A Pre-Surgical PK Study of IM and Intraductally Delivered Fulvestrant
Condition: Female Breast Carcinoma; Female Ductal Carcinoma In Situ
MeSH terms: Carcinoma; Breast Neoplasms; Carcinoma in Situ; Carcinoma, Ductal; Carcinoma, Intraductal, Noninfiltrating
Intervention: Fulvestrant
Intervention MeSH terms: Fulvestrant
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is an open-label, non-randomized pharmacokinetic study of fulvestrant in women scheduled
      for mastectomy or lumpectomy. Eligible subjects will be identified with breast cancer or
      DCIS. The first subject of each of five groups will receive fulvestrant intramuscularly. The
      subsequent 5 subjects of each group will receive fulvestrant by intraductal instillation. All
      subjects will be monitored for systemic and local adverse events during the procedure, and
      following the procedure until mastectomy or lumpectomy. Subjects that receive fulvestrant
      will undergo serial blood draws to determine fulvestrant blood concentration levels.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Female

          2. 18 years of age or older

          3. Scheduled to undergo non-nipple sparing mastectomy for Invasive Breast Cancer or DCIS

          4. Pathological diagnosis of Invasive Ductal Breast Cancer or Ductal Carcinoma in Situ
             requiring mastectomy or lumpectomy

          5. Estrogen Receptor-positive pathology

          6. ECOG performance scale of 0-1

          7. Adequate organ function as defined by the following criteria:

               -  Absolute neutrophil count (ANC) ≥ 1500/μl

               -  Platelets ≥ 100,000/μl

               -  Hemoglobin ≥ 9.0 g/dl

               -  Creatinine ≤ 2 times upper limit of normal

               -  Bilirubin ≤ 2 times upper limit of normal

               -  Transaminases (AST/SGOT and ALT/SGPT) ≤ 2.5 times upper limit of normal

          8. Able to sign informed consent

          9. Willing to use effective contraception for at least 100 days post study drug
             administration.

        Exclusion Criteria:

          1. Concurrent treatment with another anti-estrogen

          2. Presence of an active infection requiring systemic therapy

          3. The following conditions contra-indicating fulvestrant administration:

               1. Subjects with bleeding diatheses, thrombocytopenia or current anticoagulant use
                  (excluding aspirin and anti-inflammatories)

               2. Subjects with a known hypersensitivity to fulvestrant or any of its formulation
                  components including castor oil, alcohol, benzyl alcohol, and benzyl benzoate.

               3. Severe hepatic impairment.

          4. Prior surgery on the ipsilateral breast which interrupts communication of the ductal
             systems with the nipple

          5. Prior radiation to the breast

          6. Pregnant or lactating

          7. Impaired cardiac function or history of cardiac problems of NYHA Class 111 and IV

          8. Poor nutritional state as indicated by a BMI below 20.

          9. Presence of serious infection not controlled with systemic therapy

         10. History of allergies to Lidocaine or Novocain

         11. Concurrent participation in an experimental drug study