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Impact of Valproate on Angiogenesis and Histone Deacetylation in Bladder Cancer

Information source: State University of New York - Upstate Medical University
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Hematuria; Bladder Cancer

Intervention: Valproic Acid (Drug)

Phase: Phase 0

Status: Recruiting

Sponsored by: State University of New York - Upstate Medical University

Official(s) and/or principal investigator(s):
Oleg Shapiro, MD, Principal Investigator, Affiliation: State University of New York - Upstate Medical University


The goal of this study is to test whether the drug valproic acid can cause changes in bladder tumors that might inhibit their growth.

Clinical Details

Official title: Impact of Valproate on Angiogenesis and Histone Deacetylation in Bladder Cancer

Study design: Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Primary outcome: Thrombospondin-1 gene expression

Secondary outcome: Angiogenesis, proliferation, and histone deacetylase activity markers

Detailed description: Bladder cancer is the fourth most common cancer in the United States with over 60,000 new cases each year. It can usually be treated initially by insertion of an endoscope into the bladder and surgically removing the tumor, a procedure known as cystoscopy and trans-urethral resection of bladder tumor (TURBT). For most patients this procedure will successfully remove all of the detectable tumor. Unfortunately over 40% of all patients will develop a cancer recurrence in less than two years and all patients remain at increased risk of recurrence for the remainder of their lives. This risk requires life long monitoring and this is best accomplished with regular cystoscopic examinations. The goal of this study is to test whether the drug valproic acid can cause changes in bladder tumors that might inhibit their growth. Patients with suspected bladder cancer will be invited to participate in the study, if a tumor is observed during cystoscopy it will be sampled for research purposes and then according to standards of care, the patient scheduled for TURBT under general anesthesia. In the interval between discovery of a bladder tumor and resection, usually two to four weeks, the patient will be given valproic acid to take orally. In addition, tumors from patients with known or suspected bladder cancer referred for TURBT or cystectomy will be sampled. The tumor pieces obtained before and after taking valproic acid and from the referral patients not treated with valproic acid will be analyzed to see if the drug has changed what genes are active. We have found that valproic acid causes bladder cancer cells to make more of the protein, thrombospondin-1. This protein inhibits the growth of new blood vessels and so increased thrombospondin-1 in bladder tumors should inhibit their growth by decreasing the blood supply. Valproic acid may change thrombospondin-1 levels through inhibition of histone deacetylases. We will also assay HDAC activity in the tumor specimens. If valproic acid alters thrombospondin-1 levels and HDAC activity in bladder cancer patients further study to see if it can reduce growth will be justified. Valproic acid is a drug approved for the treatment of seizure disorders that is generally well tolerated with few side effects. It may prove useful in reducing bladder cancer recurrence and progression.


Minimum age: 21 Years. Maximum age: N/A. Gender(s): Both.


Inclusion Criteria: 1. Patient over the age of 21 2. Bladder tumor suspected or confirmed 3. ECOG status 0 to 2 4. Premedication Lab values: Absolute Neutrophil Count >750 cells/m3 AST/ALT less than 1. 5xN Amylase less than 1. 5xN Platelet Count > 125,000 PT/PTT > 1. 3xN Hemoglobin > 8gm/dL Creatinine less than 1. 5xN Exclusion Criteria: 1. Allergy to valproic acid 2. Concurrent chemotherapy 3. Pre-menopausal women 4. Active systemic infection (HepatitisB,C) 5. Coagulation disorders 6. Concurrent medication: Tolbutamide, Warfarin, Zidovudine, Benzodiazepine, Clonazepam, Diazepam, Any anti-convulsant therapy 7. Seizure disorder 8. Dementia 9. History of Pancreatitis 10. HIV diagnosis/treatment 11. Liver disease/dysfunction

Locations and Contacts

SUNY Upstate Medical University, Syracuse, New York 13210, United States; Recruiting
Jay E Reeder, Ph.D., Phone: 315-464-6104, Email: reederj@upstate.edu
Barbara McConnell, Phone: 315-464-4473, Email: mcconneb@upstate.edu
Oleg Shapiro, M.D., Principal Investigator
Gennady Bratslavsky, M.D., Principal Investigator
Jay E Reeder, Ph.D., Sub-Investigator
Additional Information

Starting date: December 2011
Last updated: December 12, 2012

Page last updated: August 20, 2015

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