Symptoms and General Pathology

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Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

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Prostatic Neoplasms

Neoplasm Metastasis

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Antineoplastic Agents

All Drugs and Chemicals

Anti-Inflammatory Agents

Docetaxel

Prednisone

Sunitinib

Tubulin Modulators

Antimitotic Agents

Angiogenesis Inhibitors

Growth Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

4 cycles of 70 mg/m2 Docetaxel + 37.5 mg daily Sunitinib for 14 days followed by a 7 day break for 3 cycles + external beam radiotherapy to 66 Gray over 6-7 weeks

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.

EBXRT

Andrew J Armstrong, MD, ScM

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.

Multimodality Phase II Study in Prostate Cancer

Multimodality Therapy for Recurrent High Risk Prostate Cancer: A Phase II Study

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.

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.

Local recurrence is defined as men with locally recurrent disease confirmed pathologically within the radiation field, and is estimated at 2 and 3 years.

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.

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.

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.

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.

Pfizer

Sanofi

Duke University

The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov

Multimodality

Age, Continuous

Sex: Female, Male

Andrew J. Armstrong, MD ScM FACP

The Rate of Progression Free Survival (PFS) at 24 Months

24 Months

36 Months

Proportion of Biochemical Progression (bPFS Proportion) at 2 and 3 Years.

Rate of Local Recurrence at 2 and 3 Years

This rate is not estimable as 0 patients had locally recurrent disease before being taken off study for biochemical progression.

Metastasis-free Survival (MFS) Rates at 2 and 3 Years.

Urinary Irritative (N=20)

Urinary Incontinence (N=21)

Bowel (N=19)

Sexual (N=21)

Only participant who adequately completed the sub-section of each questionnaire are included in the analysis population. Some participants did not answer a sufficient number of questions to adequately score a domain and therefore were not included.

Change in Quality of Life (QoL) After 1 Year

Urinary Irritative (N=29)

Urinary Incontinence (N=31)

Bowel (N=32)

Sexual (N=30)

Change in Quality of Life (QoL) After 3 Month

Due to the unavailability of tissue, this outcome was not performed.

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.

Overall Study

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Sodium Acetate C11

Fabio Almeida, M.D.

Positron emission tomography (PET) imaging evaluation in men with recurrent prostate cancer to select patients who may benefit from directed therapy

The goal of this project is improved imaging of prostate cancer by positron emission tomography (PET) with use of the radiopharmaceutical C-11 Acetate, utilizing state-of-the-art PET/CT camera technology and processing algorithms.

A successful effort will lead to more accurate diagnosis of recurrence in patients with prostate cancer to allow for early directed therapy. This study is designed to generate data to add to the understanding of the effectiveness of C-11 Acetate, focusing on patients with recurrent or persistent disease after prostatectomy or radiation therapy.

The study is designed to expand on the database of C11-Acetate PET imaging in patients with prior definitive therapy for prostate cancer and evidence of biochemical recurrence (post therapy rise in PSA), and to evaluate the relationship between detection on C11-Acetate PET imaging, PSA (Trigger, Velocity and Doubling Time) and FDG PET imaging.

Specific questions to be addressed:

1. What is the yield of current state-of-the-art PET/CT with C-11 Acetate in detecting recurrent disease in this patient population?
2. How does the performance of PET with C-11 Acetate compare with that of PET using F-18 fluorodeoxyglucose (FDG-PET), Sodium F18 PET bone scans and with that of CT?
3. What is the optimal imaging protocol in terms of imaging time after injection?

PET Imaging Characteristics of C11-Acetate in Patients With Recurrent Prostate Carcinoma

Phase 2 Study: PET Imaging Characteristics of C11-Acetate in Patients With Prostate Carcinoma, Detection of Recurrent Disease With PSA Relapse

Imaging studies will be evaluated both qualitatively and quantitatively using SUV (standardized uptake values): a measure of metabolism based on injected dose, patient weight and region of interest.

PSA will be monitored per routine clinical follow-up.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Multimodality Phase II Study in Prostate Cancer	NCT00734851	Prostate Cancer	Docetaxel Sunitinib EBXRT	18 Years -	Duke University
PET Imaging Characteristics of C11-Acetate in Patients With Recurrent Prostate Carcinoma	NCT01304485	Prostate Cancer	Sodium Acetate ...	18 Years -	Phoenix Molecular Imaging
PET Imaging Characteristics of C11-Acetate in Patients With Recurrent Prostate Carcinoma	NCT01304485	Prostate Cancer	Sodium Acetate ...	18 Years -	Phoenix Molecular Imaging

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