Breast Cancer
Conditions
Keywords
Mastectomy
Brief 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.
Detailed description
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.
Interventions
DRUGzafirlukast
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.
OTHERStandard of Care (no intervention)
Standard of Care (no intervention)
Sponsors
University of California, San Francisco
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 89 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Capsular Thickness | Day 44 to Day 126 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Day 44 to Day 126 | 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. |
| Appearance of Capsular Contracture | After Day 44 to Day 126 | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Zafirlukast 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. | 2 |
| Standard of Care (no Intervention) Standard of Care (no intervention)
Standard of Care (no intervention): Standard of Care (no intervention) | 2 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Zafirlukast | Standard of Care (no Intervention) | Total |
|---|---|---|---|
| Age, Customized 30-39 | 0 Participants | 1 Participants | 1 Participants |
| Age, Customized 40-49 | 1 Participants | 0 Participants | 1 Participants |
| Age, Customized 50-59 | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 2 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 2 Participants | 4 Participants |
| Region of Enrollment United States | 2 participants | 2 participants | 4 participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 2 |
| other Total, other adverse events | 1 / 2 | 2 / 2 |
| serious Total, serious adverse events | 1 / 2 | 0 / 2 |
Outcome results
Primary
Capsular Thickness
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.
Time frame: Day 44 to Day 126
Population: 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.
Secondary
Appearance of Capsular Contracture
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.
Time frame: After Day 44 to Day 126
Population: 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.
Secondary
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
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.
Time frame: Day 44 to Day 126
Population: 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.