Breast Capsular Contracture Following Post-Mastectomy Reconstruction in Women Treated With the Leukotriene Inhibitor Zafirlukast: A Phase II Trial
Breast Capsular Contracture Following Post-Mastectomy Reconstruction in Women Treated With the Leukotriene Inhibitor Zafirlukast: A Phase II Trial
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.
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.

 Patients will be block randomized 1:1 into two cohorts: treatment with zafirlukast and the
 standard of care, or standard of care alone. 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 5 half-lives of the drug. Patients will be seen every 1-2 weeks for expander
 fill, and will be assessed clinically based on the Baker classification system of capsular
 contracture at every appointment. The day of surgery for their expander-implant exchange,
 their Baker classification will also be noted.

 During expander-implant exchange, three representative sections of the expander capsule will
 be collected: medial, lateral and anterior capsule specimens. These specimens will be
 bisected; half will be sent to pathology and half will be collected by the Munster lab. Gross
 and microscopic determination of capsule thickness will be performed by the pathology
 department. The Munster lab will fix and stain the tissues to look for the presence of
 collagen, level of fibrosis and number of myofibroblasts. Fibrosis level and collagen
 presence will be determined by performing immunohistochemistry with a Trichrome stain of the
 tissues, as well as Western blot analysis with Collagen-1. Myofibroblasts will be detected
 using immunohistochemistry with commercially available antibodies.
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.