Transdermal or Oral Telapristone Acetate in Treating Patients Undergoing Mastectomy

Stage IB Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02314156
• Other study ID #: NCI 2013-01-03
• Secondary ID: NCI-2014-02412N0
• Status: Completed
• Phase: Phase 2
• Start date: October 2015
• Est. completion date: May 2021

Study information

• Verified date: January 2023
• Source: Northwestern University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 67
• Est. completion date: May 2021
• Est. primary completion date: January 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• BRCA1 Mutation Carrier
• BRCA2 Mutation Carrier
• Breast Carcinoma In Situ
• Breast Neoplasms
• Carcinoma
• Carcinoma in Situ
• Carcinoma, Ductal, Breast
• Carcinoma, Intraductal, Noninfiltrating
• Carcinoma, Lobular
• 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

Drug:
• Telapristone Acetate
Given transdermally

Other:
• Placebo
Given PO

Drug:
• Telapristone Acetate
Given PO

Other:
• Placebo
Given transdermally
• Laboratory Biomarker Analysis
Correlative studies
• Questionnaire Administration
Ancillary studies

Locations

Country	Name	City	State
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

Sponsors (2)

Lead Sponsor	Collaborator
Northwestern University	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Plasma Concentrations of Telapristone Acetate	Post-therapy plasma concentrations of telapristone acetate.	At the time of mastectomy, up to 5 weeks from baseline
Secondary	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
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.	Baseline to mastectomy (up to 5 weeks)
Secondary	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
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	Baseline to mastectomy (up to 5 weeks)
Secondary	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)
Secondary	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)