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
Conditions
Brief summary
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
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.
Interventions
Given transdermally
OTHERPlacebo
Given PO
OTHERLaboratory Biomarker Analysis
Correlative studies
OTHERQuestionnaire Administration
Ancillary studies
Sponsors
National Cancer Institute (NCI)
Northwestern University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Levels of Telapristone Acetate in Breast Tissue | At the time of mastectomy, up to 5 weeks from baseline | Post-therapy mean levels of telapristone acetate in breast tissue. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Within-breast Variation of Breast Tissue Concentration of Telapristone Acetate | At the time of mastectomy, up to 5 weeks from baseline | Post-therapy concentrations of telapristone acetate in 5 locations within breast tissue. |
| Changes in Serum Sex Hormone Concentrations: Estradiol | Baseline to mastectomy, up to 5 weeks post-intervention | Change in estradiol in premenopausal women from baseline to post-intervention compared between treatment groups |
| Changes in Cell Proliferation | Baseline to mastectomy (up to 5 weeks) | Changes in cell proliferation (Ki67 labeling index) measured in percentage of positive cells from baseline to mastectomy by tumor status in ER positive tumors. |
| Plasma Concentrations of Telapristone Acetate | At the time of mastectomy, up to 5 weeks from baseline | Post-therapy plasma concentrations of telapristone acetate. |
| Changes in Serum Sex Hormone Concentrations: Progesterone | Baseline to mastectomy (up to 5 weeks) | Change in progesterone in premenopausal women from baseline to post-intervention compared between treatment groups |
| Changes in Serum Sex Hormone Concentrations: FSH | Baseline to mastectomy (up to 5 weeks) | Change in FSH in premenopausal women from baseline to post-intervention compared between treatment groups |
| Change in Symptoms as Captured in the Breast Cancer Prevention Trial (BCPT) Eight Symptom Scale (BESS) Questionnaire | Baseline to mastectomy (up to 5 weeks) | 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm I (Transdermal Telapristone Acetate) Participants receive telapristone acetate transdermally and placebo PO QD for 4 weeks.
Telapristone Acetate: Given transdermally applied to both breast skin
Placebo: Given PO | 33 |
| Arm II (Oral Telapristone Acetate) Patients receive placebo transdermally and telapristone acetate PO QD for 4 weeks.
Telapristone Acetate: Given PO
Placebo: Given transdermally applied to both breast skin | 34 |
| Total | 67 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Arm I (Transdermal Telapristone Acetate) | Total | Arm II (Oral Telapristone Acetate) |
|---|---|---|---|
| Age, Continuous | 48.0 years STANDARD_DEVIATION 9.27 | 48.6 years STANDARD_DEVIATION 11.5 | 49.3 years STANDARD_DEVIATION 13.41 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 7 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 29 Participants | 58 Participants | 29 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 7 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 6 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 27 Participants | 53 Participants | 26 Participants |
| Region of Enrollment United States | 33 participants | 67 participants | 34 participants |
| Sex: Female, Male Female | 33 Participants | 67 Participants | 34 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 33 | 0 / 34 |
| other Total, other adverse events | 25 / 33 | 21 / 34 |
| serious Total, serious adverse events | 0 / 33 | 0 / 34 |
Outcome results
Primary
Mean Levels of Telapristone Acetate in Breast Tissue
Post-therapy mean levels of telapristone acetate in breast tissue.
Time frame: At the time of mastectomy, up to 5 weeks from baseline
Population: Participants with post-therapy breast tissue samples
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I (Transdermal Telapristone Acetate) | Mean Levels of Telapristone Acetate in Breast Tissue | 2.82 ng/g |
| Arm II (Oral Telapristone Acetate) | Mean Levels of Telapristone Acetate in Breast Tissue | 103 ng/g |
Secondary
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
Time frame: Baseline to mastectomy (up to 5 weeks)
Population: participants
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm I (Transdermal Telapristone Acetate) | Change in Symptoms as Captured in the Breast Cancer Prevention Trial (BCPT) Eight Symptom Scale (BESS) Questionnaire | Bladder | -0.32 score on a scale | Standard Error 0.18 |
| Arm I (Transdermal Telapristone Acetate) | Change in Symptoms as Captured in the Breast Cancer Prevention Trial (BCPT) Eight Symptom Scale (BESS) Questionnaire | Body Pain | -0.81 score on a scale | Standard Error 0.44 |
| Arm I (Transdermal Telapristone Acetate) | Change in Symptoms as Captured in the Breast Cancer Prevention Trial (BCPT) Eight Symptom Scale (BESS) Questionnaire | Vasomotor | 0.71 score on a scale | Standard Error 0.26 |
| Arm I (Transdermal Telapristone Acetate) | Change in Symptoms as Captured in the Breast Cancer Prevention Trial (BCPT) Eight Symptom Scale (BESS) Questionnaire | Gastrointestinal | 0.16 score on a scale | Standard Error 0.35 |
| Arm I (Transdermal Telapristone Acetate) | Change in Symptoms as Captured in the Breast Cancer Prevention Trial (BCPT) Eight Symptom Scale (BESS) Questionnaire | Sexual problems | -0.29 score on a scale | Standard Error 0.24 |
| Arm I (Transdermal Telapristone Acetate) | Change in Symptoms as Captured in the Breast Cancer Prevention Trial (BCPT) Eight Symptom Scale (BESS) Questionnaire | Body Image | 0.52 score on a scale | Standard Error 0.34 |
| Arm I (Transdermal Telapristone Acetate) | Change in Symptoms as Captured in the Breast Cancer Prevention Trial (BCPT) Eight Symptom Scale (BESS) Questionnaire | Vaginal | -0.35 score on a scale | Standard Error 0.2 |
| Arm I (Transdermal Telapristone Acetate) | Change in Symptoms as Captured in the Breast Cancer Prevention Trial (BCPT) Eight Symptom Scale (BESS) Questionnaire | Cognitive | -0.61 score on a scale | Standard Error 0.53 |
| Arm II (Oral Telapristone Acetate) | Change in Symptoms as Captured in the Breast Cancer Prevention Trial (BCPT) Eight Symptom Scale (BESS) Questionnaire | Sexual problems | -0.28 score on a scale | Standard Error 0.19 |
| Arm II (Oral Telapristone Acetate) | Change in Symptoms as Captured in the Breast Cancer Prevention Trial (BCPT) Eight Symptom Scale (BESS) Questionnaire | Cognitive | -0.88 score on a scale | Standard Error 0.43 |
| Arm II (Oral Telapristone Acetate) | Change in Symptoms as Captured in the Breast Cancer Prevention Trial (BCPT) Eight Symptom Scale (BESS) Questionnaire | Bladder | -0.38 score on a scale | Standard Error 0.18 |
| Arm II (Oral Telapristone Acetate) | Change in Symptoms as Captured in the Breast Cancer Prevention Trial (BCPT) Eight Symptom Scale (BESS) Questionnaire | Body Pain | -0.78 score on a scale | Standard Error 0.43 |
| Arm II (Oral Telapristone Acetate) | Change in Symptoms as Captured in the Breast Cancer Prevention Trial (BCPT) Eight Symptom Scale (BESS) Questionnaire | Vaginal | 0.19 score on a scale | Standard Error 0.27 |
| Arm II (Oral Telapristone Acetate) | Change in Symptoms as Captured in the Breast Cancer Prevention Trial (BCPT) Eight Symptom Scale (BESS) Questionnaire | Vasomotor | 0.09 score on a scale | Standard Error 0.23 |
| Arm II (Oral Telapristone Acetate) | Change in Symptoms as Captured in the Breast Cancer Prevention Trial (BCPT) Eight Symptom Scale (BESS) Questionnaire | Body Image | -0.16 score on a scale | Standard Error 0.25 |
| Arm II (Oral Telapristone Acetate) | Change in Symptoms as Captured in the Breast Cancer Prevention Trial (BCPT) Eight Symptom Scale (BESS) Questionnaire | Gastrointestinal | -0.34 score on a scale | Standard Error 0.11 |
Secondary
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.
Time frame: Baseline to mastectomy (up to 5 weeks)
Population: Participants with ER positive tumors.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I (Transdermal Telapristone Acetate) | Changes in Cell Proliferation | -0.67 % positive |
| Arm II (Oral Telapristone Acetate) | Changes in Cell Proliferation | 5.2 % positive |
Secondary
Changes in Serum Sex Hormone Concentrations: Estradiol
Change in estradiol in premenopausal women from baseline to post-intervention compared between treatment groups
Time frame: Baseline to mastectomy, up to 5 weeks post-intervention
Population: Premenopausal women
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I (Transdermal Telapristone Acetate) | Changes in Serum Sex Hormone Concentrations: Estradiol | 95.9 pg/ml |
| Arm II (Oral Telapristone Acetate) | Changes in Serum Sex Hormone Concentrations: Estradiol | -23.7 pg/ml |
Secondary
Changes in Serum Sex Hormone Concentrations: FSH
Change in FSH in premenopausal women from baseline to post-intervention compared between treatment groups
Time frame: Baseline to mastectomy (up to 5 weeks)
Population: Premenopausal women
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I (Transdermal Telapristone Acetate) | Changes in Serum Sex Hormone Concentrations: FSH | 1.91 mIU |
| Arm II (Oral Telapristone Acetate) | Changes in Serum Sex Hormone Concentrations: FSH | 0.30 mIU |
Secondary
Changes in Serum Sex Hormone Concentrations: Progesterone
Change in progesterone in premenopausal women from baseline to post-intervention compared between treatment groups
Time frame: Baseline to mastectomy (up to 5 weeks)
Population: Premenopausal women
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I (Transdermal Telapristone Acetate) | Changes in Serum Sex Hormone Concentrations: Progesterone | 0.19 ng/ml |
| Arm II (Oral Telapristone Acetate) | Changes in Serum Sex Hormone Concentrations: Progesterone | -2.36 ng/ml |
Secondary
Plasma Concentrations of Telapristone Acetate
Post-therapy plasma concentrations of telapristone acetate.
Time frame: At the time of mastectomy, up to 5 weeks from baseline
Population: Participants with plasma samples post-therapy.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I (Transdermal Telapristone Acetate) | Plasma Concentrations of Telapristone Acetate | 0.93 ng/ml |
| Arm II (Oral Telapristone Acetate) | Plasma Concentrations of Telapristone Acetate | 69.0 ng/ml |
Secondary
Within-breast Variation of Breast Tissue Concentration of Telapristone Acetate
Post-therapy concentrations of telapristone acetate in 5 locations within breast tissue.
Time frame: At the time of mastectomy, up to 5 weeks from baseline
Population: Participants with post-therapy breast tissue samples.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Arm I (Transdermal Telapristone Acetate) | Within-breast Variation of Breast Tissue Concentration of Telapristone Acetate | Lateral Surface | 6.76 ng/g |
| Arm I (Transdermal Telapristone Acetate) | Within-breast Variation of Breast Tissue Concentration of Telapristone Acetate | Medial Center | 2.79 ng/g |
| Arm I (Transdermal Telapristone Acetate) | Within-breast Variation of Breast Tissue Concentration of Telapristone Acetate | Lateral Center | 2.42 ng/g |
| Arm I (Transdermal Telapristone Acetate) | Within-breast Variation of Breast Tissue Concentration of Telapristone Acetate | Central Subalveolar | 1.73 ng/g |
| Arm I (Transdermal Telapristone Acetate) | Within-breast Variation of Breast Tissue Concentration of Telapristone Acetate | Central Deepest | 5.09 ng/g |
| Arm II (Oral Telapristone Acetate) | Within-breast Variation of Breast Tissue Concentration of Telapristone Acetate | Central Subalveolar | 63.7 ng/g |
| Arm II (Oral Telapristone Acetate) | Within-breast Variation of Breast Tissue Concentration of Telapristone Acetate | Central Deepest | 133 ng/g |
| Arm II (Oral Telapristone Acetate) | Within-breast Variation of Breast Tissue Concentration of Telapristone Acetate | Lateral Surface | 214 ng/g |
| Arm II (Oral Telapristone Acetate) | Within-breast Variation of Breast Tissue Concentration of Telapristone Acetate | Lateral Center | 85.5 ng/g |
| Arm II (Oral Telapristone Acetate) | Within-breast Variation of Breast Tissue Concentration of Telapristone Acetate | Medial Center | 121 ng/g |