Breast Capsular Contracture Following Post-Mastectomy Reconstruction in Women Treated With the Leukotriene Inhibitor Zafirlukast: A Phase II Trial
Condition: Breast Cancer
MeSH terms: Contracture
Intervention: zafirlukast; Standard of Care (no intervention)
Intervention description: Patients will begin treatment with zafirlukast on post-operative day one following placement of tissue expander(s) once determined safe from a surgical recovery standpoint. They will be continued on the standard dosing (20mg PO twice per day) of zafirlukast through expander fill (6-12 weeks, up to 18 weeks for women receiving radiation). Treatment will be stopped 48 hours prior to expander-implant exchange, which is equivalent to five half-lives of the drug. Patients will be seen every 1 to 2 weeks for expander fill, and will be assessed clinically based on the Baker classification system of capsular contracture every two weeks.; Standard of Care (no intervention)
Intervention MeSH terms: Zafirlukast
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 4.0
Sex: Female
Minimum age: 18 Years
Maximum age: 89 Years
Healthy volunteers: No
Keywords: Mastectomy

Summary:

      A 2 arm, 90 patient (45 per cohort) trial in patients with breast cancer who will be
      undergoing mastectomy with immediate tissue-expander reconstruction to determine whether
      treatment with zafirlukast (20mg PO BID) can reduce or prevent the development of capsular
      contracture.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients who are scheduled to undergo therapeutic or prophylactic mastectomy with
             immediate placement of tissue expanders and have a strong family history or hereditary
             cancer

          2. Age ≥ 18 years

          3. Zafirlukast is pregnancy category B. There are no adequate and well-controlled trials
             in pregnant women. Therefore, the effects of zafirlukast on the developing human fetus
             are unknown. For this reason, women of child-bearing potential must agree to use
             adequate contraception: 2 methods of birth control, prior to study entry ad for the
             duration of study participation. Should a woman become pregnant or suspect she is
             pregnant while she is participating in this study, she should inform her treating
             physician immediately.

          4. Ability to understand a written informed consent document, and the willingness to sign
             it

          5. At least 4 weeks post-completion of chemotherapy

          6. Adequate organ function within 14 days start of study start:

               1. Absolute neutrophil count (ANC) ≥ 1.5 X 10^9/L

               2. Hemoglobin (Hgb) ≥9g/dL

               3. Platelets (plt) ≥ 100 x 10^9/L

               4. Potassium within normal range, or correctable with supplements;

               5. AST and ALT ≤2.5 x Upper Limit Normal (ULN) or ≤5.0 x ULN if liver tumor is
                  present;

               6. Serum total bilirubin ≤ 1.5 x ULN

               7. Serum creatinine ≤ 1.5 x ULN, or 24-hr clearance ≥ 60ml/min

        Exclusion Criteria:

          1. Any significant medical condition, laboratory abnormalities, which places the subject
             at unacceptable risk if he/she were to participate in the study

          2. Currently on a leukotriene inhibitor or used within the past 6 months

          3. Prior chest wall radiation

          4. Pregnant or breastfeeding

          5. Hepatic impairment as defined by:

             • AST(SGOT) > 2.5X institutional ULN and ALT(SGPT) > 2.5X institutional ULN

          6. Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial.