Transdermal or Oral Telapristone Acetate in Treating Patients Undergoing Mastectomy

Phase 2

Completed

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

Interventions: Drug: Telapristone Acetate
Other: Placebo
Other: Laboratory Biomarker Analysis
Other: Questionnaire Administration

Registration Number: NCT02314156

Lead Sponsor: Northwestern University

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 67

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (transdermal telapristone acetate)	Placebo	Patients receive telapristone acetate transdermally and placebo PO QD for 4 weeks.
Arm II (oral telapristone acetate)	Laboratory Biomarker Analysis	Patients receive placebo transdermally and telapristone acetate PO QD for 4 weeks.
Arm I (transdermal telapristone acetate)	Questionnaire Administration	Patients receive telapristone acetate transdermally and placebo PO QD for 4 weeks.
Arm II (oral telapristone acetate)	Placebo	Patients receive placebo transdermally and telapristone acetate PO QD for 4 weeks.
Arm I (transdermal telapristone acetate)	Laboratory Biomarker Analysis	Patients receive telapristone acetate transdermally and placebo PO QD for 4 weeks.
Arm II (oral telapristone acetate)	Questionnaire Administration	Patients receive placebo transdermally and telapristone acetate PO QD for 4 weeks.
Arm II (oral telapristone acetate)	Telapristone Acetate	Patients receive placebo transdermally and telapristone acetate PO QD for 4 weeks.
Arm I (transdermal telapristone acetate)	Telapristone Acetate	Patients receive telapristone acetate transdermally and placebo PO QD for 4 weeks.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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 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.
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
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
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 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

Trial Locations

Locations (3): Cedars-Sinai Medical Center
🇺🇸
West Hollywood, California, United States
Northwestern University
🇺🇸
Chicago, Illinois, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸
New York, New York, United States
Cedars-Sinai Medical Center
🇺🇸West Hollywood, California, United States