Clinical Study of SU011248 in Subjects With High Risk Prostate Cancer Who Have Elected to Undergo Radical Prostatectomy

Study Overview
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Brief Summary
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Prostate cancer is prevalent in the United States, with approximately 230,110 new cases and 29,900 deaths in 2004. Approximately 30% of new cases will be clinical stage T3 when they are diagnosed. This is a stage in which there is high probability that the cancer has spread beyond the prostate gland itself, making it much more difficult to treat. In these cases, when surgery is done by itself and the prostate is removed, it is still very likely that some cancer that has spread beyond the prostate remains and will get worse. Radiation applied to the prostate also does not work well on tumors that have spread beyond the prostate. Even surgery and radiation combined have not eliminated the problems caused by prostate cancer that has spread into the tissue outside the prostate itself. New treatments are needed to deal with prostate cancer at this more serious stage. Study doctors believe that it might be possible to shrink the prostate cancer using a new drug called SUO11248 or Sunitinib. After the patients take the drug, study doctors believe the cancer will shrink back to within the prostate, and they can then surgically remove the prostate and all the cancer. Patients on this study also will be given increasing doses of Sunitinib to find out how much of the drug can be given safely.

Official Title
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Phase I, Open Label, Single Center, Multiple Dose, Dose Escalation Clinical Study of SU011248 in Subjects With High Risk Prostate Cancer Who Have Elected to Undergo Radical Prostatectomy

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: SU011248
* Drug: SU011248
* Drug: SU011248
* Drug: SU011248
* Drug: SU011248


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed adenocarcinoma of the prostate glad. Informed of, willing, and able to comply with, the requirements of the investigational study and have signed a written informed consent in accordance with institutional regulatory guidelines. Subjects defined as being at high risk for disease relapse based on the following criteria: PSA > 10 ng/ml, and any one of the following: Gleason > 7 or T stage > T2b. Patients must have elected to and are a candidate to undergo a radical prostatectomy. Males greater than 18 years of age and less than or equal to 75 years of age (physiologic) any racial/ethnic group. Free of significant abnormal findings as determined by screening history, physical exam, vital signs (blood pressure, heart rate, respiration rate, and temperature), and urinalysis. Performance status: ECOG < 2. Life expectancy of at least 5 years. Absolute granulocyte count > 1,500/mm3. Platelet count > 100,000. Hemoglobin > 9.0 g/dL. Serum calcium < 12.0 mg/dL Adequate hepatic function as evidenced by ALT and AST values within normal range. Adequate organ function as defined by the following criteria: Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase [SGOT]) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase [SGPT]) < 2.5 x local laboratory upper limit of normal (ULN), or AST and ALT < 5 x ULN if liver function abnormalities are due to underlying malignancy. Creatinine < 1.5 ULN. Exclusion Criteria: Patients who have stage T2a or less prostate cancer, Gleason < 6, PSA <10-ng/mL. Prior hormonal, surgical, radiopharmaceutical or radiation therapy, cryotherapy, biological response modifiers, or systematic chemotherapy to treat prostatic carcinoma. Surgery within four weeks of study entry. Evidence of regional and/or distant metastases. Use of an investigational drug within 30 days prior to study entry. NCI CTCAE Version 3.0 grade 3 hemorrhage within 4 weeks of starting the study treatment. Any of the following thing the 12 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism. Ongoing cardiac dysrhythmias of NCI CTCAE Version 3.0 grade > 2. Prolonged QTc interval on baseline EKG. Uncontrolled Hypertension (>150/100 mm Hg despite optimal medical therapy). Patients receiving CYP3A4 inducers or inhibitors; patients should not take grapefruit juice or St. John's Wort while on the study Known active infection.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>5 Subjects will receive 37.5 mg/d of the study drug for 1 week. | Drug: SU011248<br>* 5 Subjects will receive 37.5 mg/d of the study drug for 1 week.<br>|
| Experimental: Group B<br>5 Subjects will receive 50.0 mg/d of the study drug for 1 week. | Drug: SU011248<br>* 5 Subjects will receive 50.0 mg/d of the study drug for 1 week.<br>|
| Experimental: Group C<br>5 Subjects will receive 37.5 mg/d of the study drug for 2 weeks. | Drug: SU011248<br>* 5 Subjects will receive 37.5 mg/d of the study drug for 2 weeks.<br>|
| Experimental: Group D<br>5 Subjects will receive 50.0 mg/d of the study drug for 2 weeks. | Drug: SU011248<br>* 5 Subjects will receive 50.0 mg/d of the study drug for 2 weeks.<br>|
| Experimental: Group E<br>5 Subjects will receive 50.0 mg/d of the study drug for 4 weeks. | Drug: SU011248<br>* 5 Subjects will receive 50.0 mg/d of the study drug for 4 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the effects of SU011248 by histological examination of prostate tumors following radical prostatectomy. |  | 24 months | 
| To determine maximum tolerable dose of SU011248 when administered with prostate cancer prior to radical prostatectomy. |  | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the effects of SUO11248 on tumoral phospho VEGF/PDGF, receptor TK pathways, microvessel density, antiangiogenic activities and serum PSA levels. |  | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prostatectomy