ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    A Randomized, Double-blind, Placebo-controlled Study of 4-hydroxytamoxifen Topical Gel in Women with Mammographically Dense Breasts
Previous Study | Return to List | Next Study

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03063619
Recruitment Status : Recruiting
First Posted : February 24, 2017
Last Update Posted : November 24, 2017
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Mammographically Dense Breast Drug: Afimoxifene Other: Laboratory Biomarker Analysis Other: Placebo Other: Questionnaire Administration Phase 2

Detailed Description:

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 152 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: A Randomized, Double-Blind, Placebo-Controlled Study of 4-hydroxytamoxifen Topical Gel in Women With Mammographically Dense Breast
Actual Study Start Date : May 1, 2017
Estimated Primary Completion Date : May 15, 2019
Estimated Study Completion Date : May 15, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Arm A (placebo)
Patients apply placebo gel topically to each breast QD for up to 52 weeks.
Other: Laboratory Biomarker Analysis
Correlative studies

Other: Placebo
Applied topically
Other Names:
  • placebo therapy
  • PLCB
  • sham therapy

Other: Questionnaire Administration
Ancillary studies

Experimental: Arm B (afimoxifene)
Patients apply afimoxifene gel topically to each breast QD for up to 52 weeks.
Drug: Afimoxifene
Applied topically
Other Names:
  • 4-Hydroxy-Tamoxifen
  • 4-Hydroxytamoxifen
  • 4-OHT

Other: Laboratory Biomarker Analysis
Correlative studies

Other: Questionnaire Administration
Ancillary studies




Primary Outcome Measures :
  1. Percent change in mammographic density (MD) (using Cumulus software) in women applying 4mg 4-OHT gel per breast versus placebo [ Time Frame: Baseline up to 12 months ]
    Will be summarized using descriptive statistics, such as mean, standard deviation, median and range for each arm. The difference of the change in percent MD will be compared between two groups using t-test or Wilcoxon rank sum test, when appropriate. Transformation may be performed when necessary to make the measure of MD close to normal distribution before evaluating the change of MD over time between two groups using repeated measures analysis where the intra-patient correlation is taken into consideration, adjusting for other important covariates.


Secondary Outcome Measures :
  1. Automatic software breast density measurement methods to estimate percent change in mammographic breast density [ Time Frame: Baseline up to 12 months ]
    Compared to cumulus method in women applying 4mg of 4-OHT gel per breast vs. placebo.

  2. Breast tissue density [ Time Frame: Up to 12 months ]
    Evaluated by assessing the patterns of collagen matrix. Will be summarized using descriptive statistics, such as mean, standard deviation, median and range for continuous variables and frequency/percentage for discrete variables. The difference of continuous variables between baseline and 52 weeks may be compared between two groups using t-test or Wilcoxon rank sum test, whichever is appropriate. Transformation may be performed when necessary to make continuous variables close to normal distribution before evaluating the change of these continuous variables over time between two groups using r

  3. Hormone-mediated cellular activity [ Time Frame: Up to 12 months ]
    Evaluated by measuring the transcriptional expression levels of ER-alpha and ER-associated genes (SETER/PR index). Will be summarized using descriptive statistics, such as mean, standard deviation, median and range for continuous variables and frequency/percentage for discrete variables. The difference of continuous variables between baseline and 52 weeks may be compared between two groups using t-test or Wilcoxon rank sum test, whichever is appropriate. Transformation may be performed when necessary to make continuous variables close to normal distribution before evaluating the change of thes

  4. Inflammatory response to 4-OHT therapy [ Time Frame: Up to 12 months ]
    Evaluated by measuring COX2 and p16 proteins, and recruitment of CD68 monocytes by immunohistochemistry. Will be summarized using descriptive statistics, such as mean, standard deviation, median and range for continuous variables and frequency/percentage for discrete variables. The difference of continuous variables between baseline and 52 weeks may be compared between two groups using t-test or Wilcoxon rank sum test, whichever is appropriate. Transformation may be performed when necessary to make continuous variables close to normal distribution before evaluating the change of these continuo

  5. Markers of tamoxifen exposure [ Time Frame: Baseline up to 12 months ]
    Serum measurements of 4-OHT and related metabolite levels and factors related to tamoxifen exposures, such as IGF pathway members, CRP, estradiol, and 4-OHT will be measured. Will be summarized using descriptive statistics, such as mean, standard deviation, median and range for continuous variables and frequency/percentage for discrete variables. The difference of continuous variables between baseline and 52 weeks may be compared between two groups using t-test or Wilcoxon rank sum test, whichever is appropriate. Transformation may be performed when necessary to make continuous variables close

  6. Markers of Toxicity assessed using BESS questionnaire [ Time Frame: Baseline up to 12 months ]
    Blood based toxicity markers will be also evaluated (F VIII, vWB factor, SHBG, lipid profile). Will be summarized using descriptive statistics, such as mean, standard deviation, median and range for continuous variables and frequency/percentage for discrete variables. The difference of continuous variables between baseline and 52 weeks may be compared between two groups using t-test or Wilcoxon rank sum test, whichever is appropriate. Transformation may be performed when necessary to make continuous variables close to normal distribution before evaluating the change of these continuous varia

  7. Percentage of women who underwent a change in BIRADS category [ Time Frame: Baseline up to 12 months ]
  8. Percentage of women with >= 10% absolute decrease in quantitative mammographic density percentage [ Time Frame: Baseline up to 12 months ]
    Compared between treated group 4mg per breast 4-OHT gel versus placebo. Will be summarized using descriptive statistics, such as mean, standard deviation, median and range for continuous variables and frequency/percentage for discrete variables. The difference of continuous variables between baseline and 52 weeks may be compared between two groups using t-test or Wilcoxon rank sum test, whichever is appropriate. Transformation may be performed when necessary to make continuous variables close to normal distribution before evaluating the change of these continuous variables over time between t

  9. Pharmacogenomic response to 4-OHT [ Time Frame: Up to 12 months ]
    Evaluated by measuring Ki67 protein by immunohistochemistry and aurora kinase-alpha gene expression. Will be summarized using descriptive statistics, such as mean, standard deviation, median and range for continuous variables and frequency/percentage for discrete variables. The difference of continuous variables between baseline and 52 weeks may be compared between two groups using t-test or Wilcoxon rank sum test, whichever is appropriate. Transformation may be performed when necessary to make continuous variables close to normal distribution before evaluating the change of these continuous v

  10. Reductions in mammographic density after 1 year of 4-OHT vs. placebo gel application [ Time Frame: 24 months ]
    The change in percent MD of the breast from the end of the treatment at 1 year to 1 year after the treatment ends will also be summarized using descriptive statistics, such as mean, standard deviation, median and range for each arm. The difference of this change in percent MD will be compared between two treatment groups using t-test or Wilcoxon rank sum test, when appropriate.

  11. Structure-function activity of TLDUs [ Time Frame: Up to 12 months ]
    Evaluated by counting acinar density. Will be summarized using descriptive statistics, such as mean, standard deviation, median and range for continuous variables and frequency/percentage for discrete variables. The difference of continuous variables between baseline and 52 weeks may be compared between two groups using t-test or Wilcoxon rank sum test, whichever is appropriate. Transformation may be performed when necessary to make continuous variables close to normal distribution before evaluating the change of these continuous variables over time between two groups using repeated measures a



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   40 Years to 55 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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

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): NCT03063619


Contacts
Contact: UT MD Anderson Early Phase Clinical Research Consortium (713) 745-4230 CR_Study_Registration@mdanderson.org

Locations
United States, Florida
Moffitt Cancer Center Not yet recruiting
Tampa, Florida, United States, 33612
Contact: Nagi B. Kumar    813-745-6885    nagi.kumar@moffitt.org   
Principal Investigator: Nagi B. Kumar         
United States, Illinois
Northwestern University Not yet recruiting
Chicago, Illinois, United States, 60611
Contact: Seema A. Khan    312-503-4236    s-khan2@northwestern.edu   
Principal Investigator: Seema A. Khan         
United States, Massachusetts
Dana-Farber Cancer Institute Not yet recruiting
Boston, Massachusetts, United States, 02215
Contact: Judy E. Garber    617-632-5770    Judy_Garber@dfci.harvard.edu   
Principal Investigator: Judy E. Garber         
United States, New York
Columbia University/Herbert Irving Cancer Center Not yet recruiting
New York, New York, United States, 10032
Contact: Katherine D. Crew    212-305-1732    kd59@cumc.columbia.edu   
Principal Investigator: Katherine D. Crew         
United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Powel H. Brown    713-792-4509    phbrown@mdanderson.org   
Principal Investigator: Powel H. Brown         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
Principal Investigator: Banu Arun M.D. Anderson Cancer Center

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03063619     History of Changes
Other Study ID Numbers: NCI-2017-00244
P30CA016672 ( U.S. NIH Grant/Contract )
NCI-2017-00244 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
N01-CN-2012-00034
2017-0328 ( Other Identifier: MD Anderson Cancer Center )
MDA2016-07-02 ( Other Identifier: DCP )
N01CN00034 ( U.S. NIH Grant/Contract )
First Posted: February 24, 2017    Key Record Dates
Last Update Posted: November 24, 2017
Last Verified: November 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Afimoxifene
Antineoplastic Agents
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators