This is a single arm phase II study of docetaxel, prednisone, and sunitinib systemic therapy followed by salvage external beam radiation therapy for men who have experienced PSA recurrence following initial radical prostatectomy for prostate cancer. The primary aim is the rate of progression-free survival at 2 years as measured by lack of PSA progression and no evidence of disease. We hypothesize that this aggressive initial systemic therapy will improve the long term remission rates for men who are undergoing salvage radiation therapy for PSA recurrence in the absence of metastatic disease.
In many common malignancies such as breast cancer, trimodality therapy represents the standard-of-care approach, including initial surgical resection followed by systemic chemotherapy followed by radiotherapy for optimal local control, and targeted hormonal or biologic therapy for a period of time to reduce the ongoing risk of systemic disease recurrence. These approaches have reduced recurrence rates and improved overall survival in the adjuvant setting in breast cancer; however, the treatment of men with PSA recurrence following radical prostatectomy has generally been unsatisfying, given the high rates of persistent or recurrent disease despite salvage radiotherapy. The primary purpose of the study is to determine the rate of biochemical (PSA) progression free survival (bPFS) in men with PSA recurrent non-metastatic prostate cancer following radical prostatectomy, who receive multimodality therapy consisting of local salvage external beam radiotherapy and systemic docetaxel-based chemotherapy plus the targeted anti-VEGF biologic therapy sunitinib. Biochemical PFS will be defined as the proportion of subjects at 24 months, post-registration, with one of the following: 1) a serum PSA value of 0.2 ng/ml or more above the post-radiotherapy PSA nadir and confirmed 4 weeks later by a second PSA measurement that was higher than the first by any amount, 2) a continued rise in the PSA level following study treatment if no nadir is experienced, defined as 2 rising values greater than the baseline PSA and separated by at least 4 weeks, 3) evidence of clinical progression or initiation of systemic therapy for progressive disease, or 4) death. Secondary objectives include finding the rate of biochemical (PSA) disease free survival over time, Two-, three-, five-, and six- year risk of local recurrence (proportion), two-, three-, five-, and six-year risk of metastases and metastasis-free survival, two-, three-, five-, and six-year risk of metastases and metastasis-free survival, Safety, feasibility, and tolerability as assessed by NCI Common Toxicity Scales (v3.0), quality of life questionnaire (EPIC-short form surveys), achievement of accrual goals. Finally, a comparison of RNA expression profiles from original prostate radical prostatectomy specimen among those with PSA relapse at 2 and 5 years as compared to those without PSA relapse at the primary endpoint.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
36
Docetaxel 70 mg/m2 day 1 every 3 weeks for 4 cycles with prednisone 5 mg orally twice daily
Sunitinib 37.5 mg orally once daily for 14 days followed by 7 days off, for 4 cycles, concurrent with docetaxel and prednisone
External beam radiotherapy to the prostate bed, started on day 100, after completion of chemotherapy. 66 Gy over 6-7 weeks.
Johns Hopkins University
Baltimore, Maryland, United States
The Cancer Institute of New Jersey
New Brunswick, New Jersey, United States
Duke University
Durham, North Carolina, United States
The Rate of Progression Free Survival (PFS) at 24 Months
Percentage of participants surviving 24 months from the start of study treatment without progression of disease. PFS was defined as the time from the date of study treatment initiation to the date of the first documented progression. Progression will be defined as having experienced any of the following: a serum prostate specific antigen (PSA) value of 0.2 ng/mL or more above the post-radiotherapy PSA nadir and confirmed 4 weeks later by a second PSA measurement that was higher than the first by any amount, a continued rise in the PSA level following study treatment if no nadir is experienced, defined as 2 rising values greater than the baseline PSA and separated by at least 4 weeks, or evidence of clinical progression or initiation of systemic therapy for progressive disease.
Time frame: 2 years
Proportion of Biochemical Progression (bPFS Proportion) at 2 and 3 Years.
Percentage of participants surviving 24 and 36 months from the start of study treatment without progression of disease. PFS was defined as the time from the date of study treatment initiation to the date of the first documented progression. Progression will be defined as having experienced any of the following: a serum prostate specific antigen (PSA) value of 0.2 ng/mL or more above the post-radiotherapy PSA nadir and confirmed 4 weeks later by a second PSA measurement that was higher than the first by any amount or a continued rise in the PSA level following study treatment if no nadir is experienced, defined as 2 rising values greater than the baseline PSA and separated by at least 4 weeks. Please note: bPFS is identical to PFS but includes only PSA-based endpoints or death.
Time frame: 24 months and 36 months
Rate of Local Recurrence at 2 and 3 Years
Local recurrence is defined as men with locally recurrent disease confirmed pathologically within the radiation field, and is estimated at 2 and 3 years.
Time frame: 24 months and 36 months
Metastasis-free Survival (MFS) Rates at 2 and 3 Years.
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MFS is defined as the length of time between the date of start of treatment and the date of evidence of systemic disease on bone scan or cross sectional imaging or death, whichever occurs first.
Time frame: 2 and 3 years
Change in Quality of Life (QoL) After 1 Year
A validated scale of prostate-cancer specific quality of life will be measured using the Expanded Prostate Cancer Index Composite (EPIC) short form survey. This survey is standardized into subscale, 4 of which were examined on this study. These subscales are the urinary irritative domain, urinary incontinence domain, bowel domain, and sexual function domain, each standardized on a scale of 0-100, where higher score indicate a higher level of QoL. The survey was performed at baseline, at 3 months after completing radiotherapy, at 12 months, and at 2 and 3 years of follow-up for a total of 5 possible surveys per patient. Due to a low number of completed surveys at the fourth and fifth time point, the difference between the 12 month time point and baseline is summarized. Negative values indicate a decrease in QoL, while positive numbers represent an increase.
Time frame: baseline and 1 year
Change in Quality of Life (QoL) After 3 Month
A validated scale of prostate-cancer specific quality of life will be measured using the Expanded Prostate Cancer Index Composite (EPIC) short form survey. This survey is standardized into subscale, 4 of which were examined on this study. These subscales are the urinary irritative domain, urinary incontinence domain, bowel domain, and sexual function domain, each standardized on a scale of 0-100, where higher score indicate a higher level of QoL. The survey was performed at baseline and 3 months after completing radiotherapy. Negative values indicate a decrease in QoL, while positive numbers represent an increase.
Time frame: baseline and 3 months
Comparison of RNA Expression Profile From Original Prostate Radical Prostatectomy Specimen Among Those With PSA Relapse at 2 and 3 Years as Compared to Those Without PSA Relapse at the Primary Endpoint.
Prospective collection of prostate tissue at the time of radical prostatectomy is routinely performed at Duke. These samples will be analyzed by laser capture microdissection (LCM) for genomic profiling by RNA expression analysis for all subjects with tissue available. The expression profiles of subjects who experience PSA recurrence after protocol therapy by the 24 month endpoint will be compared with the expression profiles of subjects without recurrence at this time point as an exploratory measure to predict aggressive prostate cancer and those subjects who are unlikely to benefit from this approach. Baseline prostate tumor biomarkers in the form of RNA expression profiles will be correlated with 2 year PFS in an exploratory analysis. The median bPFS of those with detectable biomarker expression is reported.
Time frame: 2 and 3 years