ContraceptionPhase 1NCT02922127
Compare Daily Ulipristal Acetate and Combined Oral Contraceptive Effects on Breast Epithelial Cell Proliferation
A Phase 1 study testing Ulipristal Acetate and Combined Oral Contraceptive Pill in people with Contraception, run by Columbia University at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 39 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Contraception
- What is being tested?
- Ulipristal Acetate and Combined Oral Contraceptive Pill
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 2 sitesUnited States
- Study dates
- 16 Dec 2016to 21 Oct 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 39 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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:
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- 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.
Who cannot join
- 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.
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- 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.
- Headaches with focal neurological symptoms.
- Hereditary galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.
- Known or suspected alcoholism or drug abuse.
- Known human immunodeficiency virus (HIV) infection.
- Smoking 15 cigarettes or more per day, if in the opinion of the investigator or medically qualified designee, this would increase the risk for cardiovascular disease and thromboembolism based on risk factors.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Columbia University Irving Medical Center
New York, New York, 10032
Weill Cornell Medical Center
New York, New York, 10065
About this study
Official title: A Prospective, Randomized, Single-blind Study to Compare the Effects of Daily Ulipristal Acetate (UPA) 10mg With a Combined Oral Contraceptive (COC) Pill on Breast Epithelial Cell Proliferation in Reproductive Age Women
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.
Read more
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.
Read the detailed description
This will be a randomized controlled parallel group clinical trial with blinded evaluation to be carried out at 2 academic medical centers: Columbia University Medical Center and Weill Cornell Medical College. The investigators will screen healthy women aged 18-39 who meet inclusion/exclusion criteria and will enroll them for the study.
After the informed consent process and study enrollment, study participation will begin with a baseline cycle. The main goal of the baseline cycle is to identify the occurrence and the timing of ovulation. Starting at about day 6 of the baseline cycle, participants will undergo blood sampling for progesterone (P4) levels at intervals of every 2-3 days. An increase of P4 to greater than 3 ng/mL, confirmed by a second such value, will indicate ovulation and eligibility to continue in the study. The participant's baseline breast MRI and biopsy (see below) will be scheduled to occur in the mid luteal phase, about 7 days after the first increase (>3 ng/mL) in P4. The investigators will randomly assign which breast has the first biopsy, and women will return for a post-biopsy visit about 7 days later. At the post-biopsy visit, the investigators will assess acceptability of the MRI and biopsy to the participants using visual analog scales (VAS) as well as interview.
At the beginning of the next menstrual period, women will begin the treatment phase of the study. They will receive random assignment to either UPA or COC at the study center and receive their first dose and a 4-week supply of study drug. During cycles 1 and 2 they will return to the study site every 2 weeks for assessment, blood draws and to receive the next cycle of study drug. During the third cycle, they will return to the study site twice weekly for more frequent testing and monitoring. Each cycle will be 28 days, corresponding to usual COC packaging. At day 75-77 of treatment women will undergo the second breast MRI, immediately followed by a biopsy of the contralateral breast to that biopsied at baseline. An end-of-study visit, including checking the incision site and a repeat assessment of acceptability of the MRI and biopsy to the participants, will occur about 7 days later. Participants will also be asked to rate their preference for an MRI versus a biopsy, were it possible to do a study with only one of these procedures.
Participants will have up to 24 study visits, and at each visit, participants will be asked about adverse events and use of any concomitant medications. Participants will have a high sensitivity urine pregnancy test at baseline and immediately preceding each MRI and preceding the first dose of study medication. Any participant with a positive pregnancy test will be immediately withdrawn from the study.
Breast Biopsies Breast biopsies will take place immediately following each breast MRI. Women will receive 24-hour telephone follow-up, and make a visit within one week following each breast biopsy to ensure that the biopsy site is healing without incident.
MRI For each participant, the baseline and follow-up MRI will be done using the same machine. Each MRI study will undergo an immediate wet read to assure adequate quality and to identify any unexpected pathology that would mandate clinical evaluation and withdrawal from the study. A limited report indicating technical adequacy and absence of major clinical abnormalities will be recorded in the patient record.
Breast MRI and breast biopsy visits will take place at the Center for Breast Imaging at Columbia University Medical Center.
- Conditions
- Contraception
- Being tested
- Ulipristal Acetate, Combined Oral Contraceptive Pill
- Keywords
- Ulipristal Acetate (UPA), Breast Cancer, Combined Oral Contraceptive (COC)
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ulipristal AcetateDrug
Also called Ella
Daily use of Ulipristal Acetate
Combined Oral Contraceptive PillDrug
Also called Portia
Daily use of Oral Contraceptive Pill
| Study group | Role | What they receive |
|---|---|---|
| Ulipristal Acetate | Other | 20 women will randomized to daily use of 10mg of ulipristal acetate Receives: Drug: Ulipristal Acetate |
| Combined Oral Contraceptive | Other | 20 women will be randomized to daily use of a combined oral contraceptive pill Receives: Drug: Combined Oral Contraceptive Pill |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
The breast biopsies will be analyzed (measured by Ki67).
Measured: Three months
Proportion of subjects using UPA who experience a categorical decrease in breast background parenchymal enhancement (BPE)
This will be measured with contrast MRI.
Measured: 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
This will be measured with contrast MRI.
Measured: Three months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2016 (estimated)
- Study start16 Dec 2016
- Primary completion21 Oct 2019
- Study completion21 Oct 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ContraceptionStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Collaborators
- Weill Medical College of Cornell University, Memorial Sloan Kettering Cancer Center
- Responsible party
- Principal investigator, Carolyn Westhoff, Columbia University
- Investigators
- Carolyn Westhoff, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02922127
- Sponsor's protocol ID
- AAAQ8498
- Status last verified
- Feb 2020
- First submitted
- 25 Jul 2016
- Last updated
- 7 Feb 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 35015210
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Randomized, Single-blind Study to Compare the Effects of Daily Ulipristal Acetate (UPA) 10mg With a Combined Oral Contraceptive (COC) Pill on Breast Epithelial Cell Proliferation in Reproductive Age Women
- ClinicalTrials.gov ID
- NCT02922127
- Acronym / sponsor ID
- AAAQ8498
- Conditions
- Contraception
- Keywords
- Ulipristal Acetate (UPA), Breast Cancer, Combined Oral Contraceptive (COC)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Collaborators
- Weill Medical College of Cornell University, Memorial Sloan Kettering Cancer Center
- Study start
- 16 Dec 2016 (actual)
- Primary completion
- 21 Oct 2019 (actual)
- Study completion
- 21 Oct 2019 (actual)
- First posted
- 4 Oct 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This will be a randomized controlled parallel group clinical trial with blinded evaluation to be carried out at 2 academic medical centers: Columbia University Medical Center and Weill Cornell Medical College. The investigators will screen healthy women aged 18-39 who meet inclusion/exclusion criteria and will enroll them for the study.
After the informed consent process and study enrollment, study participation will begin with a baseline cycle. The main goal of the baseline cycle is to identify the occurrence and the timing of ovulation. Starting at about day 6 of the baseline cycle, participants will undergo blood sampling for progesterone (P4) levels at intervals of every 2-3 days. An increase of P4 to greater than 3 ng/mL, confirmed by a second such value, will indicate ovulation and eligibility to continue in the study. The participant's baseline breast MRI and biopsy (see below) will be scheduled to occur in the mid luteal phase, about 7 days after the first increase (>3 ng/mL) in P4. The investigators will randomly assign which breast has the first biopsy, and women will return for a post-biopsy visit about 7 days later. At the post-biopsy visit, the investigators will assess acceptability of the MRI and biopsy to the participants using visual analog scales (VAS) as well as interview.
At the beginning of the next menstrual period, women will begin the treatment phase of the study. They will receive random assignment to either UPA or COC at the study center and receive their first dose and a 4-week supply of study drug. During cycles 1 and 2 they will return to the study site every 2 weeks for assessment, blood draws and to receive the next cycle of study drug. During the third cycle, they will return to the study site twice weekly for more frequent testing and monitoring. Each cycle will be 28 days, corresponding to usual COC packaging. At day 75-77 of treatment women will undergo the second breast MRI, immediately followed by a biopsy of the contralateral breast to that biopsied at baseline. An end-of-study visit, including checking the incision site and a repeat assessment of acceptability of the MRI and biopsy to the participants, will occur about 7 days later. Participants will also be asked to rate their preference for an MRI versus a biopsy, were it possible to do a study with only one of these procedures.
Participants will have up to 24 study visits, and at each visit, participants will be asked about adverse events and use of any concomitant medications. Participants will have a high sensitivity urine pregnancy test at baseline and immediately preceding each MRI and preceding the first dose of study medication. Any participant with a positive pregnancy test will be immediately withdrawn from the study.
Breast Biopsies Breast biopsies will take place immediately following each breast MRI. Women will receive 24-hour telephone follow-up, and make a visit within one week following each breast biopsy to ensure that the biopsy site is healing without incident.
MRI For each participant, the baseline and follow-up MRI will be done using the same machine. Each MRI study will undergo an immediate wet read to assure adequate quality and to identify any unexpected pathology that would mandate clinical evaluation and withdrawal from the study. A limited report indicating technical adequacy and absence of major clinical abnormalities will be recorded in the patient record.
Breast MRI and breast biopsy visits will take place at the Center for Breast Imaging at Columbia University Medical Center.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ulipristal Acetate | Other | Drug: Ulipristal Acetate20 women will randomized to daily use of 10mg of ulipristal acetate |
| Combined Oral Contraceptive | Other | Drug: Combined Oral Contraceptive Pill20 women will be randomized to daily use of a combined oral contraceptive pill |
Who may qualify
- Ages
- 18 to 39 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (15 listed)
- 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.
Key exclusion criteria (20 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ulipristal AcetateAlso: EllaDaily use of Ulipristal Acetate | Drug | Ulipristal Acetate |
| Combined Oral Contraceptive PillAlso: PortiaDaily use of Oral Contraceptive Pill | Drug | Combined Oral Contraceptive |
Primary outcome
Change in breast epithelial cell proliferation rate
Time frame: Baseline, three months
The breast biopsies will be analyzed (measured by Ki67) at end of study treatment, as compared with baseline before initiation of treatment.
3 secondary outcomes
Change in breast epithelial cell proliferation rate in the UPA group compared to the change in the COC group
Time frame: Three months
Proportion of subjects using UPA who experience a categorical decrease in breast background parenchymal enhancement (BPE)
Time frame: 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
Time frame: Three months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2020.
- Derived from this study: PubMed 35015210Westhoff 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Carolyn Westhoff, MD principal investigator
Columbia University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ulipristal Acetate and Combined Oral Contraceptive Pill in people with Contraception, run by Columbia University at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in breast epithelial cell proliferation rate (time frame: Baseline, three months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02922127, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Feb 2020.