Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Carcinoma

Breast Neoplasms

Carcinoma in Situ

Breast Carcinoma In Situ

Carcinoma, Intraductal, Noninfiltrating

Carcinoma, Ductal, Breast

Carcinoma, Ductal

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Breast Diseases

Skin Diseases

Adenocarcinoma

Bone Density Conservation Agents

Antineoplastic Agents

All Drugs and Chemicals

Tamoxifen

Afimoxifene

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Estrogen Receptor Modulators

Selective Estrogen Receptor Modulators

Patients apply afimoxifene gel topically QD to both breasts for 3 to 5 weeks and then undergo core needle biopsies of both breasts.

Core Biopsy

Questionnaire Administration

Study Coordinator

Seema A. Khan, M.D.

Kent Hoskins, MD, BA

Seema A Khan, M.D.

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.

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.

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

A Phase II Study of the Determinants of Transdermal Drug Delivery to the Normal and the Radiated Breast

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.

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.

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.

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.

National Cancer Institute (NCI)

Northwestern University

Patients apply placebo gel topically to each breast QD for up to 52 weeks.

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

Laboratory Biomarker Analysis

Placebo

Banu Arun, MD

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.

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

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

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.

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.

To evaluate plasma measurements of 4-OHT levels, Z-4-OH-Tamoxifen.

To evaluate tissue measurements of 4-OHT levels, Z-4-OH-Tamoxifen

M.D. Anderson Cancer Center

Participants apply 4-OHT Gel topically to each breast QD for up to 52 weeks.

4-OHT Gel: Applied topically

4-OHT Gel

Participants apply Placebo gel topically to each breast QD for up to 52 weeks.

Placebo: Applied topically

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Banu Arun

Craniocaudal View (CC view)

Mediolateral Oblique View (MLO view)

Mammographic breast density data are available in a total of 133 participants, two without baseline data, six without month-12 data and two with 12-month mammograms beyond 18 months therefore are not considered evaluable for Month 12 evaluation. Therefore, a total of 123 participants are evaluable for the primary endpoint, 61 in 4-OHT and 62 in Placebo.

Mammographic Breast Density Using Cumulus Software

A total of 59 participants have been evaluated for breast density at either baseline or month 12 or both by Volpara data, however 23 in 4-OHT and 24 in Placebo by CC view, and 25 in 4-OHT and 24 in Placebo by MLO view are evaluable for percent change in mammographic breast density.

Mammographic Breast Density Using Volpara Software

Below Qualification Limit (BQL) at 12 months

Greater than BQL at 12 months

A total of 59 and 57 participants in 4-OHT and Placebo arms, respectively, have Month 12 measures on 4-OHT in plasma. All baseline measures are Below Qualification Limit (BQL).

4-OHT Plasma Levels

Below Qualification Limit (BQL)

Greater than BQL

A total of 12 and 18 participants in 4-OHT and Placebo arms, respectively, have Month 12 measures on 4-OHT in tissue. All baseline measures are Below Qualification Limit (BQL).

4-OHT Tissue Levels

Overall Study

Anticoagulants

Other Dietary Supplements

Citric Acid

Sodium Citrate

Citrate

Patients apply afimoxifene gel to both breasts and receive placebo PO daily for 4-10 weeks in the absence of disease progression or unexpected toxicity.

Patients apply placebo gel to both breasts and receive tamoxifen citrate orally PO daily for 4-10 weeks in the absence of disease progression or unexpected toxicity.

Tamoxifen Citrate

Principle Investigator

Seema A. Khan, MD

Joseph M. Guenther, MD

Amy C. Degnim, MD

Melissa L. Pilewskie, MD

Eun-Sil (Shelley) Hwang, MD

Stephen R. Grobmyer, MD

Seema Khan, MD

This randomized phase IIB trial studies how well tamoxifen or afimoxifene works in treating patients with estrogen receptor positive breast cancer. Estrogen can cause the growth of breast cancer cells. Hormone therapy using tamoxifen citrate or afimoxifene may fight breast cancer by blocking the use of estrogen by the tumor cells.

PRIMARY OBJECTIVES:

I. To demonstrate that 2 mg once daily per breast of 4-hydroxytamoxifen (4-OHT) topical gel results in a reduction in the Ki-67 labeling index of ductal breast carcinoma in situ (DCIS) lesions that is not inferior to that seen with 20 mg daily oral tamoxifen citrate (TAM) for 4-10 weeks, when comparing the base-line diagnostic core biopsy to the therapeutic surgical excision sample.

SECONDARY OBJECTIVES:

I. To compare post-therapy changes in the oncotype DCIS-score between arms (this is a validated reverse transcriptase-polymerase chain reaction \[RT-PCR\] assay for Ki67, STK15, survivin, cyclin B1, MYBL2, PR, GSTM1).

II. To compare between-group post-therapy changes in immunohistochemistry (IHC) markers: CD-68 macrophage marker as a surrogate for response to therapy, p16 and COX-2.

III. To compare post-therapy changes in breast density, quantitative estimate, between arms.

IV. To compare post-therapy breast tissue and plasma levels of TAM and its metabolites (N-desmethyl tamoxifen \[NDT\], \[E\] and \[Z\] isomers of 4-hydroxytamoxifen \[4-OHT\], N-desmethyl-4-hydroxytamoxifen \[endoxifen\]).

V. To compare post-therapy breast tissue and plasma levels of estradiol and progesterone between arms (optional).

VI. To compare the post-therapy fraction of participants demonstrating "no residual DCIS".

VII. To compare post-therapy changes in plasma proteins involved in coagulation: factors VIII and IX, von Willebrand factor, total protein S between arms.

VIII. To compare post-therapy changes in plasma markers of systemic estrogenic effect (IGF-1, SHBG).

IX. To compare post-therapy changes in symptoms as captured in the breast cancer prevention trial (BCPT) Eight Symptom Scale (BESS) questionnaire and skin reactions to 4-OHT gel.

OUTLINE: Patients are randomized into 1 of 2 arms.

ARM I: Patients apply afimoxifene gel to both breasts and receive placebo orally (PO) daily for 4-10 weeks in the absence of disease progression or unexpected toxicity.

ARM II: Patients apply placebo gel to both breasts and receive tamoxifen citrate orally PO daily for 4-10 weeks in the absence of disease progression or unexpected toxicity.

After completion of study treatment, patients are followed up at 1-2 weeks and 1 month after surgery.

Testing an Active Form of Tamoxifen (4-hydroxytamoxifen) Delivered Through the Breast Skin to Control Ductal Carcinoma in Situ (DCIS) of the Breast

Phase IIB Pre-Surgical Trial of Oral Tamoxifen Versus Transdermal 4-hydroxytamoxifen in Women With DCIS of the Breast

Analysis will be pilot in nature and will provide descriptive statistics for each group or subgroup of subjects, supplying results which may be used to plan future studies.

Will evaluate hot flashes, vaginal discharge/dryness, skin reactions to afimoxifene gel. Analysis will be pilot in nature and will provide descriptive statistics for each group or subgroup of subjects, supplying results which may be used to plan future studies.

BHR Pharma, LLC

4-hydroxytamoxifen gel 2mg/breast applied daily. Oral placebo taken daily.

Placebo gel applied to the breasts daily. 20mg oral tamoxifen taken daily (taken as two (2) 10mg capsules).

oral placebo

2mg/breast applied daily in the form of a gel for 4-10 weeks.

afimoxifene

20mg oral tamoxifen taken daily (taken as two (2) 10mg capsules) for 4-10 weeks.

tamoxifen citrate

Placebo gel applied to breasts daily for 4-10 weeks.

placebo gel

Seema Khan

This randomized phase II trial is studying 4-hydroxytamoxifen to see how well it works compared with tamoxifen citrate in treating women with newly diagnosed ductal breast carcinoma in situ. Estrogen can cause the growth of breast cancer cells. Hormone therapy using tamoxifen may fight breast cancer by blocking the use of estrogen by the tumor cells. It is not yet known whether topical tamoxifen causes less damage to normal tissue than systemic tamoxifen in treating patients with ductal carcinoma in situ.

This is a randomized, double-blind, placebo-controlled presurgical trial of 0.228% 4-hydroxy-tamoxifen (4-OHT) gel vs. oral tamoxifen (TAM) 20 mg daily. The study population will consist of 112 pre- and postmenopausal women with any grade DCIS, ER positive, non-palpable DCIS with no evidence of invasion found on diagnostic core needle biopsy (DCNB). In order to accrue a total of 112 participants with DCIS over a period of 22 months, 20 eligible participants total will be screened at the three participating institutions per month with a planned average monthly recruitment of 5 participants total per month. We assume that 22 women (20% of the recruited population, 11 women per arm) will be inevaluable because of the presence of unanticipated invasive disease in the therapeutic surgical excisional (TSE) specimen, or the absence of residual DCIS in the TSE, so that a total of 90 women (45 per arm) will be evaluable for the study endpoints. These estimates are based on numbers from the Lynn Sage Database of NU: over the six-year period 2000-2005, the fraction of women diagnosed with DCIS on core needle biopsy who were found to have no residual DCIS in the TSE was 2.5% and that of women with invasive disease (T1a or greater) in the TSE when the DCNB showed pure DCIS was 13.3%, very similar to the data reported by Bonnett et. al. \[56\] who found that 13% of pure DCIS lesions seen on DCNB (29/122) were in fact invasive in the TSE. With regard to racial/ethnic groups, 25.6% of the DCIS population at NU were of non-European ancestry (18% African, 4% Hispanic, 3.5% other). WU has higher fractions of African American women with DCIS (24% and 21% respectively).

The participants will be consented following diagnostic core needle biopsy at the time of initial surgical consultation. Baseline assessments include medical history, nipple aspirate fluid (NAF) collection, explanation of gel application, BESS questionnaire (symptom assessment) and blood draw for clinical and research labs including plasma estradiol, progesterone and FSH (rushed), CBC, chemistry profile, liver and renal function tests, Factor VIII, von Willebrand Factor, Factor IX, and total protein S, plasma for insulin-like growth factor (IGF-1) and sex hormone-binding globulin (SHBG), and DNA extraction for assessment of polymorphisms in tamoxifen metabolism genes. At Northwestern plasma and RNA from blood will be collected pre- and post-treatment and will be stored for future proteomic and gene expression fingerprinting

No run-in period is planned. The intervention phase will begin within 5 days following randomization and end on the day prior to surgical resection. The 4-OHT group will apply active gel 2 mg daily to each breast for 4-10 weeks and take oral placebo. The TAM group will take 20 mg TAM orally daily and apply gel placebo. The last dose of study medication will be used on the morning of the day prior to surgery.

Participants will be shipped two 100 ml canisters of 4-OHT or placebo gel plus 130 capsules of tamoxifen or oral placebo at the time of randomization. Participants will take study agents for 4-10 week (minimum). However, if surgery needs to be delayed beyond the 8 week study period for clinical reasons (eg scheduling with plastic surgery) the participant will be sent additional medication by mail to allow continuation of therapy until the day before surgery up to a maximum duration of 10 weeks.

On the day prior to surgery, baseline assessments will be repeated (with the exception of menopausal determination and tamoxifen metabolism gene polymorphisms, but with the addition of blood draw for tamoxifen metabolites and E and Z 4-OHT isomer determination). Under unavoidable circumstances, the end of intervention visit will be allowed on the day of surgery prior to TSE. During the TSE breast adipose tissue from the surgical sample will be snap frozen and stored at -800C for measurement of TAM metabolites. The paraffin block of the DCNB and TSE samples will be acquired by the recruiting institution and 10 sections from each specimen submitted to the NU Pathology Core Facility (NU PCF). The sections will be cut in batches (with pre- and post-samples in the same batch), shipped cold, and processed for immunohistochemistry within a week of sectioning.

Compliance assessment will occur through patient diaries, pill counts and the weighing of returned drug (gel) canisters.

Patients will be assessed for adverse events at the post-surgical visit (approximately 7-14 days after surgery) and by phone at 30 days following the last dose of study agent.

4-Hydroxytamoxifen or Tamoxifen Citrate in Treating Women With Newly Diagnosed Ductal Breast Carcinoma in Situ

Pre-surgical Phase IIb Trial of Transdermal 4-Hydroxytamoxifen vs. Oral Tamoxifen in Women With Ductal Carcinoma in Situ of the Breast

Concentrations of tamoxifen and its metabolites: 4-hydroxytamoxifen, endoxifen, and NDT were measured in breast tissue, blood, and Nipple Aspirate Fluid (NAF) that was collected on the day of surgery.

Descriptive statistics and confidence intervals will be provided.

Ki-67 was measured in matched core and excision tissue samples containing DCIS (Ductal Carcinoma In-Situ) lesions, the core sample was at baseline while the excision sample was at surgery (after approximately 4-10 weeks of treatment).

Hot flashes were assessed by the Breast Cancer Prevention Trial Eight Symptom Scale (BESS) questionnaire. This questionnaire measures the incidence of a number of symptoms by asking participants how frequently they experienced them on a scale of 0-4 (0 being Not at All and 4 being Extremely often). BESS questionnaire was administered at baseline and time of surgery. The incidence of vasomotor symptoms (including hot flashes, night sweats, and cold sweats) was measured at baseline (Day 0) and end of treatment prior to surgery (at least 4 weeks later or up to 10 weeks, depending on scheduled surgery date), and changes in the mean score for hot flashes were observed.

The difference between vWF coagulation protein in blood samples collected at baseline and before surgery were measured using the immune-turbidimetric assay.

The difference between Factor VIII coagulation protein in blood samples collected at baseline and before surgery was measured with VisuLize antigen ELISA Kits.

The difference between Factor IX coagulation protein in blood samples collected at baseline and before surgery was measured with VisuLize antigen ELISA Kits.

The difference between protein S coagulation protein in blood samples collected at baseline and before surgery was measured using an ELISA Kit.

Professor

Patients were asked about any adverse events they may have experienced at every study visit.

4-hydroxytamoxifen gel 2mg/breast applied daily. Oral placebo taken daily.

oral placebo: Oral placebo taken daily for 4-10 weeks.

afimoxifene: 2mg/breast applied daily in the form of a gel for 4-10 weeks.

Treatment Gel + Oral Placebo

Placebo gel applied to the breasts daily. 20mg oral tamoxifen taken daily (taken as two (2) 10mg capsules).

tamoxifen citrate: 20mg oral tamoxifen taken daily (taken as two (2) 10mg capsules) for 4-10 weeks.

placebo gel: Placebo gel applied to breasts daily for 4-10 weeks.

Placebo Gel + Oral Treatment

40-49 years

50-59 years

60-69 years

70-79 years

80-89 years

Age, Customized

Pre-Menopausal

Post-Menopausal

Menopausal status

The study was originally designed to enroll 112 participants, unfortunately, the shelf-life of the study drug expired which resulted in early closure of the study after only 31 participants.

Dr. Seema Khan

18 total subjects were evaluable for immunohistochemistry marker testing including the Ki-67 labeling index. Of the 26 participants who completed study treatment 2 did not have matching samples available for testing and 6 were excluded because of insufficient DCIS lesion in their samples for testing.

Difference Between Ki-67 Labeling Index in Tissue Samples Taken at Baseline and Post-treatment

Compare Concentrations of Tamoxifen and Its Metabolites (4-hydroxytamoxifen, Endoxifen, N-desmethyl Tamoxifen (NDT)) Obtained From Samples on the Day of Surgery

Drug Metabolite Levels in the Two Study Groups by CYP2D6 Polymorphism Status

4-OHT Affects Known Tamoxifen-modulated Pathways

TAM Metabolite Concentrations and Estrogen Response Markers in Nipple Aspiration Fluid (NAF)

1 patient who did not complete the treatment period due expired drug supply was not evaluable for this outcome measure.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Topical Afimoxifene in Treating Patients With Breast Cancer Who Have Undergone Radiation Therapy on One Breast	NCT04009044	Cancer Survivor Ductal Breast C... Invasive Breast...	Afimoxifene Core Biopsy Questionnaire A...	18 Years -	Northwestern University
Afimoxifene in Reducing the Risk of Breast Cancer in Women With Mammographically Dense Breast	NCT03063619	Mammographicall...	Afimoxifene Laboratory Biom... Placebo Questionnaire A...	40 Years - 69 Years	M.D. Anderson Cancer Center
Topical Afimoxifene in Treating Patients With Breast Cancer Who Have Undergone Radiation Therapy on One Breast	NCT04009044	Cancer Survivor Ductal Breast C... Invasive Breast...	Afimoxifene Core Biopsy Questionnaire A...	18 Years -	Northwestern University
Testing an Active Form of Tamoxifen (4-hydroxytamoxifen) Delivered Through the Breast Skin to Control Ductal Carcinoma in Situ (DCIS) of the Breast	NCT02993159	Ductal Breast C... Estrogen Recept...	Afimoxifene Laboratory Biom... Placebo Placebo Tamoxifen Citra...	18 Years -	Northwestern University
4-Hydroxytamoxifen or Tamoxifen Citrate in Treating Women With Newly Diagnosed Ductal Breast Carcinoma in Situ	NCT00952731	Ductal Breast C... Estrogen Recept...	oral placebo afimoxifene tamoxifen citra... placebo gel	18 Years -	Northwestern University

Spots Global Cancer Trial Database for afimoxifene

Every month we try and update this database with for afimoxifene cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for afimoxifene

Every month we try and update this database with for afimoxifene cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for afimoxifene cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.