NCT02922127

Brief Summary

Breast cancer accounts for almost a quarter of all cancers in women. In the United States (U.S.) in 2014, more than 230,000 women were diagnosed and 40,000 died of breast cancer. There is an urgent need to develop acceptable means of preventing breast cancer both for high risk and average risk women. The proposed study is a clinical trial in premenopausal women aged 18-39 to evaluate the capacity of daily Ulipristal Acetate (UPA) to reduce breast epithelial cell proliferation (increase in number of cells in the breast) and to measure its effect compared to that found with a combined estrogen-progestin oral contraceptive (COC). UPA is an anti-progestin in use as daily medication up to 12 months for the treatment of abnormally heavy bleeding at menstruation due to uterine fibroids, and is currently in trials in the U.S. to evaluate its use as a daily contraceptive. The investigators will use breast biopsies to compare breast cell proliferation, comparing biopsies at the end of 3 months treatment to biopsies taken at baseline in the 2 groups (UPA and COC). The investigators will also compare the changes in the 2 groups to each other. The comparison of the effect of UPA to that of a conventional COC is because of UPA's potential use as a daily contraceptive. Cell proliferation in the breast occurs throughout the menstrual cycle. The actions of hormones on the breast are rapid and an anti-progestin such as UPA, which will block the action of progesterone in the breast, would be predicted to quickly lower breast cell proliferation in premenopausal women. Effects of UPA on the uterus continue to be studied and are reassuring. COC use has not been found to lower breast cell proliferation and is not associated with any decrease in risk of breast cancer. The changes in breast cell proliferation will also be compared to changes seen on breast MRI. If the changes are highly correlated future studies will be able to be done without the need for breast biopsies.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
29

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Dec 2016

Typical duration for phase_1

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 25, 2016

Completed
2 months until next milestone

First Posted

Study publicly available on registry

October 4, 2016

Completed
2 months until next milestone

Study Start

First participant enrolled

December 16, 2016

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 21, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 21, 2019

Completed
Last Updated

February 7, 2020

Status Verified

February 1, 2020

Enrollment Period

2.8 years

First QC Date

July 25, 2016

Last Update Submit

February 5, 2020

Conditions

Contraception

Keywords

Ulipristal Acetate (UPA)Breast CancerCombined Oral Contraceptive (COC)

Outcome Measures

Primary Outcomes (1)

  • Change in breast epithelial cell proliferation rate

    The breast biopsies will be analyzed (measured by Ki67) at end of study treatment, as compared with baseline before initiation of treatment.

    Baseline, three months

Secondary Outcomes (3)

  • Change in breast epithelial cell proliferation rate in the UPA group compared to the change in the COC group

    Three months

  • Proportion of subjects using UPA who experience a categorical decrease in breast background parenchymal enhancement (BPE)

    Baseline, three months

  • Proportion of subjects experiencing a categorical decrease in breast BPE in the UPA group compared to the change in the COC group

    Three months

Study Arms (2)

Ulipristal Acetate

OTHER

20 women will randomized to daily use of 10mg of ulipristal acetate

Drug: Ulipristal Acetate

Combined Oral Contraceptive

OTHER

20 women will be randomized to daily use of a combined oral contraceptive pill

Drug: Combined Oral Contraceptive Pill

Interventions

Ulipristal AcetateDRUG

Daily use of Ulipristal Acetate

Also known as: Ella
Ulipristal Acetate
Combined Oral Contraceptive PillDRUG

Daily use of Oral Contraceptive Pill

Also known as: Portia
Combined Oral Contraceptive

Eligibility Criteria

Age18 Years - 39 Years
Sexfemale
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Women between 18 and 39 years of age (inclusive).
  • In good health, with regular menstrual cycles between 21 and 35 days and with intra-individual variation of less than or equal to 5 days.
  • Volunteers who are postpartum or who aborted in the first or second trimester must have had two normal menstrual cycles (3 bleeding episodes) prior to screening.
  • No use of any other hormonal contraception within two normal menstrual cycles (3 bleeding episodes) prior to screening.
  • If previous use of injectable Depo Provera, subject must have had two normal menstrual cycles (3 bleeding episodes) prior to screening.
  • Not at risk for pregnancy:
  • Using a copper intra uterine device (IUD), or
  • Willing to protect all further acts of intercourse with condoms, or
  • Not hetero-sexually active, or
  • Having undergone previous tubal ligation, or
  • Partner sterilized or vasectomized.
  • Body Mass Index (BMI) \< 30 kg/m2 and not having previously undergone bariatric surgery.
  • Diastolic blood pressure (BP) ≤ 90 mm Hg and systolic BP ≤ 140 mm Hg after at least 5 minutes in a sitting position. Hypertensive subjects who are treatment controlled may obtain a waiver for participation.
  • Willing and able to follow all study requirements, including use of the study medication and willing to give information related to study medication use as required during the study, in the opinion of the investigator.
  • Able to give informed consent to participate in the study.

You may not qualify if:

  • Currently pregnant as confirmed by positive high-sensitivity urine pregnancy test.
  • Currently breast-feeding or within 30 days of discontinuing breast feeding at screening.
  • Undiagnosed abnormal genital bleeding.
  • Known hypersensitivity to an active substance or any of the excipients of the study treatments.
  • Abnormal clinical breast examination at screening.
  • Suspected hyperplasia or carcinoma of the endometrium.
  • Ovarian cyst \> 25 mm observed on transvaginal or transabdominal ultrasound performed on the first visit of the Baseline cycle.
  • History of any diagnostic or therapeutic breast biopsy
  • Any of the known contraindications to COC use:
  • History of or existing breast cancer, or other hormone sensitive neoplasia, or
  • History of or current ischemic heart disease or stroke, or
  • History of or current deep venous thrombosis or pulmonary embolism, or
  • Systemic lupus erythematosus with positive or unknown antiphospholipid antibodies, or
  • History of or current benign or malignant liver tumor, or
  • Severe (decompensated) cirrhosis.
  • +5 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

Weill Cornell Medical Center

New York, New York, 10065, United States

Location

Related Publications (1)

  • Westhoff CL, Guo H, Wang Z, Hibshoosh H, Polaneczky M, Pike MC, Ha R. The progesterone-receptor modulator, ulipristal acetate, drastically lowers breast cell proliferation. Breast Cancer Res Treat. 2022 Apr;192(2):321-329. doi: 10.1007/s10549-021-06503-1. Epub 2022 Jan 11.

    PMID: 35015210DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

ulipristal acetateContraceptives, Oral, CombinedEthinyl Estradiol-Norgestrel Combination

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Drug CombinationsPharmaceutical PreparationsContraceptives, OralContraceptive Agents, FemaleContraceptive AgentsReproductive Control AgentsPhysiological Effects of DrugsPharmacologic ActionsChemical Actions and UsesTherapeutic UsesEthinyl EstradiolNorpregnatrienesNorpregnanesNorsteroidsSteroidsFused-Ring CompoundsPolycyclic CompoundsNorgestrelNorpregnenesEstrogenic Steroids, AlkylatedEstradiol CongenersGonadal Steroid HormonesGonadal HormonesHormonesHormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

  • Carolyn Westhoff, MD

    Columbia University

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor, Department of Obstetrics and Gynecology

Study Record Dates

First Submitted

July 25, 2016

First Posted

October 4, 2016

Study Start

December 16, 2016

Primary Completion

October 21, 2019

Study Completion

October 21, 2019

Last Updated

February 7, 2020

Record last verified: 2020-02

Locations

US(2)