Clinical Trials /

Transdermal or Oral Telapristone Acetate in Treating Patients Undergoing Mastectomy

NCT02314156

Description:

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.

Related Conditions:
  • Breast Carcinoma
  • Hereditary Breast and Ovarian Cancer Syndrome
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Transdermal or Oral <span class="go-doc-concept go-doc-intervention">Telapristone Acetate</span> in Treating Patients Undergoing Mastectomy

Title

  • Brief Title: Transdermal or Oral Telapristone Acetate in Treating Patients Undergoing Mastectomy
  • Official Title: Intra-mammary Distribution of Transdermal Telapristone Versus Oral Telapristone: A Randomized Window Trial in Women Undergoing Mastectomy
  • Clinical Trial IDs

    NCT ID: NCT02314156

    ORG ID: NCI 2013-01-03

    NCI ID: NCI-2014-02412

    Trial Conditions

    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

    Trial Interventions

    Drug Synonyms Arms
    Telapristone Acetate CDB-4124, Proellex, Progenta Arm I (transdermal telapristone acetate)
    Telapristone Acetate CDB-4124, Proellex, Progenta Arm II (oral telapristone acetate)

    Trial Purpose

    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 [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 (ER) and TUNEL using immunohistochemistry (IHC) at baseline and
    after treatment.

    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.

    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.

    Trial Arms

    Name Type Description Interventions
    Arm I (transdermal telapristone acetate) Experimental Patients receive telapristone acetate transdermally and placebo PO QD for 4 weeks. Telapristone Acetate
    Arm II (oral telapristone acetate) Active Comparator Patients receive placebo transdermally and telapristone acetate PO QD for 4 weeks. Telapristone Acetate

    Eligibility 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)

    - 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

    - 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:

    - The presence of skin invasion by the breast cancer, or inflammatory changes with skin
    edema AND erythema

    - Women with skin diseases (psoriasis, eczema)

    - 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

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Female

    Primary Outcome Measures

    Mean levels of telapristone acetate in breast tissue

    Secondary Outcome Measures

    Plasma concentrations of telapristone acetate

    Within-breast variation of breast tissue concentration of telapristone acetate

    Changes in cell proliferation and apoptosis

    Changes in gene expression

    Change in serum progesterone

    Incidence of adverse events, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

    Trial Keywords