Transdermal or Oral Telapristone Acetate in Treating Patients Undergoing Mastectomy
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
PRIMARY OBJECTIVES:
- 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:
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To assess whether plasma concentrations of telapristone are significantly lower with transdermal than oral therapy.
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To compare within-breast variation of breast tissue concentration in transdermal and oral groups.
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To measure changes in cell proliferation (marker of proliferation Ki-67 [Ki67] labeling index) and apoptosis (terminal deoxynucleotidyl transferase deoxyuridine triphosphate [dUTP] nick end labeling [TUNEL]) in breast cancer samples obtained at diagnostic core needle biopsy (of cancer) or research core needle biopsy (of unaffected breast) with tissue samples obtained at mastectomy. Measure protein expression of related targets in the following order of priority: progesterone receptor isoforms (progesterone receptor [PR]A and PRB), and estrogen receptor alpha (ERα) and TUNEL using immunohistochemistry (IHC) at baseline and after treatment.
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Explore changes in gene expression in breast tissue related to telapristone therapy.
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Assess change in serum progesterone associated with telapristone therapy. VI. Assess the safety and tolerability of oral and transdermal administration.
OUTLINE: Patients 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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Arm I (transdermal telapristone acetate) Patients receive telapristone acetate transdermally and placebo PO QD for 4 weeks. |
Drug: Telapristone Acetate
Given transdermally
Other Names:
Other: Placebo
Given PO
Other Names:
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Questionnaire Administration
Ancillary studies
|
| Active Comparator: Arm II (oral telapristone acetate) Patients receive placebo transdermally and telapristone acetate PO QD for 4 weeks. |
Drug: Telapristone Acetate
Given PO
Other Names:
Other: Placebo
Given transdermally
Other Names:
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Questionnaire Administration
Ancillary studies
|
Outcome Measures
Primary Outcome Measures
- Mean levels of telapristone acetate in breast tissue [At the time of mastectomy]
Will be compared between the two arms to demonstrate that mean levels of 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 Outcome Measures
- Plasma concentrations of telapristone acetate [At the time of mastectomy]
Will be compared between arms to assess whether plasma concentrations of telapristone acetate are significantly lower with transdermal than oral therapy.
- Within-breast variation of breast tissue concentration of telapristone acetate [At the time of mastectomy]
Within-breast variation of breast tissue concentration in transdermal and oral groups will be assessed/
- Changes in cell proliferation and apoptosis [From diagnosis to time of mastectomy]
Changes in cell proliferation (Ki67 labeling index) and apoptosis (TUNEL) in breast cancer samples obtained at diagnostic core needle biopsy (of cancer) or research core needle biopsy (of unaffected breast) with tissue samples obtained at mastectomy will be assessed. Measure protein expression of related targets in the following order of priority progesterone receptor isoforms (PRA and PRB), ERα, using IHC at baseline and after treatment.
- Changes in gene expression [From diagnosis to the time of mastectomy]
Will be measured to identify treatment response. Breast tissue samples will be used for expression arrays and subjected to the confirmatory measurements of messenger ribonucleic acid (mRNA) expression using nanostring for selected genes (tumor necrosis factor receptor superfamily, member 11a, nuclear factor kappa B [NFKB] activator [RANK], tumor necrosis factor [ligand] superfamily, member 11 [RANKL], prolactin receptor, cyclin D1) and for additional genes selected from the array experiments.
- Change in serum progesterone [Baseline to the time of mastectomy]
- Incidence of adverse events, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [Up to day 40]
Assessed for oral and transdermal administration.
Eligibility Criteria
Criteria
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)
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Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
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Total bilirubin < 1.5 x upper limit of normal (ULN)
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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
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Alkaline phosphatase < 2.5 x ULN
-
Blood urea nitrogen < 2 x ULN
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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)
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Ability to understand and the willingness to sign a written informed consent document
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Willing and able to schedule mastectomy 4 weeks (+/- 7days) following start of study agent
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Willing to avoid exposing breast skin to natural or artificial sunlight (i.e. tanning beds) for the duration of study agent dosing
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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)
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Willing to use alcohol in moderation while taking study agent
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Willing to refrain from using soy supplements, over the counter estrogen supplements like estroven, Chinese herbs, or other over-the-counter (OTC) herbal products
Exclusion Criteria:
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The presence of skin invasion by the breast cancer, or inflammatory changes with skin edema AND erythema
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Women with skin diseases (psoriasis, eczema)
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A history of thromboembolic disorder or cerebral vascular disease
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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
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Participants may not have received any other investigational agents in the previous 3 months
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History of allergic reactions attributed to compounds of similar chemical or biologic composition to telapristone (i.e. other progesterone antagonists)
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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
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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
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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
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Pregnant or breastfeeding
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Currently taking spironolactone
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Recent history (within 6 months) of alcoholism or drug abuse
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Known active infection with human immunodeficiency virus (HIV), hepatitis A, B, or C
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Cedars-Sinai Medical Center | West Hollywood | California | United States | 90048 |
| 2 | Northwestern University | Chicago | Illinois | United States | 60611 |
| 3 | Memorial Sloan-Kettering Cancer Center | New York | New York | United States | 10065 |
Sponsors and Collaborators
- Northwestern University
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Seema Khan, Northwestern University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NCI 2013-01-03
- NCI-2014-02412
- N01-CN-2012-00035
- HHSN2612201200035I
- NCI 2013-01-03
- NWU2013-01-03
- R43CA091483
- P30CA060553
- N01CN00035