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

This study is currently recruiting participants.
See Contacts and Locations
Verified July 2017 by University of California, San Francisco
Sponsor:
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT02950480
First received: September 7, 2016
Last updated: July 25, 2017
Last verified: July 2017
  Purpose
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.

Condition Intervention Phase
Breast Cancer Drug: zafirlukast Other: Standard of Care (no intervention) Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Breast Capsular Contracture Following Post-Mastectomy Reconstruction in Women Treated With the Leukotriene Inhibitor Zafirlukast: A Phase II Trial

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Capsular thickness [ Time Frame: 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 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 [ Time Frame: 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 [ Time Frame: 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.


Estimated Enrollment: 90
Actual Study Start Date: March 13, 2017
Estimated Study Completion Date: January 2020
Estimated Primary Completion Date: January 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Zafirlukast
Zafirlukast
Drug: 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.
Other Name: Accolate
Standard of Care (no intervention)
Standard of Care (no intervention)
Other: Standard of Care (no intervention)
Standard of Care (no intervention)

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.

  Eligibility

Ages Eligible for Study:   18 Years to 89 Years   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients must have histologically confirmed breast malignancy or are undergoing prophylactic mastectomy
  2. Age ≥ 18 years
  3. Scheduled to undergo mastectomy with the immediate placement of tissue expanders
  4. 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: hormonal or barrier method of birth control, prior to study entry and 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.
  5. Ability to understand a written informed consent document, and the willingness to sign it
  6. At least 4 weeks post-completion of chemotherapy
  7. Adequate organ function within 14 days start of study start:

    1. Absolute neutrophil count (ANC) ≥ 1.5 X 109/L
    2. Hemoglobin (Hgb) ≥9g/dL
    3. Platelets (plt) ≥ 100 x 109/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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02950480

Contacts
Contact: Kerry Inokuchi 415-353-9535 Kerry.Inokuchi@ucsf.edu
Contact: Carey Kokkonen 415-514-8418 carey.kokkonen@ucsf.edu

Locations
United States, California
UCSF Helen Diller Family Comprehensive Cancer Center Recruiting
San Francisco, California, United States, 94143-1711
Contact: Pamela N. Munster, MD    877-827-3222    Pmunster@medicine.ucsf.edu   
Sponsors and Collaborators
University of California, San Francisco
Investigators
Principal Investigator: Pamela N Munster, MD University of California, San Francisco
  More Information

Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT02950480     History of Changes
Other Study ID Numbers: 15754
Study First Received: September 7, 2016
Last Updated: July 25, 2017

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

Keywords provided by University of California, San Francisco:
Mastectomy

Additional relevant MeSH terms:
Contracture
Joint Diseases
Musculoskeletal Diseases
Muscular Diseases
Zafirlukast
Leukotriene Antagonists
Anti-Asthmatic Agents
Respiratory System Agents
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 21, 2017