Impact of Valproate on Angiogenesis and Histone Deacetylation in Bladder Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2012 by State University of New York - Upstate Medical University
Sponsor:
Information provided by (Responsible Party):
State University of New York - Upstate Medical University
ClinicalTrials.gov Identifier:
NCT01738815
First received: November 28, 2012
Last updated: December 12, 2012
Last verified: December 2012
  Purpose

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


Condition Intervention Phase
Hematuria
Bladder Cancer
Drug: Valproic Acid
Phase 0

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Impact of Valproate on Angiogenesis and Histone Deacetylation in Bladder Cancer

Resource links provided by NLM:


Further study details as provided by State University of New York - Upstate Medical University:

Primary Outcome Measures:
  • Thrombospondin-1 gene expression [ Time Frame: 1 day ] [ Designated as safety issue: No ]
    Expression of thrombospondin-1 will be assayed using quantitative real-time PCR and western blotting. Comparisons will be intra-patient for paired specimens acquired prior to and after treatment and inter-patient for treated and un-treated patients.


Secondary Outcome Measures:
  • Angiogenesis, proliferation, and histone deacetylase activity markers [ Time Frame: 1 day ] [ Designated as safety issue: No ]
    Histone deacetylase activity, angiogenesis, and proliferation markers will be assayed using qPCR and western blotting of tumor biopsy specimens. Comparisons will be intra-patient for paired specimens acquired prior to and after treatment and inter-patient for treated and un-treated patients.


Estimated Enrollment: 50
Study Start Date: December 2011
Estimated Study Completion Date: May 2013
Estimated Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: valproic acid
Patients will be administered valproic acid (Depakote ER) for up to 30 days prior to tumor resection
Drug: Valproic Acid
500 mg orally, once daily for up to 30 days
Other Name: Depakote ER

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.

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01738815

Locations
United States, New York
SUNY Upstate Medical University Recruiting
Syracuse, New York, United States, 13210
Contact: Jay E Reeder, Ph.D.    315-464-6104    reederj@upstate.edu   
Contact: Barbara McConnell    315-464-4473    mcconneb@upstate.edu   
Principal Investigator: Oleg Shapiro, M.D.         
Principal Investigator: Gennady Bratslavsky, M.D.         
Sub-Investigator: Jay E Reeder, Ph.D.         
Sponsors and Collaborators
State University of New York - Upstate Medical University
Investigators
Principal Investigator: Oleg Shapiro, MD State University of New York - Upstate Medical University
  More Information

No publications provided

Responsible Party: State University of New York - Upstate Medical University
ClinicalTrials.gov Identifier: NCT01738815     History of Changes
Other Study ID Numbers: 256549
Study First Received: November 28, 2012
Last Updated: December 12, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by State University of New York - Upstate Medical University:
bladder cancer
hematuria
sodium valproate
valproic acid

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Hematuria
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Urination Disorders
Hemorrhage
Pathologic Processes
Valproic Acid
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
GABA Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs

ClinicalTrials.gov processed this record on October 19, 2014