Trial Outcomes & Findings for Breast Capsular Contracture Following Post-Mastectomy Reconstruction in Women Treated With the Leukotriene Inhibitor Zafirlukast: A Phase II Trial (NCT NCT02950480)

Last Updated: 2019-10-01

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

4 participants

Primary outcome timeframe

Day 44 to Day 126

Results posted on

2019-10-01

Participant Flow

Participant milestones

Participant milestones
Measure	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.	Standard of Care (no Intervention) Standard of Care (no intervention) Standard of Care (no intervention): Standard of Care (no intervention)
Overall Study STARTED	2	2
Overall Study COMPLETED	1	2
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	Standard of Care (no Intervention) Standard of Care (no intervention) Standard of Care (no intervention): Standard of Care (no intervention)
Overall Study Withdrawal by Subject	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Zafirlukast n=2 Participants 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) n=2 Participants Standard of Care (no intervention) Standard of Care (no intervention): Standard of Care (no intervention)	Total n=4 Participants Total of all reporting groups
Age, Customized 30-39	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants
Age, Customized 40-49	1 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants
Age, Customized 50-59	1 Participants n=99 Participants	1 Participants n=107 Participants	2 Participants n=206 Participants
Sex: Female, Male Female	2 Participants n=99 Participants	2 Participants n=107 Participants	4 Participants n=206 Participants
Sex: Female, Male Male	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants n=99 Participants	2 Participants n=107 Participants	4 Participants n=206 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) White	2 Participants n=99 Participants	2 Participants n=107 Participants	4 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Region of Enrollment United States	2 participants n=99 Participants	2 participants n=107 Participants	4 participants n=206 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

Adverse Events

Zafirlukast

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Standard of Care (no Intervention)

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Zafirlukast n=2 participants at risk 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) n=2 participants at risk Standard of Care (no intervention) Standard of Care (no intervention): Standard of Care (no intervention)
Infections and infestations Breast Infection	50.0% 1/2 • Number of events 1 • Adverse Events will be assessed at time of mastectomy and tissue expander placement (week 0), week 2, week 5, week 11, and week 17 until 30 days after treatment termination. Serious adverse events were collected for 30 days after the end of treatment, or until death, whichever occurs first. Patients removed from treatment for unacceptable treatment related adverse event(s) were followed until resolution or stabilization of all treatment related adverse events to Grade 1 or baseline.	0.00% 0/2 • Adverse Events will be assessed at time of mastectomy and tissue expander placement (week 0), week 2, week 5, week 11, and week 17 until 30 days after treatment termination. Serious adverse events were collected for 30 days after the end of treatment, or until death, whichever occurs first. Patients removed from treatment for unacceptable treatment related adverse event(s) were followed until resolution or stabilization of all treatment related adverse events to Grade 1 or baseline.

Other adverse events

Other adverse events
Measure	Zafirlukast n=2 participants at risk 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) n=2 participants at risk Standard of Care (no intervention) Standard of Care (no intervention): Standard of Care (no intervention)
General disorders Fatigue	50.0% 1/2 • Number of events 1 • Adverse Events will be assessed at time of mastectomy and tissue expander placement (week 0), week 2, week 5, week 11, and week 17 until 30 days after treatment termination. Serious adverse events were collected for 30 days after the end of treatment, or until death, whichever occurs first. Patients removed from treatment for unacceptable treatment related adverse event(s) were followed until resolution or stabilization of all treatment related adverse events to Grade 1 or baseline.	50.0% 1/2 • Number of events 1 • Adverse Events will be assessed at time of mastectomy and tissue expander placement (week 0), week 2, week 5, week 11, and week 17 until 30 days after treatment termination. Serious adverse events were collected for 30 days after the end of treatment, or until death, whichever occurs first. Patients removed from treatment for unacceptable treatment related adverse event(s) were followed until resolution or stabilization of all treatment related adverse events to Grade 1 or baseline.
General disorders Pain	0.00% 0/2 • Adverse Events will be assessed at time of mastectomy and tissue expander placement (week 0), week 2, week 5, week 11, and week 17 until 30 days after treatment termination. Serious adverse events were collected for 30 days after the end of treatment, or until death, whichever occurs first. Patients removed from treatment for unacceptable treatment related adverse event(s) were followed until resolution or stabilization of all treatment related adverse events to Grade 1 or baseline.	100.0% 2/2 • Number of events 2 • Adverse Events will be assessed at time of mastectomy and tissue expander placement (week 0), week 2, week 5, week 11, and week 17 until 30 days after treatment termination. Serious adverse events were collected for 30 days after the end of treatment, or until death, whichever occurs first. Patients removed from treatment for unacceptable treatment related adverse event(s) were followed until resolution or stabilization of all treatment related adverse events to Grade 1 or baseline.
General disorders Edema limbs	0.00% 0/2 • Adverse Events will be assessed at time of mastectomy and tissue expander placement (week 0), week 2, week 5, week 11, and week 17 until 30 days after treatment termination. Serious adverse events were collected for 30 days after the end of treatment, or until death, whichever occurs first. Patients removed from treatment for unacceptable treatment related adverse event(s) were followed until resolution or stabilization of all treatment related adverse events to Grade 1 or baseline.	50.0% 1/2 • Number of events 1 • Adverse Events will be assessed at time of mastectomy and tissue expander placement (week 0), week 2, week 5, week 11, and week 17 until 30 days after treatment termination. Serious adverse events were collected for 30 days after the end of treatment, or until death, whichever occurs first. Patients removed from treatment for unacceptable treatment related adverse event(s) were followed until resolution or stabilization of all treatment related adverse events to Grade 1 or baseline.
General disorders Edema trunk	0.00% 0/2 • Adverse Events will be assessed at time of mastectomy and tissue expander placement (week 0), week 2, week 5, week 11, and week 17 until 30 days after treatment termination. Serious adverse events were collected for 30 days after the end of treatment, or until death, whichever occurs first. Patients removed from treatment for unacceptable treatment related adverse event(s) were followed until resolution or stabilization of all treatment related adverse events to Grade 1 or baseline.	50.0% 1/2 • Number of events 1 • Adverse Events will be assessed at time of mastectomy and tissue expander placement (week 0), week 2, week 5, week 11, and week 17 until 30 days after treatment termination. Serious adverse events were collected for 30 days after the end of treatment, or until death, whichever occurs first. Patients removed from treatment for unacceptable treatment related adverse event(s) were followed until resolution or stabilization of all treatment related adverse events to Grade 1 or baseline.
General disorders Localized edema	0.00% 0/2 • Adverse Events will be assessed at time of mastectomy and tissue expander placement (week 0), week 2, week 5, week 11, and week 17 until 30 days after treatment termination. Serious adverse events were collected for 30 days after the end of treatment, or until death, whichever occurs first. Patients removed from treatment for unacceptable treatment related adverse event(s) were followed until resolution or stabilization of all treatment related adverse events to Grade 1 or baseline.	50.0% 1/2 • Number of events 2 • Adverse Events will be assessed at time of mastectomy and tissue expander placement (week 0), week 2, week 5, week 11, and week 17 until 30 days after treatment termination. Serious adverse events were collected for 30 days after the end of treatment, or until death, whichever occurs first. Patients removed from treatment for unacceptable treatment related adverse event(s) were followed until resolution or stabilization of all treatment related adverse events to Grade 1 or baseline.
Gastrointestinal disorders Abdominal pain	0.00% 0/2 • Adverse Events will be assessed at time of mastectomy and tissue expander placement (week 0), week 2, week 5, week 11, and week 17 until 30 days after treatment termination. Serious adverse events were collected for 30 days after the end of treatment, or until death, whichever occurs first. Patients removed from treatment for unacceptable treatment related adverse event(s) were followed until resolution or stabilization of all treatment related adverse events to Grade 1 or baseline.	50.0% 1/2 • Number of events 1 • Adverse Events will be assessed at time of mastectomy and tissue expander placement (week 0), week 2, week 5, week 11, and week 17 until 30 days after treatment termination. Serious adverse events were collected for 30 days after the end of treatment, or until death, whichever occurs first. Patients removed from treatment for unacceptable treatment related adverse event(s) were followed until resolution or stabilization of all treatment related adverse events to Grade 1 or baseline.
Gastrointestinal disorders Nausea	50.0% 1/2 • Number of events 1 • Adverse Events will be assessed at time of mastectomy and tissue expander placement (week 0), week 2, week 5, week 11, and week 17 until 30 days after treatment termination. Serious adverse events were collected for 30 days after the end of treatment, or until death, whichever occurs first. Patients removed from treatment for unacceptable treatment related adverse event(s) were followed until resolution or stabilization of all treatment related adverse events to Grade 1 or baseline.	0.00% 0/2 • Adverse Events will be assessed at time of mastectomy and tissue expander placement (week 0), week 2, week 5, week 11, and week 17 until 30 days after treatment termination. Serious adverse events were collected for 30 days after the end of treatment, or until death, whichever occurs first. Patients removed from treatment for unacceptable treatment related adverse event(s) were followed until resolution or stabilization of all treatment related adverse events to Grade 1 or baseline.
Nervous system disorders Nervous system disorders - Other, specify	0.00% 0/2 • Adverse Events will be assessed at time of mastectomy and tissue expander placement (week 0), week 2, week 5, week 11, and week 17 until 30 days after treatment termination. Serious adverse events were collected for 30 days after the end of treatment, or until death, whichever occurs first. Patients removed from treatment for unacceptable treatment related adverse event(s) were followed until resolution or stabilization of all treatment related adverse events to Grade 1 or baseline.	50.0% 1/2 • Number of events 1 • Adverse Events will be assessed at time of mastectomy and tissue expander placement (week 0), week 2, week 5, week 11, and week 17 until 30 days after treatment termination. Serious adverse events were collected for 30 days after the end of treatment, or until death, whichever occurs first. Patients removed from treatment for unacceptable treatment related adverse event(s) were followed until resolution or stabilization of all treatment related adverse events to Grade 1 or baseline.
Nervous system disorders Peripheral sensory neuropathy	50.0% 1/2 • Number of events 1 • Adverse Events will be assessed at time of mastectomy and tissue expander placement (week 0), week 2, week 5, week 11, and week 17 until 30 days after treatment termination. Serious adverse events were collected for 30 days after the end of treatment, or until death, whichever occurs first. Patients removed from treatment for unacceptable treatment related adverse event(s) were followed until resolution or stabilization of all treatment related adverse events to Grade 1 or baseline.	0.00% 0/2 • Adverse Events will be assessed at time of mastectomy and tissue expander placement (week 0), week 2, week 5, week 11, and week 17 until 30 days after treatment termination. Serious adverse events were collected for 30 days after the end of treatment, or until death, whichever occurs first. Patients removed from treatment for unacceptable treatment related adverse event(s) were followed until resolution or stabilization of all treatment related adverse events to Grade 1 or baseline.
Injury, poisoning and procedural complications Wound dehiscence	50.0% 1/2 • Number of events 1 • Adverse Events will be assessed at time of mastectomy and tissue expander placement (week 0), week 2, week 5, week 11, and week 17 until 30 days after treatment termination. Serious adverse events were collected for 30 days after the end of treatment, or until death, whichever occurs first. Patients removed from treatment for unacceptable treatment related adverse event(s) were followed until resolution or stabilization of all treatment related adverse events to Grade 1 or baseline.	0.00% 0/2 • Adverse Events will be assessed at time of mastectomy and tissue expander placement (week 0), week 2, week 5, week 11, and week 17 until 30 days after treatment termination. Serious adverse events were collected for 30 days after the end of treatment, or until death, whichever occurs first. Patients removed from treatment for unacceptable treatment related adverse event(s) were followed until resolution or stabilization of all treatment related adverse events to Grade 1 or baseline.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	0.00% 0/2 • Adverse Events will be assessed at time of mastectomy and tissue expander placement (week 0), week 2, week 5, week 11, and week 17 until 30 days after treatment termination. Serious adverse events were collected for 30 days after the end of treatment, or until death, whichever occurs first. Patients removed from treatment for unacceptable treatment related adverse event(s) were followed until resolution or stabilization of all treatment related adverse events to Grade 1 or baseline.	50.0% 1/2 • Number of events 1 • Adverse Events will be assessed at time of mastectomy and tissue expander placement (week 0), week 2, week 5, week 11, and week 17 until 30 days after treatment termination. Serious adverse events were collected for 30 days after the end of treatment, or until death, whichever occurs first. Patients removed from treatment for unacceptable treatment related adverse event(s) were followed until resolution or stabilization of all treatment related adverse events to Grade 1 or baseline.
Musculoskeletal and connective tissue disorders Joint range of motion decreased	0.00% 0/2 • Adverse Events will be assessed at time of mastectomy and tissue expander placement (week 0), week 2, week 5, week 11, and week 17 until 30 days after treatment termination. Serious adverse events were collected for 30 days after the end of treatment, or until death, whichever occurs first. Patients removed from treatment for unacceptable treatment related adverse event(s) were followed until resolution or stabilization of all treatment related adverse events to Grade 1 or baseline.	50.0% 1/2 • Number of events 1 • Adverse Events will be assessed at time of mastectomy and tissue expander placement (week 0), week 2, week 5, week 11, and week 17 until 30 days after treatment termination. Serious adverse events were collected for 30 days after the end of treatment, or until death, whichever occurs first. Patients removed from treatment for unacceptable treatment related adverse event(s) were followed until resolution or stabilization of all treatment related adverse events to Grade 1 or baseline.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify	0.00% 0/2 • Adverse Events will be assessed at time of mastectomy and tissue expander placement (week 0), week 2, week 5, week 11, and week 17 until 30 days after treatment termination. Serious adverse events were collected for 30 days after the end of treatment, or until death, whichever occurs first. Patients removed from treatment for unacceptable treatment related adverse event(s) were followed until resolution or stabilization of all treatment related adverse events to Grade 1 or baseline.	50.0% 1/2 • Number of events 1 • Adverse Events will be assessed at time of mastectomy and tissue expander placement (week 0), week 2, week 5, week 11, and week 17 until 30 days after treatment termination. Serious adverse events were collected for 30 days after the end of treatment, or until death, whichever occurs first. Patients removed from treatment for unacceptable treatment related adverse event(s) were followed until resolution or stabilization of all treatment related adverse events to Grade 1 or baseline.
Vascular disorders Hot flashes	0.00% 0/2 • Adverse Events will be assessed at time of mastectomy and tissue expander placement (week 0), week 2, week 5, week 11, and week 17 until 30 days after treatment termination. Serious adverse events were collected for 30 days after the end of treatment, or until death, whichever occurs first. Patients removed from treatment for unacceptable treatment related adverse event(s) were followed until resolution or stabilization of all treatment related adverse events to Grade 1 or baseline.	50.0% 1/2 • Number of events 1 • Adverse Events will be assessed at time of mastectomy and tissue expander placement (week 0), week 2, week 5, week 11, and week 17 until 30 days after treatment termination. Serious adverse events were collected for 30 days after the end of treatment, or until death, whichever occurs first. Patients removed from treatment for unacceptable treatment related adverse event(s) were followed until resolution or stabilization of all treatment related adverse events to Grade 1 or baseline.

Additional Information

Dr. Pamela Munster

University of California, San Francisco

Phone: (415) 885-7810

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place