- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01738815
Impact of Valproate on Angiogenesis and Histone Deacetylation in Bladder Cancer
October 19, 2021 updated by: 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.
Study Overview
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.
Study Type
Interventional
Enrollment (Actual)
43
Phase
- Early Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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New York
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Syracuse, New York, United States, 13210
- SUNY Upstate Medical University
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
19 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Patient over the age of 21
- Bladder tumor suspected or confirmed
- ECOG status 0 to 2
- 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:
- Allergy to valproic acid
- Concurrent chemotherapy
- Pre-menopausal women
- Active systemic infection (HepatitisB,C)
- Coagulation disorders
- Concurrent medication: Tolbutamide, Warfarin, Zidovudine, Benzodiazepine, Clonazepam, Diazepam, Any anti-convulsant therapy
- Seizure disorder
- Dementia
- History of Pancreatitis
- HIV diagnosis/treatment
- Liver disease/dysfunction
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: valproic acid
Patients will be administered valproic acid (Depakote ER) for up to 30 days prior to tumor resection
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500 mg orally, once daily for up to 30 days
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Thrombospondin-1 gene expression
Time Frame: 1 day
|
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.
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1 day
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Angiogenesis, proliferation, and histone deacetylase activity markers
Time Frame: 1 day
|
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.
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1 day
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Oleg Shapiro, MD, State University of New York - Upstate Medical University
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
December 1, 2011
Primary Completion (Actual)
May 1, 2013
Study Completion (Actual)
April 1, 2014
Study Registration Dates
First Submitted
November 28, 2012
First Submitted That Met QC Criteria
November 29, 2012
First Posted (Estimate)
November 30, 2012
Study Record Updates
Last Update Posted (Actual)
October 22, 2021
Last Update Submitted That Met QC Criteria
October 19, 2021
Last Verified
October 1, 2021
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Neoplasms
- Urologic Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Urologic Diseases
- Urinary Bladder Diseases
- Hemorrhage
- Urination Disorders
- Urinary Bladder Neoplasms
- Hematuria
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Enzyme Inhibitors
- Tranquilizing Agents
- Psychotropic Drugs
- GABA Agents
- Anticonvulsants
- Antimanic Agents
- Valproic Acid
Other Study ID Numbers
- 256549
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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