Afimoxifene in Reducing the Risk of Breast Cancer in Women With Mammographically Dense Breast



Status:Recruiting
Healthy:No
Age Range:40 - 55
Updated:12/1/2018
Start Date:May 1, 2017
End Date:May 15, 2019
Contact:UT MD Anderson Early Phase Clinical Research Consortium
Email:CR_Study_Registration@mdanderson.org
Phone:(713) 745-4230

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A Randomized, Double-Blind, Placebo-Controlled Study of 4-hydroxytamoxifen Topical Gel in Women With Mammographically Dense Breast

This randomized phase II trial studies how well afimoxifene works in reducing the risk of
breast cancer in women with mammographically dense breast. Estrogen can cause the growth of
breast cancer cells. Hormone therapy using afimoxifene may fight breast cancer by blocking
the use of estrogen by the tumor cells.

PRIMARY OBJECTIVES:

I. To estimate and compare the percent change in mammographic breast density (using Cumulus
software) from baseline to month 12 in women applying 4mg afimoxifene (4-hydroxytamoxifen
[4-OHT]) gel per breast versus placebo.

SECONDARY OBJECTIVES:

I. To compare the Cumulus versus (vs.) Volpara breast density measurement methods to estimate
percent change in mammographic breast density from baseline to month 12 in women applying 4mg
of 4-OHT gel per breast vs. placebo.

II. To compare the percentage of women who underwent a change in Breast Imaging Reporting and
Data System (BIRADS) category, comparing pre-and post- treatment measurements, for recipients
of active agent versus placebo.

III. To estimate percentage of women with >= 10% absolute decrease in quantitative
mammographic density percentage between baseline and 12 months, comparing between treated
group 4mg per breast 4-OHT gel to placebo.

IV. To describe symptoms assessed by breast cancer prevention trial (BCPT) eight symptom
scale (BESS) questionnaire and laboratory toxicity assessment (factor VIII [F VIII], Von
Willebrand [vWB] factor, sex hormone-binding globulin [SHBG], lipid profile).

V. To evaluate serum measurements of 4-OHT and related metabolite levels and factors related
to tamoxifen exposures, such as insulin-like growth factor (IGF) pathway members, C-reactive
protein (CRP), estradiol.

VI. To evaluate tissue biomarkers (among women undergoing optional pre- and post-treatment
biopsies): terminal duct lobular unit (TDLU) involution; collagen structural changes;
SETER/PR index: estrogen related transcription, Ki-67, COX-2, p16, CD68.

VII. To examine whether any reductions in mammographic density seen after 1 year of 4-OHT vs.
placebo gel application persist at 24 months, one year after gel application has stopped.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients apply placebo gel topically to each breast once daily (QD) for up to 52
weeks.

ARM B: Patients apply afimoxifene gel topically to each breast QD for up to 52 weeks.

After completion of study treatment, patients are followed up at 24 months.

Inclusion Criteria:

- Less than 40 years if 5-year breast cancer Gail risk is >= 1.66%

- Mammographically dense breast (heterogeneously dense [C] or extremely dense [D], based
on American College of Radiology [ACR] BIRADS fifth edition classification or
heterogeneously dense [3] or extremely dense [4], based on ACR BIRADS fourth edition
classification) in either breast

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

- White blood cells >= 3,000/microliter

- Absolute neutrophil count >= 1,500/microliter

- Platelets >= 100,000/microliter

- Total bilirubin within normal institutional limits

- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 1.5 × institutional upper limit of normal (ULN)

- Creatinine within normal institutional limits

- Participant must have a gynecology examination within the last 3 years, with no
atypical hyperplasia and no cancer

- Premenopausal women taking non hormonal intra-uterine device (IUD) birth control
method will be eligible, if they have been on the same IUD for at least 3 months prior
to enrollment and plan to continue using the same method throughout the study

- Women of child-bearing potential must agree to use a reliable nonhormonal
contraceptive method during the study and for 2 months after completing study
medications; reliable nonhormonal methods of contraception include barrier
contraception and an intra-uterine device (IUD); Note: women who had tubal ligation or
had a partner who had undergone a vasectomy (and are monogamous) are eligible for the
study and are not required to use barrier contraception

- If the participant is of childbearing potential, she must have a documented negative
urine pregnancy test within 7 days prior to randomization

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

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to 4-OHT gel

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, thromboembolic disease, or psychiatric illness/social situations that
would limit compliance with study requirements

- Pregnant, or had given birth, or nursed at any time during the last 12 months

- Women with a previous history of invasive breast cancer or bilateral ductal carcinoma
in situ (DCIS) or current untreated DCIS; women with a history of cancer within the
last 3 years, except for non-melanoma skin cancer; women with unilateral DCIS (with or
without radiation therapy) are eligible as long as they have an unaffected breast

- Prior bilateral breast surgery (mastectomy, segmental mastectomy, or breast
augmentation surgery including breast implants or breast reductions)

- Women with "mosaic mammographic screening views", i.e., whose larger breast size
precludes being imaged within a single mammographic screening view

- Women with active liver disease, abnormal uterine bleeding, or prior diagnosis of
endometrial hyperplasia

- Prior use of selective estrogen receptor modulators (SERMS) and aromatase inhibitors
(AIs) for prevention or therapy

- Skin lesions on the breast that disrupt the stratum corneum (e.g., eczema, ulceration)

- Treatment with any investigational drug or investigational biologic within 30 days of
initiating study treatment or during the study
We found this trial at
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Tampa, Florida 33612
Principal Investigator: Nagi B. Kumar
Phone: 813-745-6885
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Boston, Massachusetts 2215
617-632-3000
Principal Investigator: Judy E. Garber
Phone: 617-632-5770
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Chicago, Illinois 60611
Principal Investigator: Seema A. Khan
Phone: 312-503-4236
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Principal Investigator: Powel H. Brown
Phone: 713-792-4509
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New York, New York 10032
Principal Investigator: Katherine D. Crew
Phone: 212-305-1732
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