Breast Capsular Contracture Following Post-Mastectomy Reconstruction in Women Treated With the Leukotriene Inhibitor Zafirlukast: A Phase II Trial
Primary Purpose
Breast Cancer
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
zafirlukast
Standard of Care (no intervention)
Sponsored by
About this trial
This is an interventional treatment trial for Breast Cancer focused on measuring Mastectomy
Eligibility Criteria
Inclusion Criteria:
- 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
- Age ≥ 18 years
- 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.
- Ability to understand a written informed consent document, and the willingness to sign it
- At least 4 weeks post-completion of chemotherapy
Adequate organ function within 14 days start of study start:
- Absolute neutrophil count (ANC) ≥ 1.5 X 10^9/L
- Hemoglobin (Hgb) ≥9g/dL
- Platelets (plt) ≥ 100 x 10^9/L
- Potassium within normal range, or correctable with supplements;
- AST and ALT ≤2.5 x Upper Limit Normal (ULN) or ≤5.0 x ULN if liver tumor is present;
- Serum total bilirubin ≤ 1.5 x ULN
- Serum creatinine ≤ 1.5 x ULN, or 24-hr clearance ≥ 60ml/min
Exclusion Criteria:
- Any significant medical condition, laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study
- Currently on a leukotriene inhibitor or used within the past 6 months
- Prior chest wall radiation
- Pregnant or breastfeeding
Hepatic impairment as defined by:
• AST(SGOT) > 2.5X institutional ULN and ALT(SGPT) > 2.5X institutional ULN
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
Sites / Locations
- UCSF Helen Diller Family Comprehensive Cancer Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Other
Arm Label
Zafirlukast
Standard of Care (no intervention)
Arm Description
Zafirlukast
Standard of Care (no intervention)
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
Full Information
NCT ID
NCT02950480
First Posted
September 7, 2016
Last Updated
September 11, 2019
Sponsor
University of California, San Francisco
1. Study Identification
Unique Protocol Identification Number
NCT02950480
Brief Title
Breast Capsular Contracture Following Post-Mastectomy Reconstruction in Women Treated With the Leukotriene Inhibitor Zafirlukast: A Phase II Trial
Official Title
Breast Capsular Contracture Following Post-Mastectomy Reconstruction in Women Treated With the Leukotriene Inhibitor Zafirlukast: A Phase II Trial
Study Type
Interventional
2. Study Status
Record Verification Date
September 2019
Overall Recruitment Status
Terminated
Why Stopped
Low accrual.
Study Start Date
March 13, 2017 (Actual)
Primary Completion Date
December 20, 2018 (Actual)
Study Completion Date
December 20, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, San Francisco
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer
Keywords
Mastectomy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
4 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Zafirlukast
Arm Type
Experimental
Arm Description
Zafirlukast
Arm Title
Standard of Care (no intervention)
Arm Type
Other
Arm Description
Standard of Care (no intervention)
Intervention Type
Drug
Intervention Name(s)
zafirlukast
Other Intervention Name(s)
Accolate
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.
Intervention Type
Other
Intervention Name(s)
Standard of Care (no intervention)
Intervention Description
Standard of Care (no intervention)
Primary Outcome Measure Information:
Title
Capsular Thickness
Description
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
Secondary Outcome Measure Information:
Title
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
Description
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
Title
Appearance of Capsular Contracture
Description
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
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
89 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Age ≥ 18 years
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.
Ability to understand a written informed consent document, and the willingness to sign it
At least 4 weeks post-completion of chemotherapy
Adequate organ function within 14 days start of study start:
Absolute neutrophil count (ANC) ≥ 1.5 X 10^9/L
Hemoglobin (Hgb) ≥9g/dL
Platelets (plt) ≥ 100 x 10^9/L
Potassium within normal range, or correctable with supplements;
AST and ALT ≤2.5 x Upper Limit Normal (ULN) or ≤5.0 x ULN if liver tumor is present;
Serum total bilirubin ≤ 1.5 x ULN
Serum creatinine ≤ 1.5 x ULN, or 24-hr clearance ≥ 60ml/min
Exclusion Criteria:
Any significant medical condition, laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study
Currently on a leukotriene inhibitor or used within the past 6 months
Prior chest wall radiation
Pregnant or breastfeeding
Hepatic impairment as defined by:
• AST(SGOT) > 2.5X institutional ULN and ALT(SGPT) > 2.5X institutional ULN
Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pamela N Munster, MD
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
Facility Information:
Facility Name
UCSF Helen Diller Family Comprehensive Cancer Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94143-1711
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Breast Capsular Contracture Following Post-Mastectomy Reconstruction in Women Treated With the Leukotriene Inhibitor Zafirlukast: A Phase II Trial
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