Invasive Breast CancerEarly Phase 1NCT01138553
Preoperative Testing of the Anti-Progesterone Mifepristone in Early Stage Breast Cancer
A Early Phase 1 study testing Mifepristone in people with Invasive Breast Cancer and Ductal Carcinoma in Situ, run by University of California, San Diego at 1 site in United States.
Trial summary
The primary objective of this study is to identify the group of women with early stage breast cancer most likely to benefit from treatment with the selective progesterone receptor modulator (SPRM) mifepristone. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Invasive Breast Cancer, Ductal Carcinoma in Situ
- What is being tested?
- Mifepristone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2010to Oct 2015
- Phase
- Early 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 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female identified as a candidate for primary resection of breast cancer (invasive or ductal carcinoma in situ) by a UCSD Breast Care Unit surgical oncologist
- Subjects must agree to contact the study coordinator prior to starting any new medications, vitamins or herbals during, or for 2 weeks following, mifepristone use
- Subjects must agree to abstain from alcohol use while on mifepristone
- Age ≥18
- ECOG performance status 0-1
- Prior to starting mifepristone subjects must have a negative urine (βHCG combo with on-board control) or blood pregnancy test and must be using one of the following acceptable means of birth control prior to starting study drug; Barrier methods or surgically sterile (tubal ligation, hysterectomy or partner with confirmed vasectomy). Alternatively the subject must be one year post-menopausal defined as greater than 12 months without a menstrual cycle
- Prior to starting mifepristone subjects must meet the following laboratory criteria; Granulocytes > 1.5E9/l (grade ≤ 1); Platelets ≥ 100E9/l; Hemoglobin > 10 g/dl (grade ≤ 1); Creatinine < 1.5x normal reference range (grade ≤ 1); SGOT, SGPT, alk phos ≤ 1x normal reference range; Total bilirubin < 1x normal reference range; Calcium < 11.5 mg/dl (grade ≤ 1); HBsAg = Negative; HCV Ab = Negative; INR < 1.5;
- Subjects must provide written informed consent
Who cannot join
- Not scheduled for surgery within 5 days of enrollment
- Subjects must not be on any therapy to treat breast cancer prior to surgical resection, specifically medications or recent (within 1 month of diagnostic biopsy) withdrawal of estrogen containing medication (eg. hormone replacement therapy)
- Subjects must not be on any medications, vitamins or herbals that are; potent inhibitors of cytochrome P450 CYP3A4, or sensitive substrates for cytochrome P450 CYP3A4
- Subjects may not have any history of significant cardiovascular, renal or hepatic disease requiring ongoing medical therapy or clinical intervention
- Subjects may not have a history of thrombophlebitis, thromboembolic disorder, or cerebral vascular disease.
- Subjects may not have any known hypersensitivity to mifepristone
- Subjects may not have a BMI > 39
- Subjects may not have an IUD (Intrauterine contraceptive device), chronic adrenal failure, concurrent long term steroid therapy, history of allergy to mifepristone, hemorrhagic disorders or concurrent anticoagulant therapy, or inherited porphyrias
Trial locations and contacts
1 site in 1 country.
United States1 site
Moores UCSD Cancer Center
La Jolla, California, 92093
About this study
Official title: A Biomarker Study of Mifepristone in Early Stage Breast Cancer
The primary objective of this study is to identify the group of women with early stage breast cancer most likely to benefit from treatment with the selective progesterone receptor modulator (SPRM) mifepristone. This will be done by treating women briefly prior to planned surgery and examining the decrease in growth rate (measured by Ki-67 immunohistochemistry) in tumor samples taken before and after exposure to mifepristone.
Read the detailed description
Secondary objectives of this study include; (1) Measuring objective response in tumor size with treatment, (2) Establishing the safety and tolerability of short term mifepristone exposure in early stage breast cancer patients, and (3) Performing exploratory studies of expression of related targets following drug exposure.
Anti-estrogen therapy has been a mainstay of breast cancer treatment for over three decades. It is highly effective and has modest toxicity, certainly in comparison to chemotherapy. The selective estrogen receptor modulator tamoxifen has the longest history but a number of aromatase inhibitors and the anti-estrogen fulvestrant are also in widespread use along with ovarian ablation for pre-menopausal women. Given the success of this approach, and the highly analogous parallel progesterone signal, it is unfortunate that anti-progesterone therapy has not been similarly pursued. Additionally, data from the Woman's Health Initiative trial reveal a potentially significant role for progesterone in breast cancer development and growth. Healthy postmenopausal women treated with the combination of estrogen and progesterone over a 5 year period were 24% more likely to develop invasive breast cancer and had larger tumors at diagnosis. Notably this effect was not seen in post-hysterectomy women treated with estrogen alone over nearly 7 years. In fact a non-statistically significant reduction in breast cancer incidence was observed with estrogen alone.
The anti-progesterone mifepristone has been found to reduce proliferation in normal breast tissue. Even a low dose of mifepristone (50mg every other day for 3 months) demonstrated a statistically significant reduction in breast cell proliferation (measured by Ki-67 immunohistochemistry).
Higher doses of mifepristone, 200mg daily, have been used in patients with metastatic breast cancer for durations of almost 2 years without serious toxicity. Response rates were only 11% but no grade 4 or 5 toxicities occurred. Some grade 3 toxicities occurred, including lethargy, nausea, vomiting, and skin rash. These rashes resolved with temporary discontinuation of drug and did not recur when drug was resumed.
As a whole these data strongly support research into anti-progesterone therapy for early stage breast cancer. To our knowledge this is the first such study.
- Conditions
- Invasive Breast Cancer, Ductal Carcinoma in Situ
- Being tested
- Mifepristone
- Keywords
- biomarker, breast cancer, antiprogesterone
- Medical subject headings
- Carcinoma, Intraductal, Noninfiltrating, Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MifepristoneDrug
200mg capsules daily for 5-28 days
| Study group | Role | What they receive |
|---|---|---|
| Mifepristone | Experimental | Not described Receives: Drug: Mifepristone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in proliferation by Ki-67 immunohistochemistry.
Measured: 5-30 days
Secondary outcomes (2)
Tumor size
Measured: 5-30 days
Expression of related targets following mifepristone exposure
RNA-seq will be used to evaluate expression of steroid receptor isoform expression following drug exposure. These data will be compared with response as measured by proliferation change and tumor size.
Measured: 5-28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2010 (estimated)
- Study startJun 2010
- Primary completionJun 2014
- Study completionOct 2015
Why it stopped: Inadequate subject accrual
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 Invasive Breast CancerStudies of the same condition, open and under way.
- More trials run by University of California, San DiegoThe 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Richard Schwab, University of California, San Diego
- Investigators
- Richard B Schwab, MD, Principal investigator, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01138553
- Sponsor's protocol ID
- UCSD#100231
- Status last verified
- Jul 2019
- First submitted
- 4 Jun 2010
- Last updated
- 8 Jul 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Chlebowski RT, Hendrix SL, Langer RD, Stefanick ML, Gass M, Lane D, Rodabough RJ, Gilligan MA, Cyr MG, Thomson CA, Khandekar J, Petrovitch H, McTiernan A; WHI Investigators. Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women's Health Initiative Randomized Trial. JAMA. 2003 Jun 25;289(24):3243-53. doi: 10.1001/jama.289.24.3243.
PubMed 12824205
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Biomarker Study of Mifepristone in Early Stage Breast Cancer
- ClinicalTrials.gov ID
- NCT01138553
- Acronym / sponsor ID
- UCSD#100231
- Conditions
- Invasive Breast Cancer, Ductal Carcinoma in Situ
- Keywords
- biomarker, breast cancer, antiprogesterone
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Inadequate subject accrual
- Enrolment
- 4 participants (actual)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Study start
- Jun 2010 (actual)
- Primary completion
- Jun 2014 (actual)
- Study completion
- Oct 2015 (actual)
- First posted
- 7 Jun 2010 (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.
The primary objective of this study is to identify the group of women with early stage breast cancer most likely to benefit from treatment with the selective progesterone receptor modulator (SPRM) mifepristone. This will be done by treating women briefly prior to planned surgery and examining the decrease in growth rate (measured by Ki-67 immunohistochemistry) in tumor samples taken before and after exposure to mifepristone.
Detailed description
Secondary objectives of this study include; (1) Measuring objective response in tumor size with treatment, (2) Establishing the safety and tolerability of short term mifepristone exposure in early stage breast cancer patients, and (3) Performing exploratory studies of expression of related targets following drug exposure.
Anti-estrogen therapy has been a mainstay of breast cancer treatment for over three decades. It is highly effective and has modest toxicity, certainly in comparison to chemotherapy. The selective estrogen receptor modulator tamoxifen has the longest history but a number of aromatase inhibitors and the anti-estrogen fulvestrant are also in widespread use along with ovarian ablation for pre-menopausal women. Given the success of this approach, and the highly analogous parallel progesterone signal, it is unfortunate that anti-progesterone therapy has not been similarly pursued. Additionally, data from the Woman's Health Initiative trial reveal a potentially significant role for progesterone in breast cancer development and growth. Healthy postmenopausal women treated with the combination of estrogen and progesterone over a 5 year period were 24% more likely to develop invasive breast cancer and had larger tumors at diagnosis. Notably this effect was not seen in post-hysterectomy women treated with estrogen alone over nearly 7 years. In fact a non-statistically significant reduction in breast cancer incidence was observed with estrogen alone.
The anti-progesterone mifepristone has been found to reduce proliferation in normal breast tissue. Even a low dose of mifepristone (50mg every other day for 3 months) demonstrated a statistically significant reduction in breast cell proliferation (measured by Ki-67 immunohistochemistry).
Higher doses of mifepristone, 200mg daily, have been used in patients with metastatic breast cancer for durations of almost 2 years without serious toxicity. Response rates were only 11% but no grade 4 or 5 toxicities occurred. Some grade 3 toxicities occurred, including lethargy, nausea, vomiting, and skin rash. These rashes resolved with temporary discontinuation of drug and did not recur when drug was resumed.
As a whole these data strongly support research into anti-progesterone therapy for early stage breast cancer. To our knowledge this is the first such study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Mifepristone | Experimental | Drug: Mifepristone |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Female identified as a candidate for primary resection of breast cancer (invasive or ductal carcinoma in situ) by a UCSD Breast Care Unit surgical oncologist
- Subjects must agree to contact the study coordinator prior to starting any new medications, vitamins or herbals during, or for 2 weeks following, mifepristone use
- Subjects must agree to abstain from alcohol use while on mifepristone
- Age ≥18
- ECOG performance status 0-1
Key exclusion criteria (8 listed)
- Not scheduled for surgery within 5 days of enrollment
- Subjects must not be on any therapy to treat breast cancer prior to surgical resection, specifically medications or recent (within 1 month of diagnostic biopsy) withdrawal of estrogen containing medication (eg. hormone replacement therapy)
- Subjects must not be on any medications, vitamins or herbals that are; potent inhibitors of cytochrome P450 CYP3A4, or sensitive substrates for cytochrome P450 CYP3A4
- Subjects may not have any history of significant cardiovascular, renal or hepatic disease requiring ongoing medical therapy or clinical intervention
- Subjects may not have a history of thrombophlebitis, thromboembolic disorder, or cerebral vascular disease.
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 |
|---|---|---|
| Mifepristone200mg capsules daily for 5-28 days | Drug | Mifepristone |
Primary outcome
Change in proliferation by Ki-67 immunohistochemistry.
Time frame: 5-30 days
2 secondary outcomes
Tumor size
Time frame: 5-30 days
Expression of related targets following mifepristone exposure
Time frame: 5-28 days
Results and safety
The study was stopped early (reason given: Inadequate subject accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2019.
- Background: PubMed 12824205Chlebowski RT, Hendrix SL, Langer RD, Stefanick ML, Gass M, Lane D, Rodabough RJ, Gilligan MA, Cyr MG, Thomson CA, Khandekar J, Petrovitch H, McTiernan A; WHI Investigators. Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women's Health Initiative Randomized Trial. JAMA. 2003 Jun 25;289(24):3243-53. doi: 10.1001/jama.289.24.3243.
- UCSD Moores Cancer Center Clinical TrialsLink provided by the sponsor.
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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.
Richard B Schwab, MD principal investigator
University of California, San Diego
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Mifepristone in people with Invasive Breast Cancer and Ductal Carcinoma in Situ, run by University of California, San Diego at 1 site 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 8 inclusion and 8 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: stopped early, as of the sponsor's last update on 8 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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 was stopped early (reason given: Inadequate subject accrual). Results are not available in the source record.
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 proliferation by Ki-67 immunohistochemistry. (time frame: 5-30 days). 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 NCT01138553, 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 8 Jul 2019.