Breast CancerPhase 2NCT00853996
Acolbifene in Preventing Cancer in Premenopausal Women at High Risk of Breast Cancer
A Phase 2 study testing acolbifene hydrochloride in people with Breast Cancer, run by University of Kansas Medical Center at 1 site in United States.
Trial summary
This phase II trial is studying how well acolbifene works in preventing cancer in premenopausal women at high risk of breast cancer. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of acolbifene may stop cancer from growing or coming back. Read more about this study
- Who is it for?
- Ages 30 to 55 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Breast Cancer
- What is being tested?
- acolbifene hydrochloride
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2009to Dec 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 30 to 55 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Gail risk >= 1.7% and/or relative risk >= 3 times that for 5-year age group
- Premenopausal
- More than 6 months since initiating or discontinuing oral contraceptives
- At increased risk for breast cancer, as indicated by >= 1 of the following risk factors:
- BRCA1/2 mutation characterized as deleterious or of uncertain significance
- Prior atypical ductal hyperplasia, ductal carcinoma in situ, or lobular carcinoma in situ
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- Prior random periareolar fine needle aspiration (RPFNA) showing atypical hyperplasia
- Family history consistent with hereditary breast cancer, as indicated by 1 of the following criteria:
- >= 4 relatives with breast cancer
- >= 2 relatives diagnosed with breast cancer at ≤ 50 years of age
- Breast and ovarian cancer diagnosed in same relative
- No suspicion for breast cancer on baseline mammogram performed between days 1-10 of menstrual cycle within 3 months prior to screening baseline RPFNA
- Exhibits hyperplasia with or without atypia (Masood score >= 14) with >= 500 cells AND Ki-67 positivity >= 2% by RPFNA performed within 6 months prior to initiation of study drug
- Estimated visual mammographic breast density category >= 5% on mammogram performed within 6 months prior to initiation of study drug
- Has regular menstrual cycles (between 21 and 35 days) unless using extended regimen oral contraceptives or a contraceptive device (e.g., Mirena IUD) Values for metabolic profile and blood count within normal limits
- Absolute granulocyte count > 1,000/mm^3
- Platelets > 100,000/mm^3
- Hemoglobin > 10 g/dL
- Bilirubin < 2.0 mg/dL
- AST < 2 times upper limit of normal (ULN)
- Albumin > 3.0 g/dL
- Creatinine < 1.5 mg/dL
- Alkaline phosphatase < 2 times ULN
- Concurrent hormonal contraceptives allowed provided patient remains on the same hormonal regimen from 3 months prior to baseline aspiration until the completion of study treatment
- Fertile patients must use effective contraception during and for 3 months after completion of study treatment
- Willing to ingest recommended dose of calcium and vitamin D for premenopausal bone health (1,200 mg calcium and 800 IU vitamin D daily)
- Negative pregnancy test prior to receiving study agent
Who cannot join
- pregnant or nursing
- nursing within the past 6 months
- Known osteoporosis or severe osteopenia (T-score -2 or worse by DEXA)
- History of symptomatic endometriosis with pelvic pain, poorly controlled migraines, or hot flashes
- History of deep venous thrombosis
- History of allergic reactions attributed to compounds of similar chemical or biological composition to the study agent
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- Other condition or concurrent illness that, in the opinion of the investigator, would make the patient a poor candidate for RPFNA
- Less than 1 year since prior use of aromatase inhibitors (e.g., anastrozole, exemestane, or letrozole) or selective estrogen receptor modulators (e.g., tamoxifen citrate, raloxifene, or arzoxifene hydrochloride)
- Other concurrent chemopreventive agents
- Concurrent anticoagulants
- Other concurrent investigational agents
- Bilateral breast implants
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Kansas Medical Center
Kansas City, Kansas, 66160
About this study
Official title: Phase II Study of Acolbifene in Pre-Menopausal Women at High Risk for Breast Cancer
This phase II trial is studying how well acolbifene works in preventing cancer in premenopausal women at high risk of breast cancer. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of acolbifene may stop cancer from growing or coming back.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the effect of six months of acolbifene 20 mg/day on Ki-67 in high risk premenopausal women with baseline hyperplasia +/- atypia and Ki-67 positivity of >= 2%..
SECONDARY OBJECTIVES:
- To determine the effect of six months of acolbifene 20 mg/day on mammographic breast density in high risk premenopausal women.
II. To determine the effect of six months of acolbifene 20 mg/day on serum levels of follicular phase bioavailable estradiol, and luteal phase progesterone, testosterone, and fasting IGF-1/IGFBP-3.
III. To determine the effect of six months of acolbifene 20 mg/day on epithelial cell cytomorphology and molecular markers such as ER, PgR, and pS2.
IV. To determine the effect of six months of acolbifene on markers of cardiovascular risk (C-reactive protein, functional AntiThrombin III, and fasting lipid profile) and bone turnover markers associated with bone mineral density gain or loss (serum osteocalcin and N-telopeptide crosslinks).
- To assess any increase in reported hot flashes, menstrual cycle irregularities, pelvic pain, musculoskeletal complaints, and fatigue from baseline.
OUTLINE:
Patients receive oral acolbifene hydrochloride once daily for 6 months in the absence of unacceptable toxicity.
Patients undergo symptom assessment (hot flashes, menstrual abnormalities, pelvic pain, muscle and joint pain, and fatigue) at baseline, 6-8 weeks, monthly for 6 months, and then at 2 weeks after completion of study treatment.
Patients undergo random periareolar fine needle aspiration between days 1-10 of menstrual cycle at baseline and at 6 months. Patients also undergo blood sample collection between days 1-10 and days 20-24 of menstrual cycle at baseline and at 6 months. Samples taken between days 1-10 of menstrual cycle are analyzed for Ki-67 expression, cytomorphology, molecular markers (estrogen receptor, progesterone receptor, and pS2 expression), and bioavailable estradiol levels. Samples taken between days 20-24 of menstrual cycle are analyzed for progesterone, testosterone, IGF-1, IGFBP-3, lipid profile, bone-turnover markers (osteocalcin and N-telopeptide crosslinks), C-reactive protein, and functional antithrombin III.
After completion of study treatment, patients are followed at 2 weeks.
- Conditions
- Breast Cancer
- Being tested
- acolbifene hydrochloride
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
acolbifene hydrochlorideDrug
Also called EM-652.HCL, SCH 57068.HCl
Given orally
| Study group | Role | What they receive |
|---|---|---|
| Prevention (acolbifene hydrochloride) | Experimental | Patients receive oral acolbifene hydrochloride once daily for 6 months in the absence of unacceptable toxicity. Receives: Drug: acolbifene hydrochloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in the Percentage of Breast Epithelial Cells Expressing Ki-67, From Baseline to 6 Months
Change in proliferation as measured by Ki-67 immunocytochemical expression in breast epithelial cells obtained by random periareolar fine needle aspiration at baseline and at 6 months.
Measured: Baseline to 6 months
Secondary outcomes (6)
Change in Mammographic Breast Density
Change in mammographic density from baseline to 6 months, The Percent Breast Density is estimated using the Cumulus computer-assisted program to define a region that is at greater density than the remainder of the breast.
Measured: Baseline to 6 months
Change in Serum Estradiol Concentration
Change in serum concentration of estradiol from baseline to 6 months
Measured: Baseline to 6 months
Change in Serum Concentration of Bioavailable Estradiol
Change in serum concentration of bioavailable estradiol (adjusted for concentration of Sex Hormone Binding Globulin), from baseline to 6 months
Measured: Baseline to 6 months
Change in Serum Concentration of Testosterone
Change in serum concentration of Testosterone from baseline to 6 months
Measured: Baseline to 6 months
Reports of Hot Flashes as Assessed by the Loprinzi Hot Flash Scoring System
Problems with hot flashes were assessed by average number per day and intensity.
Measured: Baseline to up to 2 weeks post-treatment
Reports of Muscle/Joint Complaints as Assessed by the Validated HAQ II Questionnaire
The Health Assessment Questionnaire II (HAQ-II) measures interference in daily activities from arthralgias and joint pain. Range 0 - 4. A higher score indicates greater (i.e., "worse") interference.
Measured: Baseline to up to 2 weeks post-treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2009 (estimated)
- Study startFeb 2009
- Primary completionDec 2010
- Study completionDec 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by University of Kansas Medical CenterThe 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 2
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Kansas Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Carol Fabian, MD, University of Kansas Medical Center
- Investigators
- Carol Fabian, Principal investigator, University of Kansas Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00853996
- Sponsor's protocol ID
- NCI-2009-01116
- Other IDs
- 10588, NCT00855751, UW105-6-01, N01CN35153
- Status last verified
- Jan 2018
- First submitted
- 26 Feb 2009
- Last updated
- 17 Jan 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No: Individual data will not be shared; only summary assessments.
Study at a glance
From the registry record, last updated by the sponsor on 17 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Acolbifene in Pre-Menopausal Women at High Risk for Breast Cancer
- ClinicalTrials.gov ID
- NCT00853996
- Acronym / sponsor ID
- NCI-2009-01116
- Conditions
- Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- University of Kansas Medical CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Feb 2009
- Primary completion
- Dec 2010 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 2 Mar 2009 (estimated)
- Results
- Posted 13 Mar 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial is studying how well acolbifene works in preventing cancer in premenopausal women at high risk of breast cancer. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of acolbifene may stop cancer from growing or coming back.
Detailed description
PRIMARY OBJECTIVES:
- To determine the effect of six months of acolbifene 20 mg/day on Ki-67 in high risk premenopausal women with baseline hyperplasia +/- atypia and Ki-67 positivity of >= 2%..
SECONDARY OBJECTIVES:
- To determine the effect of six months of acolbifene 20 mg/day on mammographic breast density in high risk premenopausal women.
II. To determine the effect of six months of acolbifene 20 mg/day on serum levels of follicular phase bioavailable estradiol, and luteal phase progesterone, testosterone, and fasting IGF-1/IGFBP-3.
III. To determine the effect of six months of acolbifene 20 mg/day on epithelial cell cytomorphology and molecular markers such as ER, PgR, and pS2.
IV. To determine the effect of six months of acolbifene on markers of cardiovascular risk (C-reactive protein, functional AntiThrombin III, and fasting lipid profile) and bone turnover markers associated with bone mineral density gain or loss (serum osteocalcin and N-telopeptide crosslinks).
- To assess any increase in reported hot flashes, menstrual cycle irregularities, pelvic pain, musculoskeletal complaints, and fatigue from baseline.
OUTLINE:
Patients receive oral acolbifene hydrochloride once daily for 6 months in the absence of unacceptable toxicity.
Patients undergo symptom assessment (hot flashes, menstrual abnormalities, pelvic pain, muscle and joint pain, and fatigue) at baseline, 6-8 weeks, monthly for 6 months, and then at 2 weeks after completion of study treatment.
Patients undergo random periareolar fine needle aspiration between days 1-10 of menstrual cycle at baseline and at 6 months. Patients also undergo blood sample collection between days 1-10 and days 20-24 of menstrual cycle at baseline and at 6 months. Samples taken between days 1-10 of menstrual cycle are analyzed for Ki-67 expression, cytomorphology, molecular markers (estrogen receptor, progesterone receptor, and pS2 expression), and bioavailable estradiol levels. Samples taken between days 20-24 of menstrual cycle are analyzed for progesterone, testosterone, IGF-1, IGFBP-3, lipid profile, bone-turnover markers (osteocalcin and N-telopeptide crosslinks), C-reactive protein, and functional antithrombin III.
After completion of study treatment, patients are followed at 2 weeks.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Prevention (acolbifene hydrochloride) | Experimental | Drug: acolbifene hydrochloridePatients receive oral acolbifene hydrochloride once daily for 6 months in the absence of unacceptable toxicity. |
Who may qualify
- Ages
- 30 to 55 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (27 listed)
- Gail risk >= 1.7% and/or relative risk >= 3 times that for 5-year age group
- Premenopausal
- More than 6 months since initiating or discontinuing oral contraceptives
- At increased risk for breast cancer, as indicated by >= 1 of the following risk factors:
- BRCA1/2 mutation characterized as deleterious or of uncertain significance
Key exclusion criteria (12 listed)
- pregnant or nursing
- nursing within the past 6 months
- Known osteoporosis or severe osteopenia (T-score -2 or worse by DEXA)
- History of symptomatic endometriosis with pelvic pain, poorly controlled migraines, or hot flashes
- History of deep venous thrombosis
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 |
|---|---|---|
| acolbifene hydrochlorideAlso: EM-652.HCL, SCH 57068.HClGiven orally | Drug | Prevention (acolbifene hydrochloride) |
Primary outcome
Change in the Percentage of Breast Epithelial Cells Expressing Ki-67, From Baseline to 6 Months
Time frame: Baseline to 6 months
Change in proliferation as measured by Ki-67 immunocytochemical expression in breast epithelial cells obtained by random periareolar fine needle aspiration at baseline and at 6 months.
6 secondary outcomes
Change in Mammographic Breast Density
Time frame: Baseline to 6 months
Change in Serum Estradiol Concentration
Time frame: Baseline to 6 months
Change in Serum Concentration of Bioavailable Estradiol
Time frame: Baseline to 6 months
Change in Serum Concentration of Testosterone
Time frame: Baseline to 6 months
Reports of Hot Flashes as Assessed by the Loprinzi Hot Flash Scoring System
Time frame: Baseline to up to 2 weeks post-treatment
Reports of Muscle/Joint Complaints as Assessed by the Validated HAQ II Questionnaire
Time frame: Baseline to up to 2 weeks post-treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jan 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. Individual data will not be shared; only summary assessments.
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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.
Carol Fabian principal investigator
University of Kansas Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing acolbifene hydrochloride in people with Breast Cancer, run by University of Kansas Medical Center 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 27 inclusion and 12 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 17 Jan 2018. 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?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Mar 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 the Percentage of Breast Epithelial Cells Expressing Ki-67, From Baseline to 6 Months (time frame: Baseline to 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 17 Jan 2018.