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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2010-00604 | Registry Identifier | CTRP (Clinical Trial Reporting Program) |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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This phase II trial is studying sorafenib tosylate and gene expression in patients undergoing surgery for high-risk localized prostate cancer. Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Studying samples of blood and tumor tissues in the laboratory from patients with prostate cancer may help doctors learn more about changes that occur in DNA after treatment with sorafenib tosylate
PRIMARY OBJECTIVES:
I. To compare the gene expression changes (transcript profiles) between pre- and post-treatment tumor specimens in order to determine the molecular impact of multi-kinase inhibition on prostate cancer. While this analysis will initially be targeted to tumor cells, gene expression changes in the surrounding stromal tissue may also be analyzed.
SECONDARY OBJECTIVES:
I. To determine if specific downstream protein effectors (i.e. ERK, AKT, and S6- kinase) of Sorafenib kinase targets are affected by changes in protein phosphorylation by immunohistochemistry.
II. To provide evidence that Sorafenib has significant anti-tumor effect by comparison of pre- and post-treatment immunohistochemical markers of apoptosis (caspase-3), cell proliferation (Ki-67), and angiogenesis (microvessel density).
III. To determine the pathologic complete response rate, defined as absence of cancer in the prostatectomy specimen.
IV. To determine rates of positive surgical margins, extracapsular extension, seminal vesicle and lymph node involvement with tumor in comparison with Memorial Sloan Kettering pre-operative nomogram predictions.
V. To determine the percentage of patients with a >= 25% and >= 50% decline in PSA while receiving Sorafenib.
VI. To determine tissue Sorafenib levels in prostate tumors after treatment and correlate with molecular, clinical, and/or pathologic outcomes.
VII. To describe changes in overall histology after treatment with Sorafenib and correlate with molecular and clinical outcomes.
VIII. To determine if patients with baseline alterations in phospho-ERK, phospho-AKT, and phospho-S6-kinase expression correlate with treatment related molecular, clinical, and/or pathologic outcomes.
IX. To collect tissue samples for future analysis of correlative biomarkers of prognosis or treatment response.
X. To collect frozen plasma for future analysis of correlative biomarkers of treatment response (no genetic analysis will be performed on these specimens).
OUTLINE:
Patients receive sorafenib tosylate orally (PO) twice daily (BID) on days 1-14. Treatment repeats every 2 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Beginning 1 or 2 days after completion of sorafenib tosylate, patients undergo radical prostatectomy on approximately day 43.
After completion of study treatment, patients are followed up for 6-10 weeks.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment (enzyme inhibitor) 48hr stop | Experimental | Patients receive sorafenib tosylate PO BID on days 1-14. Treatment repeats every 2 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Beginning 2 days after completion of sorafenib tosylate, patients undergo radical prostatectomy on approximately day 43. |
|
| Treatment (enzyme inhibitor) 24hr stop | Experimental | tients receive sorafenib tosylate PO BID on days 1-14. Treatment repeats every 2 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Beginning 1 day after completion of sorafenib tosylate, patients undergo radical prostatectomy on approximately day 43. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| sorafenib tosylate | Drug | Given PO |
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| Measure | Description | Time Frame |
|---|---|---|
| Efficacy as Assessed by Number of Patients With Changes Across Transcript Profiles by Microarray Analysis in Prostate Cancer Specimens, Specifically Those With Complete Pathologic Response. | Determined by changes across transcript profiles, by microarray analysis, in pre- versus post-treatment prostate cancer specimens (minimum 50 day time frame between these). Proportion of patients with complete pathologic response. | Pre- versus post-treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Complete Pathologic Response | Proportion of Patients with at least 50% decline in PSA on Day 1 of Cycle 2, Day 1 of Cycle 3, and on day of radical prostatectomy. | Day 1 of cycles 2 and 3, and day of radical prostatectomy. Each cycle is 2 weeks. |
| Number of Participants With at Least 25% Reduction in PSA |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Evan Yu | Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | Seattle | Washington | 98109 | United States |
Five subjects were screened for this study, deemed eligible and enrolled.
Subjects were screened and enrolled at a single site in Seattle, Washington, United States.
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| ID | Title | Description |
|---|---|---|
| FG000 | 48 Hour Drug Stop Point | Sorafenib 400mg taken orally twice per day for 41 days prior to radical prostatectomy. Last dose of study drug is the morning dose 2 days prior to surgery. |
| FG001 | 24 Hour Drug Stop Point |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| microarray analysis | Genetic | Correlative studies |
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| immunohistochemistry staining method | Other | Correlative studies |
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| gene expression analysis | Genetic | Correlative studies |
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| needle biopsy | Procedure | Correlative studies |
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| therapeutic conventional surgery | Procedure | Undergo prostatectomy |
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| laboratory biomarker analysis | Other | Correlative studies |
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| western blotting | Genetic | Correlative studies |
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| RNA analysis | Genetic | Correlative studies |
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Proportion of Patients with at least 25% decline in PSA on Day 1 of Cycle 2, Day 1 of Cycle 3, and on day of radical prostatectomy. |
| Day 1 of cycles 2 and 3 and on the day of radical prostatectomy. Each cycle is 2 weeks. |
Sorafenib 400mg taken orally twice per day for 42 days prior to radical prostatectomy. Last dose of study drug is the morning dose the day prior to surgery.
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | 48 Hour Drug Stop Point | Sorafenib 400mg taken orally twice per day for 41 days prior to radical prostatectomy. Last dose of study drug is the morning dose 2 days prior to surgery. |
| BG001 | 24 Hour Drug Stop Point | Sorafenib 400mg taken orally twice per day for 42 days prior to radical prostatectomy. Last dose of study drug is the morning dose the day prior to surgery. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| Baseline PSA | Median | Full Range | ng/mL |
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| Gleason Score at Diagnosis | Gleason score is the sum of 2 numbers,each between 1-5, representing the pattern of tumor cells seen by a pathologist reviewing a prostate biopsy. 1 is given to cells that resemble normal cells. 5 is given to cells that least resemble normal cells. 1st number represents the most predominant cell pattern in a prostate biopsy, 2nd number represents the 2nd most predominant cell pattern in the same biopsy. Gleason score is the sum of these numbers. Lower Gleason scores (2-4) have been associated with less aggressive cancers, higher Gleason scores have been associated with more aggressive cancers. | Median | Full Range | units on a scale |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Efficacy as Assessed by Number of Patients With Changes Across Transcript Profiles by Microarray Analysis in Prostate Cancer Specimens, Specifically Those With Complete Pathologic Response. | Determined by changes across transcript profiles, by microarray analysis, in pre- versus post-treatment prostate cancer specimens (minimum 50 day time frame between these). Proportion of patients with complete pathologic response. | Data not collected | Posted | Pre- versus post-treatment |
|
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| Secondary | Number of Participants With Complete Pathologic Response | Proportion of Patients with at least 50% decline in PSA on Day 1 of Cycle 2, Day 1 of Cycle 3, and on day of radical prostatectomy. | One patient did not have lab samples collected on day of radical prostatectomy. | Posted | Count of Participants | Participants | Day 1 of cycles 2 and 3, and day of radical prostatectomy. Each cycle is 2 weeks. |
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| Secondary | Number of Participants With at Least 25% Reduction in PSA | Proportion of Patients with at least 25% decline in PSA on Day 1 of Cycle 2, Day 1 of Cycle 3, and on day of radical prostatectomy. | One patient did not have lab samples collected on day of radical prostatectomy. | Posted | Count of Participants | Participants | Day 1 of cycles 2 and 3 and on the day of radical prostatectomy. Each cycle is 2 weeks. |
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Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 113
If a subject experienced more than 1 of a given AE, the subject is counted only once for that AE.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 48 Hour Drug Stop Point | Sorafenib 400mg taken orally twice per day for 41 days prior to radical prostatectomy. Last dose of study drug is the morning dose 2 days prior to surgery. | 0 | 5 | 5 | 5 | ||
| EG001 | 24 Hour Drug Stop Point | Sorafenib 400mg taken orally twice per day for 42 days prior to radical prostatectomy. Last dose of study drug is the morning dose the day prior to surgery. | 0 | 0 | 0 | 0 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Tinnitus | Ear and labyrinth disorders | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | Systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
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| pain, gastrointestinal, oral cavity, esophagus | General disorders | Systematic Assessment |
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| pain, renal/genitourinary | General disorders | Systematic Assessment |
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| Fatigue | General disorders | Systematic Assessment |
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| Weight loss | General disorders | Systematic Assessment |
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| Pancreatitis | Hepatobiliary disorders | Systematic Assessment |
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| Transaminitis | Metabolism and nutrition disorders | Systematic Assessment |
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| pain, musculoskeletal, extremity-limb | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Tingling feet and scalp | Nervous system disorders | Systematic Assessment |
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| Urinary retention | Renal and urinary disorders | Systematic Assessment |
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| urination frequency and urgency | Renal and urinary disorders | Systematic Assessment |
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| Gynecomastia | Reproductive system and breast disorders | Systematic Assessment |
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| voice changes/dysarthria | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Alopecia | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Dry skin | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Hand-foot syndrome | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Pruritis | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Hypertension | Vascular disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Evan Yu | University of Washington / Seattle Cancer Care Alliance | 206-288-1152 | evanyu@u.washington.edu |
| ID | Term |
|---|---|
| D011471 | Prostatic Neoplasms |
| ID | Term |
|---|---|
| D005834 | Genital Neoplasms, Male |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D005832 | Genital Diseases, Male |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D011469 | Prostatic Diseases |
| D052801 | Male Urogenital Diseases |
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| ID | Term |
|---|---|
| D000077157 | Sorafenib |
| D046228 | Microarray Analysis |
| D020869 | Gene Expression Profiling |
| D007150 | Immunohistochemistry |
| D001707 | Biopsy, Needle |
| D015153 | Blotting, Western |
| ID | Term |
|---|---|
| D010671 | Phenylurea Compounds |
| D014508 | Urea |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009536 | Niacinamide |
| D009539 | Nicotinic Acids |
| D000147 | Acids, Heterocyclic |
| D006571 | Heterocyclic Compounds |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D046208 | Microchip Analytical Procedures |
| D008919 | Investigative Techniques |
| D005821 | Genetic Techniques |
| D006651 | Histocytochemistry |
| D003584 | Cytological Techniques |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D006652 | Histological Techniques |
| D007158 | Immunologic Techniques |
| D001706 | Biopsy |
| D003581 | Cytodiagnosis |
| D013048 | Specimen Handling |
| D003949 | Diagnostic Techniques, Surgical |
| D013514 | Surgical Procedures, Operative |
| D011677 | Punctures |
| D004586 | Electrophoresis |
| D002623 | Chemistry Techniques, Analytical |
| D055664 | Electrochemical Techniques |
| D015151 | Immunoblotting |
| D007118 | Immunoassay |
| D015336 | Molecular Probe Techniques |
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| >=65 years |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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