Transdermal or Oral Telapristone Acetate in Treating Patients Undergoing Mastectomy

Study Overview
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Brief Summary
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This randomized trial studies transdermal or oral telapristone acetate in treating patients undergoing surgery to remove the breast (mastectomy). Telapristone acetate may help prevent breast cancer from forming in premenopausal women. Giving telapristone acetate transdermally may be safer and have fewer side effects than oral administration.

Detailed Description
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PRIMARY OBJECTIVES: I. To demonstrate that mean levels of telapristone (telapristone acetate) in breast tissue following gel application will result in levels that are not more than 50% lower than those following oral administration. SECONDARY OBJECTIVES: I. To assess whether plasma concentrations of telapristone are significantly lower with transdermal than oral therapy. II. To compare within-breast variation of breast tissue concentration in transdermal and oral groups. III. To measure changes in cell proliferation (marker of proliferation (Ki-67 labeling index). IV. Explore changes in gene expression in breast tissue related to telapristone therapy. V. Assess change in serum progesterone associated with telapristone therapy. VI. Assess the safety and tolerability of oral and transdermal administration. VII. Assess symptom measurements using BESS Questionnaire OUTLINE: Participants are randomized to 1 of 2 treatment arms. ARM I (TRANSDERMAL TELAPRISTONE ACETATE): Patients receive telapristone acetate transdermally and placebo orally (PO) once daily (QD) for 4 weeks. ARM II (ORAL TELAPRISTONE ACETATE): Patients receive placebo transdermally and telapristone acetate PO QD for 4 weeks. After completion of study treatment, patients are followed up at day 60.

Official Title
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Intra-mammary Distribution of Transdermal Telapristone Versus Oral Telapristone: A Randomized Window Trial in Women Undergoing Mastectomy

Conditions
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BRCA1 Mutation Carrier, BRCA2 Mutation Carrier, Ductal Breast Carcinoma In Situ, Lobular Breast Carcinoma In Situ, Stage 0 Breast Cancer, Stage IA Breast Cancer, Stage IB Breast Cancer, Stage IIA Breast Cancer, Stage IIB Breast Cancer

Intervention / Treatment
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* Drug: Telapristone Acetate
* Other: Placebo
* Drug: Telapristone Acetate
* Other: Placebo
* Other: Laboratory Biomarker Analysis
* Other: Questionnaire Administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women scheduled for unilateral or bilateral mastectomy for breast cancer therapy, pathology confirmed stage 0-II (including ductal carcinoma in situ), or prophylaxis (breast cancer, early onset [BRCA] mutation carriers, women with strong family history or lobular carcinoma in situ or other conditions where prophylactic mastectomy has been elected) Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%) Total bilirubin < 1.5 x upper limit of normal (ULN) Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) < 2.5 x ULN Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 2.5 x ULN Creatinine < 2 x ULN Alkaline phosphatase < 2.5 x ULN Blood urea nitrogen < 2 x ULN Willing to use non-hormonal contraception (adequate barrier-type contraception or intrauterine device [IUD]) from the time the pregnancy test is performed for the duration of study participation, and 30 days after study drug cessation (for women of childbearing potential only) Ability to understand and the willingness to sign a written informed consent document Willing and able to schedule mastectomy 4 weeks (+/- 7days) following start of study agent Willing to avoid exposing breast skin to natural or artificial sunlight (i.e. tanning beds) for the duration of study agent dosing Negative urine pregnancy test result, for participants of child bearing potential, within 5 days prior to first dose of study medication; female of child-bearing potential is any woman (regardless of sexual orientation, whether she has undergone a tubal ligation, or remains celibate by choice) who meets the following criteria: has not undergone a hysterectomy or bilateral oophorectomy; OR has had a menstrual period at any time in the preceding 12 consecutive months) Willing to use alcohol in moderation while taking study agent Exclusion Criteria: The presence of skin invasion by the breast cancer, or inflammatory changes with skin edema AND erythema. Note: Paget's disease is permitted. Women receiving a nipple delay procedure prior to mastectomy. Women with skin diseases (psoriasis, eczema) on breast. A history of thromboembolic disorder or cerebral vascular disease Use of oral contraceptives or other hormonal treatments within eight weeks prior to the randomization or during the period of the study; women should not have used Depo-Provera in the preceding 6 months; use of hormone coated IUD like Mirena is allowed Participants may not have received any other investigational agents in the previous 3 months History of allergic reactions attributed to compounds of similar chemical or biologic composition to telapristone (i.e. other progesterone antagonists) Taken tamoxifen or other selective estrogen/progesterone receptor modulators (SERMs/SPRMs) within two years prior to entering study or been required to discontinue SERM therapy due to thromboembolic or uterine toxicity Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements History of prior breast cancer-specific therapy within the previous 2 years; previous unilateral radiation in women scheduled for mastectomy of the contralateral side is allowed Pregnant or breastfeeding Currently taking spironolactone Recent history (within 6 months) of alcoholism or drug abuse Known active infection with human immunodeficiency virus (HIV), hepatitis A, B, or C

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (transdermal telapristone acetate)<br>Patients receive telapristone acetate transdermally and placebo PO QD for 4 weeks. | Drug: Telapristone Acetate<br>* Given transdermally<br>* Other names: Progenta;Other: Placebo<br>* Given PO<br>* Other names: PLCB;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Other: Questionnaire Administration<br>* Ancillary studies<br>|
| Active Comparator: Arm II (oral telapristone acetate)<br>Patients receive placebo transdermally and telapristone acetate PO QD for 4 weeks. | Drug: Telapristone Acetate<br>* Given PO<br>* Other names: Progenta;Other: Placebo<br>* Given transdermally<br>* Other names: PLCB;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Other: Questionnaire Administration<br>* Ancillary studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Levels of Telapristone Acetate in Breast Tissue | Post-therapy mean levels of telapristone acetate in breast tissue. | At the time of mastectomy, up to 5 weeks from baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Concentrations of Telapristone Acetate | Post-therapy plasma concentrations of telapristone acetate. | At the time of mastectomy, up to 5 weeks from baseline | 
| Within-breast Variation of Breast Tissue Concentration of Telapristone Acetate | Post-therapy concentrations of telapristone acetate in 5 locations within breast tissue. | At the time of mastectomy, up to 5 weeks from baseline | 
| Changes in Cell Proliferation | Changes in cell proliferation (Ki67 labeling index) measured in percentage of positive cells from baseline to mastectomy by tumor status in ER positive tumors. | Baseline to mastectomy (up to 5 weeks) | 
| Changes in Serum Sex Hormone Concentrations: Estradiol | Change in estradiol in premenopausal women from baseline to post-intervention compared between treatment groups | Baseline to mastectomy, up to 5 weeks post-intervention | 
| Change in Symptoms as Captured in the Breast Cancer Prevention Trial (BCPT) Eight Symptom Scale (BESS) Questionnaire | Mean change in symptoms as captured using the Breast Cancer Prevention Trial (BCPT) Eight Symptom Scale (BESS) questionnaire. A patient reported outcome, scores range from 0 (Not at All) to 4 (Extremely) when asked about experiencing symptoms. A positive change in scores indicates an increase in symptoms experienced and a negative change in scores indicates a decrease in symptoms experienced | Baseline to mastectomy (up to 5 weeks) | 
| Changes in Serum Sex Hormone Concentrations: Progesterone | Change in progesterone in premenopausal women from baseline to post-intervention compared between treatment groups | Baseline to mastectomy (up to 5 weeks) | 
| Changes in Serum Sex Hormone Concentrations: FSH | Change in FSH in premenopausal women from baseline to post-intervention compared between treatment groups | Baseline to mastectomy (up to 5 weeks) |