Clinical Trials /

Topical Afimoxifene in Treating Patients With Breast Cancer Who Have Undergone Radiation Therapy on One Breast

NCT04009044

Description:

This phase II trial studies how well topical afimoxifene works in treating patients with breast cancer who have undergone radiation therapy on one breast. Topical afimoxifene is a quick-drying medicated gel that may block the growth of breast cancer cells when applied to the breast skin. The purpose of this research is to determine what effect, if any, differences in skin type between women have on the delivery of topical afimoxifene to the breast tissue, and whether radiation affects the delivery of topical afimoxifene to breast tissue.

Related Conditions:
  • Breast Carcinoma
  • Ductal Carcinoma In Situ
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Topical Afimoxifene in Treating Patients With Breast Cancer Who Have Undergone Radiation Therapy on One Breast
  • Official Title: A Phase II Study of the Determinants of Transdermal Drug Delivery to the Normal and the Radiated Breast

Clinical Trial IDs

  • ORG STUDY ID: NU 18B05
  • SECONDARY ID: NCI-2019-03771
  • SECONDARY ID: NU 18B05
  • SECONDARY ID: P30CA060553
  • NCT ID: NCT04009044

Conditions

  • Cancer Survivor
  • Ductal Breast Carcinoma In Situ
  • Invasive Breast Carcinoma

Interventions

DrugSynonymsArms
Afimoxifene4-Hydroxy-Tamoxifen, 4-hydroxytamoxifen, 4-OHTTreatment (afimoxifene)

Purpose

This phase II trial studies how well topical afimoxifene works in treating patients with breast cancer who have undergone radiation therapy on one breast. Topical afimoxifene is a quick-drying medicated gel that may block the growth of breast cancer cells when applied to the breast skin. The purpose of this research is to determine what effect, if any, differences in skin type between women have on the delivery of topical afimoxifene to the breast tissue, and whether radiation affects the delivery of topical afimoxifene to breast tissue.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To identify the skin features that drive inter-individual variation in dermal drug
      permeation between individuals.

      SECONDARY OBJECTIVES:

      I. To relate breast tissue drug concentration to skin histology, skin vascularity, skin
      transporter proteins, and skin features measured using confocal reflectance microscopy.

      II. To assess the feasibility of transdermal drug delivery to the radiated breast.

      OUTLINE:

      Patients apply afimoxifene gel topically once daily (QD) to both breasts for 4 weeks and then
      undergo core needle biopsies of both breasts.

      Patients receive follow up phone call 21-35 days after biopsy.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (afimoxifene)ExperimentalPatients apply afimoxifene gel topically QD to both breasts for 4 weeks and then undergo core needle biopsies of both breasts.
  • Afimoxifene

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have received prior unilateral breast radiotherapy (RT) for ductal
             breast carcinoma in situ (DCIS) or invasive cancer (>= 12 weeks after the end of RT),
             and have an intact unradiated (non-RT) breast.

               -  Note: The upper limit for interval since RT will be 5 years, since oral endocrine
                  therapy (OET) for DCIS is usually administered during the 5 years that follow the
                  end of RT.

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%).

          -  No history of coagulopathy, or daily use of aspirin/nonsteroidal antiinflammatory
             drugs (NSAIDs).

          -  A prior history of malignancy is allowed, as long as the patient is considered to have
             ?no evaluable disease? and cancer treatment has been completed.

          -  Females of child-bearing potential (FOCBP) and male partners of female participants
             must agree to use TWO effective forms of birth control (abstinence is not an allowed
             method) prior to study entry and for the duration of study participation, and for two
             months following the last dose of study medications. Effective birth control methods
             are: copper IUD (intrauterine device), diaphragm/cervical cap/shield, spermicide,
             contraceptive sponge, condoms. Should a female patient become pregnant or suspect she
             is pregnant while participating in this study, she should inform her treating
             physician immediately.

               -  NOTE: A FOCBP is any woman (regardless of sexual orientation, having undergone a
                  tubal ligation, or remaining celibate by choice) who meets the following
                  criteria:

                    -  Has not undergone a hysterectomy or bilateral oophorectomy

                    -  Has had menses at any time in the preceding 12 consecutive months (and
                       therefore has not been naturally postmenopausal for > 12 months).

          -  FOCBP must have a negative urine pregnancy test within 7 days prior to registration on
             study.

          -  Willingness to avoid exposing breast skin to natural or artificial sunlight (i.e.
             tanning beds) for the duration of the study drug use.

          -  Patients must have the ability to understand and the willingness to sign a written
             informed consent prior to registration on study.

        Exclusion Criteria:

          -  Patients receiving any other investigational agents within 30 days of registration are
             not eligible.

          -  Patients currently using oral selective estrogen receptor modulators (SERMS)
             (tamoxifen, raloxifene, bazedoxifene) are not eligible.

               -  Note: Prior or current endocrine therapy other than SERMs are allowed.

          -  Patients who have a history of allergic reactions attributed to compounds of similar
             chemical or biologic composition afimoxifene (4-OHT) are not eligible.

          -  Patients who have an uncontrolled intercurrent illness including, but not limited to
             any of the following, are not eligible:

               -  Hypertension that is not controlled on medication

               -  Ongoing or active infection requiring systemic treatment

               -  Symptomatic congestive heart failure

               -  Unstable angina pectoris

               -  Cardiac arrhythmia

               -  Psychiatric illness/social situations that would limit compliance with study
                  requirements

               -  Any other illness or condition that the treating investigator feels would
                  interfere with study compliance or would compromise the patient?s safety or study
                  endpoints.

          -  Female patients who are pregnant or nursing are not eligible.

          -  Patients with prior bilateral breast cancer radiotherapy or radiotherapy for lymphoma
             will be excluded.

          -  Patients with skin lesions on the breast that disrupt the stratum corneum (e.g.
             eczema, ulceration) are not eligible.

          -  Patients with a history of endometrial neoplasia are not eligible.

          -  Patients with a history of thromboembolic disease are not eligible.

               -  Note: history of varicose veins and superficial phlebitis is allowed.

          -  Patients who are undergoing active treatment for any malignancy will be excluded.

          -  Male patients are excluded from this study since there are no data regarding skin
             penetration of 4-OHT though male chest wall skin (which is thicker and hairier than
             female chest wall skin).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Determinants of inter-individual variation in afimoxifene drug concentrations in unradiated breast tissue related to skin histology, blood and lymph vessel density
Time Frame:Up to 35 days post-treatment
Safety Issue:
Description:Univariate analyses will relate each characteristic to tissue drug concentration using either correlation analysis for continuous characteristics or a t-test, analysis of variance or rank sum test for categorical characteristics. Multiple linear regression modelling will be used to select those characteristics that provide the strongest independent contribution to the model.

Secondary Outcome Measures

Measure:Effect of breast radiotherapy on drug concentrations resulting from transdermal delivery of afimoxifene (4-OHT)
Time Frame:Up to 35 days post-treatment
Safety Issue:
Description:Tissue drug concentrations will be compared between radiated and non-radiated breasts using a mixed linear model, with breast radiation status as a fixed effect of interest and person as a random effect. Analyses will also be done to compare the skin data (histology, immunohistochemistry [IHC], protein expression, CRS) between radiated and non-radiated breasts. While most characteristics will be continuous, other metrics will be analyzed by using different link functions in similarly constructed generalized linear model.
Measure:Differences between radiated and non-radiated skin and breast tissue that contribute to differences in permeation
Time Frame:Up to 35 days post-treatment
Safety Issue:
Description:Tissue drug concentrations will be compared between radiated and non-radiated breasts using a mixed linear model, with breast radiation status as a fixed effect of interest and person as a random effect. Analyses will also be done to compare the skin data (histology, IHC, protein expression, CRS) between radiated and non-radiated breasts. While most characteristics will be continuous, other metrics will be analyzed by using different link functions in similarly constructed generalized linear model.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Northwestern University

Last Updated

December 16, 2019