Transdermal or Oral Telapristone Acetate in Treating Patients Undergoing Mastectomy

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

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.

Study Overview

• Status: Completed
• Conditions: Stage 0 Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Lobular Breast Carcinoma In Situ; Ductal Breast Carcinoma In Situ; BRCA1 Mutation Carrier; BRCA2 Mutation Carrier
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Other: Placebo; Other: Questionnaire Administration; Drug: Telapristone Acetate; Drug: Telapristone Acetate; Other: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 67
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • West Hollywood, California, United States, 90048
      • Cedars-Sinai Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (transdermal telapristone acetate); Patients receive telapristone acetate transdermally and placebo PO QD for 4 weeks.	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Placebo; Given PO; Other Names: PLCB; Other: Questionnaire Administration; Ancillary studies; Drug: Telapristone Acetate; Given transdermally; Other Names: CDB-4124; Proellex; Progenta; Drug: Telapristone Acetate; Given PO; Other Names: CDB-4124; Proellex; Progenta; Other: Placebo; Given transdermally; Other Names: PLCB
Active Comparator: Arm II (oral telapristone acetate); Patients receive placebo transdermally and telapristone acetate PO QD for 4 weeks.	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Placebo; Given PO; Other Names: PLCB; Other: Questionnaire Administration; Ancillary studies; Drug: Telapristone Acetate; Given transdermally; Other Names: CDB-4124; Proellex; Progenta; Drug: Telapristone Acetate; Given PO; Other Names: CDB-4124; Proellex; Progenta; Other: Placebo; Given transdermally; Other Names: PLCB

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Northwestern University
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2015
• Primary Completion (Actual): January 1, 2018
• Study Completion (Actual): May 1, 2021

Study Registration Dates

• First Submitted: December 9, 2014
• First Submitted That Met QC Criteria: December 10, 2014
• First Posted (Estimate): December 11, 2014

Study Record Updates

• Last Update Posted (Estimate): February 22, 2023
• Last Update Submitted That Met QC Criteria: January 26, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Breast Diseases; Neoplasms, Ductal, Lobular, and Medullary; Carcinoma, Ductal; Carcinoma in Situ; Breast Neoplasms; Carcinoma; Breast Carcinoma In Situ; Carcinoma, Intraductal, Noninfiltrating; Carcinoma, Lobular; Carcinoma, Ductal, Breast
• Other Study ID Numbers: NCI 2013-01-03 (Other Identifier: Northwestern University); N01-CN-2012-00035; NCI-2014-02412 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); NWU2013-01-03 (Other Identifier: DCP); HHSN26100003 (Other Grant/Funding Number: National Cancer Institute)