Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Musculoskeletal Diseases

Nervous System Diseases

Breast Neoplasms

Contracture

Joint Diseases

Muscular Diseases

Respiratory System Agents

All Drugs and Chemicals

Leukotriene Antagonists

Zafirlukast

Anti-Asthmatic Agents

Hormones

Hormone Antagonists

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.

zafirlukast

Standard of Care (no intervention)

Pamela N Munster, MD

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.

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

Compare capsular thickness by gross and microscopic measurement at the time of expander-implant exchange in those treated with zafirlukast (20 mg PO BID) compared with standard of care.

Perform histologic analysis of the capsule specimens to compare overall fibrosis and collagen deposition between the zafirlukast and standard of care groups.

During expander-implant exchange, three representative sections of the expander capsule will be collected: medial, lateral and anterior capsule specimens. 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.

The capsule tissue that is removed at the time of expander-implant exchange will be fixed and histologically assessed for the presence of fibroblasts and myofibroblasts.

University of California, San Francisco

Zafirlukast

zafirlukast: 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)

Standard of Care (no intervention): Standard of Care (no intervention)

Standard of Care (no Intervention)

Total

30-39

40-49

50-59

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Pamela Munster

No participants were analyzed due to a change in post-mastectomy reconstruction standard practice which implements pre-pectoral implants resulting in low accruals to the protocol. The study was closed prior to any measurements taken or histology analyzed as there would have been insufficient data to produce any statistically significant results.

Capsular Thickness

Histologic Analysis: Compare Capsular Thickness by Gross and Microscopic Measurement at the Time of Expander-implant Exchange in Those Treated With Zafirlukast (20 mg PO BID) Compared With Standard of Care

Appearance of Capsular Contracture

Overall Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Breast Capsular Contracture Following Post-Mastectomy Reconstruction in Women Treated With the Leukotriene Inhibitor Zafirlukast: A Phase II Trial	NCT02950480	Breast Cancer	zafirlukast Standard of Car...	18 Years - 89 Years	University of California, San Francisco
Breast Capsular Contracture Following Post-Mastectomy Reconstruction in Women Treated With the Leukotriene Inhibitor Zafirlukast: A Phase II Trial	NCT02950480	Breast Cancer	zafirlukast Standard of Car...	18 Years - 89 Years	University of California, San Francisco

Spots Global Cancer Trial Database for standard of care (no intervention)