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Molecular Signature of Valproic Acid in Breast Cancer With Functional Imaging Assessment - a Pilot (VAST)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01007695
Recruitment Status : Terminated (Enrollment was going slowly and needed to be closed.)
First Posted : November 4, 2009
Last Update Posted : July 20, 2016
Information provided by (Responsible Party):
University of Utah

Brief Summary:
The investigators' hypothesis is that valproic acid given before surgery for newly diagnosed breast cancer will increase breast tumor histone acetylation at tolerable doses and that the increase in breast tumor histone acetylation will correlate with valproic acid blood levels and changes in peripheral blood white blood cell histone acetylation. Published in vitro studies have shown sensitivity of breast cancer cells to histone deacetylase inhibitors (Fortunati et al., 2008; Fuino et al., 2003; Hodges-Gallagher et al., 2007; Olsen et al., 2004). The investigators' gene array data predict sensitivity to valproic acid in over half of breast cancers [Bild, unpublished]. The investigators hypothesize that in women with newly diagnosed breast cancers valproic acid will have an unacceptable toxicity rate less than 15% at doses that increase tumor histone acetylation and that valproic acid will decrease the Ki-67 in at least half of breast tumors by over 20%. The investigators also hypothesize that their genomically-derived signature for sensitivity to valproic acid (GDSS-VPA) can be used to predict which tumors will have a decrease proliferation as measured by Ki-67 by at least 20%. The investigators hypothesize that valproic acid levels and histone acetylation levels in peripheral leukocytes will correlate with a decrease in the Ki-67 proliferation index by 20%. The investigators hypothesize that DCE-MRI imaging studies will provide an accurate and quantitative means of assessing tumor response to valproic acid. Finally, the investigators hypothesize that response to valproic acid will not be affected by intrinsic breast cancer subtype.

Condition or disease Intervention/treatment Phase
Cancer Drug: Valproic Acid Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 31 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Molecular Signature of Valproic Acid in Breast Cancer With Functional Imaging Assessment - a Pilot
Study Start Date : May 2010
Actual Primary Completion Date : May 2015
Actual Study Completion Date : May 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: All patients
All participants enrolled.
Drug: Valproic Acid
Valproic Acid is FDA approved and indicated as monotherapy and adjunctive therapy in the treatment of patients with complex partial seizures that occur either in isolation or in association with other types of seizures. Valproic Acid is indicated for use as sole and adjunctive therapy in the treatment of simple and complex absence seizures, and adjunctively in patients with multiple seizure types which include absence seizures.

Primary Outcome Measures :
  1. Determine if valproic acid levels correlate with histone acetylation in leukocytes during treatment and whether either valproic acid levels or histone acetylation in leukocytes predict histone acetylation in tumor samples post treatment. [ Time Frame: December 2013 ]

Secondary Outcome Measures :
  1. Assess the sensitivity and specificity of the genomic sensitivity signature of VPA (GDSS-VPA) to predict histologically measured antitumor activity of valproic acid in newly diagnosed breast cancer. [ Time Frame: December, 2013 ]
  2. Analyze the change in immunohistochemical markers of proliferation, apoptosis, and tumor grade following treatment with valproic acid in newly diagnosed breast cancer. [ Time Frame: December, 2013 ]
  3. Analyze the change in radiologic markers of tumor size and vascularity following treatment with valproic acid in newly diagnosed breast cancer [ Time Frame: December, 2013 ]
  4. Analyze whether intrinsic breast subtype by the Breast Bioclassifier correlates with changes in tumor proliferation rate or changes in DCE-MRI markers of size and vascularity following treatment with valproic acid. [ Time Frame: December, 2013 ]
  5. Determine if women have dose-limiting toxicities for valproic acid over 7-12 days [ Time Frame: December, 2013 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Biopsy-proven invasive adenocarcinoma of the breast 1.5cm or larger by clinical exam or imaging including ultrasound, mammogram, CT, or MRI
  2. Females at least 18 years-old,
  3. Not pregnant, as demonstrated by a negative serum or urine pregnancy test in women of child bearing potential, and not planning on becoming pregnant
  4. Willing to have a biopsy at the start of study if adequate sample for gene array is not available.
  5. Willing to have a biopsy at the end of the trial if breast surgery is not planned.
  6. ECOG Performance status 0-2
  7. Able to provide informed consent and have signed an approved consent form that conforms to federal and institutional guidelines

Exclusion Criteria:

  1. Need for immediate chemotherapy as determined by the patients' physicians, e.g., present or imminent compromise of vital organs or unacceptable symptoms from the tumor.
  2. Known hypersensitivity to valproic acid or its components or peanut allergy
  3. Inadequate bone marrow, kidney, and liver function (greater than grade 1 by CTCAE version 4) as defined by the protocol.
  4. Immunocompromised due to medications or HIV as documented in medical history
  5. Use of other antiepileptics or medications with known interactions with valproic acid (See protocol for full list)
  6. Inborn errors of metabolism (valproic acid is contraindicated in patients with known urea cycle disorders)
  7. History of pancreatitis
  8. Use of a ketogenic diet
  9. Inability to have an MRI due to extreme claustrophobia, possible metal fragments in the eye, cardiac pacemaker, implanted cardiac defibrillator, aneurysm clips, carotid artery vascular clamp, neurostimulator, insulin or infusion pump, implanted drug infusion device, bone growth/fusion stimulator, or cochlear, otologic, or ear implant
  10. Tumor that is unlikely to yield adequate tissue for genomic studies in the opinion of the principle investigator

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01007695

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United States, Utah
Huntsman Cancer Institute
Salt Lake City, Utah, United States, 84112
Sponsors and Collaborators
University of Utah
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Principal Investigator: Theresa Werner, MD Huntsman Cancer Institute
Study Chair: Adam Cohen, MD Huntsman Cancer Institute
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Responsible Party: University of Utah Identifier: NCT01007695    
Other Study ID Numbers: HCI36488
First Posted: November 4, 2009    Key Record Dates
Last Update Posted: July 20, 2016
Last Verified: July 2016
Keywords provided by University of Utah:
breast cancer
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Valproic Acid
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