Mammographically Dense BreastPhase 2NCT03063619
Afimoxifene in Reducing the Risk of Breast Cancer in Women With Mammographically Dense Breast
A Phase 2 study testing Afimoxifene, Laboratory Biomarker Analysis and Questionnaire Administration in people with Mammographically Dense Breast, run by M.D. Anderson Cancer Center at 5 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 to 69 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Mammographically Dense Breast
- What is being tested?
- Afimoxifene, Laboratory Biomarker Analysis and Questionnaire Administration
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 194 participants
- Where
- 5 sitesUnited States
- Study dates
- 30 Jan 2018to 26 Oct 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 69 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Northwestern University
Chicago, Illinois, 60611
M D Anderson Cancer Center
Houston, Texas, 77030
Columbia University/Herbert Irving Cancer Center
New York, New York, 10032
Moffitt Cancer Center
Tampa, Florida, 33612
About this study
Official title: 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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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).
- 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.
- Conditions
- Mammographically Dense Breast
- Being tested
- Afimoxifene, Laboratory Biomarker Analysis, Placebo, Questionnaire Administration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AfimoxifeneDrug
Also called 4-Hydroxy-Tamoxifen, 4-Hydroxytamoxifen, 4-OHT
Applied topically
Laboratory Biomarker AnalysisOther
Correlative studies
PlaceboOther
Also called placebo therapy, PLCB, sham therapy
Applied topically
Questionnaire AdministrationOther
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| Arm A (placebo) | Placebo comparator | Patients apply placebo gel topically to each breast QD for up to 52 weeks. Receives: Other: Laboratory Biomarker Analysis; Other: Placebo; Other: Questionnaire Administration |
| Arm B (afimoxifene) | Experimental | Patients apply afimoxifene gel topically to each breast QD for up to 52 weeks. Receives: Drug: Afimoxifene; Other: Laboratory Biomarker Analysis; Other: Questionnaire Administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mammographic Breast Density Using Cumulus Software
To determine change of mammographic breast density using Cumulus software. Cumulus is a semi-automated computerized measure of dense area that uses reader-based thresholds to define the breast edge and regions of density on a digital or digitized mammogram. Each pixel within the breast area between the skin line and pectoral muscle is segmented into either fat or fibro glandular tissue; this defines the cut-off point.
Measured: Baseline to Month 12
Secondary outcomes (3)
Mammographic Breast Density Using Volpara Software
To determine change of mammographic breast density using Volpara software. Volpara software uses a combination of x-ray physics and machine learning to generate an accurate volumetric measure of breast composition.
Measured: Baseline to Month 12
4-OHT Plasma Levels
To evaluate plasma measurements of 4-OHT levels, Z-4-OH-Tamoxifen.
Measured: Baseline to Month 12
4-OHT Tissue Levels
To evaluate tissue measurements of 4-OHT levels, Z-4-OH-Tamoxifen
Measured: Baseline to Month 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2017
- Study start30 Jan 2018
- Primary completion26 Oct 2021
- Study completion26 Oct 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Mammographically Dense BreastStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 194 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Banu Arun, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03063619
- Sponsor's protocol ID
- 2017-0328
- Other IDs
- NCI-2017-00244, N01-CN-2012-00034, 2017-0328, MDA2016-07-02, N01CN00034
- Status last verified
- Feb 2024
- First submitted
- 22 Feb 2017
- Last updated
- 22 Feb 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo-Controlled Study of 4-hydroxytamoxifen Topical Gel in Women With Mammographically Dense Breast
- ClinicalTrials.gov ID
- NCT03063619
- Acronym / sponsor ID
- 2017-0328
- Conditions
- Mammographically Dense Breast
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 194 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 30 Jan 2018 (actual)
- Primary completion
- 26 Oct 2021 (actual)
- Study completion
- 26 Oct 2021 (actual)
- First posted
- 24 Feb 2017 (actual)
- Results
- Posted 22 Feb 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVES:
- 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:
- 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).
- 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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A (placebo) | Placebo comparator | Other: Laboratory Biomarker Analysis, Other: Placebo, Other: Questionnaire AdministrationPatients apply placebo gel topically to each breast QD for up to 52 weeks. |
| Arm B (afimoxifene) | Experimental | Drug: Afimoxifene, Other: Laboratory Biomarker Analysis, Other: Questionnaire AdministrationPatients apply afimoxifene gel topically to each breast QD for up to 52 weeks. |
Who may qualify
- Ages
- 40 to 69 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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
Key exclusion criteria (10 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AfimoxifeneAlso: 4-Hydroxy-Tamoxifen, 4-Hydroxytamoxifen, 4-OHTApplied topically | Drug | Arm B (afimoxifene) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Arm A (placebo), Arm B (afimoxifene) |
| PlaceboAlso: placebo therapy, PLCB, sham therapyApplied topically | Other | Arm A (placebo) |
| Questionnaire AdministrationAncillary studies | Other | Arm A (placebo), Arm B (afimoxifene) |
Primary outcome
Mammographic Breast Density Using Cumulus Software
Time frame: Baseline to Month 12
To determine change of mammographic breast density using Cumulus software. Cumulus is a semi-automated computerized measure of dense area that uses reader-based thresholds to define the breast edge and regions of density on a digital or digitized mammogram. Each pixel within the breast area between the skin line and pectoral muscle is segmented into either fat or fibro glandular tissue; this defines the cut-off point.
3 secondary outcomes
Mammographic Breast Density Using Volpara Software
Time frame: Baseline to Month 12
4-OHT Plasma Levels
Time frame: Baseline to Month 12
4-OHT Tissue Levels
Time frame: Baseline to Month 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Feb 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- M D Anderson Cancer CenterLink provided by the sponsor.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Banu Arun, MD principal investigator
M.D. Anderson Cancer Center
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Afimoxifene, Laboratory Biomarker Analysis and Questionnaire Administration in people with Mammographically Dense Breast, run by M.D. Anderson Cancer Center at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Feb 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mammographic Breast Density Using Cumulus Software (time frame: Baseline to Month 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Feb 2024.