95% confidence interval will be computed.
Time frame: Up to 30 days post radiation therapy
Genomic profiling in making adjuvant therapy decisions
Both unadjusted and adjusted hazard ratios and the respective 95% confidence interval will be computed.
Time frame: Up to 9 years
Late grade 3+ adverse events scored according to the Cancer Therapy Evaluation Program active version of the Common Terminology Criteria for Adverse Events
Will be compared to acute adverse events. A Fine and Gray's regression model will be used to compare the treatment differences of time to late adverse event with and without adjusting for other covariates. Both unadjusted and adjusted odds ratios and the respective 95% confidence interval will be computed and tested using a one-sided. Will be estimated using the cause-specific hazard rate approach and tested using a significance level of 0.025. Both unadjusted and adjusted hazard ratios and the respective 95% confidence interval will be computed. At least the treatment arm, age, and race (as appropriate) will be considered when it is adjusted in the analysis.
Time frame: From protocol treatment starts to the worst late grade 3+ adverse event, assessed up to 9 years
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University of Arizona Cancer Center-North Campus
Tucson, Arizona, United States
NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro
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