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

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ClinicalTrials.gov Identifier: NCT04009044
Recruitment Status : Not yet recruiting
First Posted : July 4, 2019
Last Update Posted : July 4, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Northwestern University

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Cancer Survivor Ductal Breast Carcinoma In Situ Invasive Breast Carcinoma Drug: Afimoxifene Procedure: Core Biopsy Other: Questionnaire Administration Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of the Determinants of Transdermal Drug Delivery to the Normal and the Radiated Breast
Estimated Study Start Date : July 25, 2019
Estimated Primary Completion Date : June 9, 2022
Estimated Study Completion Date : June 25, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Treatment (afimoxifene)
Patients apply afimoxifene gel topically QD to both breasts for 4 weeks and then undergo core needle biopsies of both breasts.
Drug: Afimoxifene
Apply topically
Other Names:
  • 4-Hydroxy-Tamoxifen
  • 4-hydroxytamoxifen
  • 4-OHT

Procedure: Core Biopsy
Undergo core needle biopsy
Other Name: core needle biopsy

Other: Questionnaire Administration
Ancillary studies




Primary Outcome Measures :
  1. 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 ]
    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.

  2. Determinants of inter-individual variation in afimoxifene drug concentrations in unradiated breast tissue related to the expression of xenobiotic transporters and enzymes [ Time Frame: Up to 35 days post-treatment ]
    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.

  3. Determinants of inter-individual variation in afimoxifene drug concentrations in unradiated breast tissue related to skin features [ Time Frame: Up to 35 days pot-treatment ]
    Will be measured with confocal reflectance microscopy. 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. A similar analysis will be conducted using the skin characteristics from the confocal reflectance microscopy.


Secondary Outcome Measures :
  1. Effect of breast radiotherapy on drug concentrations resulting from transdermal delivery of afimoxifene (4-OHT) [ Time Frame: Up to 35 days post-treatment ]
    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.

  2. Differences between radiated and non-radiated skin and breast tissue that contribute to differences in permeation [ Time Frame: Up to 35 days post-treatment ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04009044


Locations
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United States, Illinois
Northwestern University Not yet recruiting
Chicago, Illinois, United States, 60611
Contact: Seema A. Khan    312-503-4236    skhan@nm.org   
Principal Investigator: Seema A. Khan         
Sponsors and Collaborators
Northwestern University
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Seema A Khan Northwestern University

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Responsible Party: Northwestern University
ClinicalTrials.gov Identifier: NCT04009044     History of Changes
Other Study ID Numbers: NU 18B05
NCI-2019-03771 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
NU 18B05 ( Other Identifier: Northwestern University )
P30CA060553 ( U.S. NIH Grant/Contract )
First Posted: July 4, 2019    Key Record Dates
Last Update Posted: July 4, 2019
Last Verified: July 2019

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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.: No
Additional relevant MeSH terms:
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Hormones, Hormone Substitutes, and Hormone Antagonists
Carcinoma
Breast Neoplasms
Carcinoma in Situ
Carcinoma, Ductal, Breast
Breast Carcinoma In Situ
Carcinoma, Intraductal, Noninfiltrating
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Carcinoma, Ductal
Adenocarcinoma
Neoplasms, Ductal, Lobular, and Medullary
Afimoxifene
Hydroxytamoxifen
Estrogen Antagonists
Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators