Afimoxifene in Reducing the Risk of Breast Cancer in Women With Mammographically Dense Breast
Ключови думи
Резюме
Описание
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.
Дати
Последна проверка: | 12/31/2019 |
Първо изпратено: | 02/21/2017 |
Очаквано записване подадено: | 02/21/2017 |
Първо публикувано: | 02/23/2017 |
Изпратена последна актуализация: | 01/30/2020 |
Последна актуализация публикувана: | 02/04/2020 |
Действителна начална дата на проучването: | 04/30/2017 |
Приблизителна дата на първично завършване: | 09/17/2020 |
Очаквана дата на завършване на проучването: | 09/17/2020 |
Състояние или заболяване
Интервенция / лечение
Drug: Arm B (afimoxifene)
Other: Laboratory Biomarker Analysis
Other: Arm A (placebo)
Other: Questionnaire Administration
Фаза
Групи за ръце
Arm | Интервенция / лечение |
---|---|
Placebo Comparator: Arm A (placebo) Patients apply placebo gel topically to each breast QD for up to 52 weeks. | Other: Arm A (placebo) Applied topically |
Experimental: Arm B (afimoxifene) Patients apply afimoxifene gel topically to each breast QD for up to 52 weeks. | Drug: Arm B (afimoxifene) Applied topically |
Критерии за допустимост
Възрасти, отговарящи на условията за проучване | 40 Years Да се 40 Years |
Полове, допустими за проучване | Female |
Приема здрави доброволци | Да |
Критерии | Inclusion Criteria: - Women age 40-69 years, or 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 |
Резултат
Първични изходни мерки
1. Percent change in mammographic density (MD) (using Cumulus software) in women applying 4mg 4-OHT gel per breast versus placebo [Baseline up to 12 months]
Вторични изходни мерки
1. Automatic software breast density measurement methods to estimate percent change in mammographic breast density [Baseline up to 12 months]
2. Breast tissue density [Up to 12 months]
3. Hormone-mediated cellular activity [Up to 12 months]
4. Inflammatory response to 4-OHT therapy [Up to 12 months]
5. Markers of tamoxifen exposure [Baseline up to 12 months]
6. Markers of Toxicity assessed using BESS questionnaire [Baseline up to 12 months]
7. Percentage of women who underwent a change in BIRADS category [Baseline up to 12 months]
8. Percentage of women with >= 10% absolute decrease in quantitative mammographic density percentage [Baseline up to 12 months]
9. Pharmacogenomic response to 4-OHT [Up to 12 months]
10. Reductions in mammographic density after 1 year of 4-OHT vs. placebo gel application [24 months]
11. Structure-function activity of TLDUs [Up to 12 months]