Valproic Acid in Combination With FEC100 for Primary Therapy in Patients With Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: VPA FEC100
Intervention description: oral VPA (60 mg/kg bid) q 12h X 6 with IV 5-Fluorouracil (500 mg/m2) Epirubicin (100 mg/m2) and Cyclophosphamide (500 mg/m2)
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: breast cancer; advanced; local

Summary:

      The drugs FEC 100 (5-fluorouracil, epirubicin, and cyclophosphamide) are one of the approved
      options to treat Locally Advanced or Primary Metastatic Breast Cancer. In this study, the
      investigators will add another drug called Valproic Acid (VPA) to see whether this makes the
      treatment better. The addition of Valproic Acid to chemotherapy has been studied in about 65
      subjects with cancer and was found to be safe and tolerable. Valproic Acid is approved by the
      Food and Drug Administration (FDA) for the treatment of seizures, mood swings, and migraine
      headaches. It is not currently approved for cancer, which is why the investigators are
      conducting this study.

      The results of a Phase I study of Valproic Acid and FEC100 in subjects with cancer that has
      spread has led the investigators to believe that this combination is better than just the
      standard treatment alone. The investigators are now testing the combination in a study with
      subjects who have either a large tumor, many lymph nodes involved or patients whose tumor has
      spread. In addition to the treatment, a main goal of the study is to find out which subjects
      will benefit from this combination. In the Phase I trial the investigators noticed that while
      this combination appears to make the chemotherapy more effective, it did not appear to cause
      more side effects induced by the chemotherapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed diagnosis of breast
             cancer

          -  Patients must have "locally advanced" adenocarcinoma of the breast:

               -  tumors > 2 cm without lymph node involvement (negative sentinel lymph node
                  mapping)

               -  tumors > 2 cm with lymph node involvement (either by positive sentinel lymph node
                  mapping or FNA of palpable lymph node)

               -  tumors of any size that show extension to the chest wall or skin, including
                  edema, ulceration, or satellite skin nodules

               -  inflammatory carcinoma (stage IIIB) that is amenable to surgery

               -  tumors of any size associated with ipsilateral internal mammary nodes (stage
                  IIIB)

               -  tumors of any size associated with ipsilateral supraclavicular lymph nodes (IIIC)
                  without other evidence of systemic metastases

               -  patients may have bilateral breast cancer if both breasts are assessible for
                  response

          -  Age >18 years

          -  Because no dosing or adverse event data are currently available on the use of VPA in
             combination with FEC100 in patients <18 years of age, children are excluded from this
             study

          -  ECOG performance status 0 or 1 (Karnofsky >80%)

          -  Patients must have normal organ and marrow function as defined below:

               -  leukocytes >3,000/mcL

               -  absolute neutrophil count >1,500/mcL

               -  platelets >100,000/mcL

               -  total bilirubin within 1.5 x normal institutional limits

               -  AST(SGOT)/ALT(SGPT) <2.5 X institutional upper limit of normal

               -  Creatinine within normal institutional limits

          -  VPA has been associated with neural tube defects in the developing human fetus, for
             this reason and because FEC100 used in this trial are also known to be teratogenic,
             women of child-bearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control; abstinence) prior to study entry and for
             the duration of study participation. Participating men must use condoms while on study
             and for at least 3 months after the trial has ended. Should a woman become pregnant or
             suspect she is pregnant while participating in this study, she should inform her
             treating physician immediately.

          -  Ability to understand and the willingness to sign a written informed consent document.

        Exclusion Criteria:

          -  Patients may not have had any prior chemotherapy within the last 2 years

          -  Patients may not have been exposed to prior anthracyclines

          -  Patients may not be receiving any other investigational agents

          -  Patients with known brain metastases are excluded

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to VPA or FEC100.

          -  Patients with known congestive heart disease or LVEF fractions of <50 % (past or
             current), patients with known ventricular arrhythmias

          -  Patients taking VPA as an anti-seizure agent or for any other indications

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  Due to the teratogenic effects of VPA and FEC100, pregnant or lactating women are
             excluded from the study.