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

Stopped early · Phase 1

Conditions studied: Cancer

In brief

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 The investigators' gene array data predict sensitivity to valproic acid in over half of breast cancers \[Bild, unpublished\].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.

Key facts

Study ID

NCT01007695

Run by

University of Utah

People needed

31

Starts

2010-05-01

Expected to finish

2015-05-01

Last updated by the study team

2016-07-20

Who can join

Age: 18 and older. Sex: female. Healthy volunteers: not accepted.

You may qualify if…

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

You may not qualify if…

• 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.
• Known hypersensitivity to valproic acid or its components or peanut allergy
• Inadequate bone marrow, kidney, and liver function (greater than grade 1 by CTCAE version 4) as defined by the protocol.
• Immunocompromised due to medications or HIV as documented in medical history
• Use of other antiepileptics or medications with known interactions with valproic acid (See protocol for full list)
• Inborn errors of metabolism (valproic acid is contraindicated in patients with known urea cycle disorders)
• History of pancreatitis
• Use of a ketogenic diet
• 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
• Tumor that is unlikely to yield adequate tissue for genomic studies in the opinion of the principle investigator

Where it is running

• Huntsman Cancer Institute — Salt Lake City, Utah, United States

Full record on ClinicalTrials.gov

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