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

Sponsor:	University of California, Los Angeles
Collaborator:	Pfizer
Information provided by:	University of California, Los Angeles
ClinicalTrials.gov Identifier:	NCT00790595

Purpose

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.

Condition	Intervention	Phase
Prostate Cancer	Drug: SU011248	Phase I

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:	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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Prostate Cancer

Drug Information available for: Sunitinib malate Sunitinib

U.S. FDA Resources

Further study details as provided by University of California, Los Angeles:

Primary Outcome Measures:

To evaluate the effects of SU011248 by histological examination of prostate tumors following radical prostatectomy and determine the safety and maximum tolerable dose of SU011248 when administered with prostate cancer prior to radical prostatectomy. [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To evaluate the effects of SU011248 on tumoral phospho VEGF/PDGF, receptor TK pathways, microvessel density, antiangiogenic activities, other known biological targets of Sunitinib activity and evaluate the effect of SU011248 on serum PSA levels. [ Time Frame: 24 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	25
Study Start Date:	September 2006
Estimated Primary Completion Date:	September 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Group A: Experimental 5 Subjects will receive 37.5 mg/d of the study drug for 1 week.	Drug: SU011248 5 Subjects will receive 37.5 mg/d of the study drug for 1 week.
Group B: Experimental 5 Subjects will receive 50.0 mg/d of the study drug for 1 week.	Drug: SU011248 5 Subjects will receive 50.0 mg/d of the study drug for 1 week.
Group C: Experimental 5 Subjects will receive 37.5 mg/d of the study drug for 2 weeks.	Drug: SU011248 5 Subjects will receive 37.5 mg/d of the study drug for 2 weeks.
Group D: Experimental 5 Subjects will receive 50.0 mg/d of the study drug for 2 weeks.	Drug: SU011248 5 Subjects will receive 50.0 mg/d of the study drug for 2 weeks.
Group E: Experimental 5 Subjects will receive 50.0 mg/d of the study drug for 4 weeks.	Drug: SU011248 5 Subjects will receive 50.0 mg/d of the study drug for 4 weeks.

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Criteria

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 oxaloactic 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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00790595

Contacts

Contact: Robert La Ferte

310-267-2336

rlaferte@mednet.ucla.edu

Locations

United States, California
University of California, Los Angeles, Jonsson Comprehensive Cancer Center	Recruiting
Los Angeles, California, United States, 90095
Contact: Robert La Ferte 310-267-2336
Sub-Investigator: Allan Pantuck, M.D.
Sub-Investigator: Robert Reiter, MD
Sub-Investigator: Mark Litwin, MD
Sub-Investigator: Jean deKernion, MD
Sub-Investigator: Matthew Rettig, MD
Sub-Investigator: Steven Riggs, MD

Sponsors and Collaborators

University of California, Los Angeles

Pfizer

Investigators

Principal Investigator:

Arie Belldegrun, M.D.

University of California, Los Angeles

More Information

Publications:

Weir HK, Thun MJ, Hankey BF, Ries LA, Howe HL, Wingo PA, Jemal A, Ward E, Anderson RN, Edwards BK. Annual report to the nation on the status of cancer, 1975-2000, featuring the uses of surveillance data for cancer prevention and control. J Natl Cancer Inst. 2003 Sep 3;95(17):1276-99. Review. Erratum in: J Natl Cancer Inst. 2003 Nov 5;95(21):1641.

Pound CR, Partin AW, Eisenberger MA, Chan DW, Pearson JD, Walsh PC. Natural history of progression after PSA elevation following radical prostatectomy. JAMA. 1999 May 5;281(17):1591-7.

Roehl KA, Han M, Ramos CG, Antenor JA, Catalona WJ. Cancer progression and survival rates following anatomical radical retropubic prostatectomy in 3,478 consecutive patients: long-term results. J Urol. 2004 Sep;172(3):910-4.

Kasamon KM, Dawson NA. Update on hormone-refractory prostate cancer. Curr Opin Urol. 2004 May;14(3):185-93. Review.

Zagars GK. Prostate-specific antigen as a prognostic factor for prostate cancer treated by external beam radiotherapy. Int J Radiat Oncol Biol Phys. 1992;23(1):47-53.

Stamey TA, Kabalin JN, Ferrari M. Prostate specific antigen in the diagnosis and treatment of adenocarcinoma of the prostate. III. Radiation treated patients. J Urol. 1989 May;141(5):1084-7.

Kabalin JN, Hodge KK, McNeal JE, Freiha FS, Stamey TA. Identification of residual cancer in the prostate following radiation therapy: role of transrectal ultrasound guided biopsy and prostate specific antigen. J Urol. 1989 Aug;142(2 Pt 1):326-31.

Zagars GK, von Eschenbach AC, Johnson DE, Oswald MJ. Stage C adenocarcinoma of the prostate. An analysis of 551 patients treated with external beam radiation. Cancer. 1987 Oct 1;60(7):1489-99.

Bagshaw MA, Cox RS, Ramback JE. Radiation therapy for localized prostate cancer. Justification by long-term follow-up. Urol Clin North Am. 1990 Nov;17(4):787-802.

Wheeler JA, Zagars GK, Ayala AG. Dedifferentiation of locally recurrent prostate cancer after radiation therapy. Evidence for tumor progression. Cancer. 1993 Jun 1;71(11):3783-7.

Cumming JA, Ritchie AW, Goodman CM, McIntyre MA, Chisholm GD. De-differentiation with time in prostate cancer and the influence of treatment on the course of the disease. Br J Urol. 1990 Mar;65(3):271-4.

Stamey TA and McNeal JE: Adenocarcinoma of the prostate. In Campbell's Urology 6th edition (Walsh PC, Retik AB, Stamey MA and Vaughan ED, eds), W.B. Saunders Co., pp 1159-1221, 1992.

Stamey TA, Villers AA, McNeal JE, Link PC, Freiha FS. Positive surgical margins at radical prostatectomy: importance of the apical dissection. J Urol. 1990 Jun;143(6):1166-72; discussion 1172-3.

Rosen MA, Goldstone L, Lapin S, Wheeler T, Scardino PT. Frequency and location of extracapsular extension and positive surgical margins in radical prostatectomy specimens. J Urol. 1992 Aug;148(2 Pt 1):331-7.

Catalona WJ, Bigg SW. Nerve-sparing radical prostatectomy: evaluation of results after 250 patients. J Urol. 1990 Mar;143(3):538-43; discussion 544.

Stein A, deKernion JB, Dorey F. Prostatic specific antigen related to clinical status 1 to 14 years after radical retropubic prostatectomy. Br J Urol. 1991 Jun;67(6):626-31.

Frazier HA, Robertson JE, Humphrey PA, Paulson DF. Is prostate specific antigen of clinical importance in evaluating outcome after radical prostatectomy. J Urol. 1993 Mar;149(3):516-8.

Responsible Party:	UCLA ( Arie Belldegrun, M.D. )
Study ID Numbers:	06-03-129, Pfizer2005-0958
Study First Received:	November 12, 2008
Last Updated:	November 12, 2008
ClinicalTrials.gov Identifier:	NCT00790595 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by University of California, Los Angeles:

Prostatectomy

Additional relevant MeSH terms:

Genital Neoplasms, Male
Prostatic Diseases
Antineoplastic Agents
Growth Substances
Physiological Effects of Drugs
Urogenital Neoplasms
Genital Diseases, Male
Angiogenesis Inhibitors

Pharmacologic Actions
Neoplasms
Neoplasms by Site
Sunitinib
Therapeutic Uses
Growth Inhibitors
Angiogenesis Modulating Agents
Prostatic Neoplasms

ClinicalTrials.gov processed this record on February 08, 2010