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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by University of Utah
Sponsor:
Information provided by (Responsible Party):
University of Utah
ClinicalTrials.gov Identifier:
NCT01007695
First received: November 2, 2009
Last updated: July 2, 2014
Last verified: July 2014
  Purpose

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 The investigators' gene array data predict sensitivity to valproic acid in over half of breast cancers [Bild, unpublished].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 Intervention Phase
Cancer
Drug: Valproic Acid
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Molecular Signature of Valproic Acid in Breast Cancer With Functional Imaging Assessment - a Pilot

Resource links provided by NLM:


Further study details as provided by University of Utah:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Determine if women have dose-limiting toxicities for valproic acid over 7-12 days [ Time Frame: December, 2013 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 33
Study Start Date: May 2010
Estimated Study Completion Date: May 2016
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT01007695

Contacts
Contact: Mark Wade 801-587-4284 mark.wade@hci.utah.edu
Contact: Greg Lamb 801-585-0431 greg.lamb@hci.utah.edu

Locations
United States, Utah
Huntsman Cancer Institute Recruiting
Salt Lake City, Utah, United States, 84112
Sponsors and Collaborators
University of Utah
Investigators
Principal Investigator: Theresa Werner, MD Huntsman Cancer Institute
Study Chair: Adam Cohen, MD Huntsman Cancer Institute
  More Information

No publications provided

Responsible Party: University of Utah
ClinicalTrials.gov Identifier: NCT01007695     History of Changes
Other Study ID Numbers: HCI36488
Study First Received: November 2, 2009
Last Updated: July 2, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by University of Utah:
breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
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 01, 2014