Atypical Ductal Breast HyperplasiaPhase 1NCT00637481
A Phase I Prevention Study of Atorvastatin in Women at Increased Risk for Breast Cancer
A Phase 1 study testing atorvastatin calcium and laboratory biomarker analysis in people with Atypical Ductal Breast Hyperplasia and Breast Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Chemoprevention is the use of certain drugs to keep cancer from forming. The use of atorvastatin (Lipitor) may prevent breast cancer. This randomized phase I trial is studying the best dose of atorvastatin in preventing breast cancer in women at increased risk for breast cancer. Read more about this study
- Who is it for?
- Ages 18 to 72 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Atypical Ductal Breast Hyperplasia, Breast Cancer, Ductal Breast Carcinoma in Situ
- What is being tested?
- atorvastatin calcium and laboratory biomarker analysis
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 66 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2008to Oct 2012
- 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 72 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Women at increased risk for breast cancer, defined by one of the following:
- 5 year projected Gail risk of greater than 1.67%
- Previous diagnosis of atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS) (per participating institution's pathology review), or ductal carcinoma in situ (participants could have received any type of surgery and radiation as long as they have an intact opposite breast)
- The participant must have been properly informed of the study and must sign an informed consent to be able to be enrolled in the study; the informed consent document must be signed, witnessed, and dated prior to start of the study
- Normal physical exam and bilateral mammogram that shows no evidence of suspicious, malignant disease, or uncharacterized lesions within last 12 months and no evidence of any active other cancer
- Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky greater than or equal to 70%)
Show all 13Show fewer
- Leukocytes greater than 3,000/uL
- Platelets greater than 100,000/uL
- Total bilirubin within normal institutional limits
- AST (SGOT)or /ALT (SGPT) =< 1.5 X institutional ULN
- Creatinine within normal institutional limits
- CPK, PTT, PT within normal institutional limits (up to 1 month prior to randomization)
- The effects of atorvastatin on the developing human fetus at the recommended therapeutic dose are unknown; for this reason, women of child-bearing potential must agree to use adequate contraception (barrier method of birth control (IUD); abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately
Who cannot join
- Any type of active invasive cancer
- Bilateral mastectomy
- Use of oral contraceptives; androgens; luteinizing-hormone-releasing-hormone (LHRH) analogs, prolactin inhibitors, antiandrogens, tamoxifen, raloxifen, or aromatase inhibitors; women who discontinue these drugs at least 3 months prior to study enrollment will be eligible
- Chronic medical condition that requires regular use of statins or steroids (unless participants have discontinued these drugs 1 month prior to enrollment)
- Participants may not be receiving any other investigational agents
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to atorvastatin
- Psychiatric condition, including history of clinical depression, or addictive disorder that would preclude obtaining informed consent or would interfere with compliance; 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
- Pregnant women are excluded from this study because atorvastatin is a Class X agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with atorvastatin breast feeding should be discontinued if the mother is treated with atorvastatin
Trial locations and contacts
1 site in 1 country.
About this study
Chemoprevention is the use of certain drugs to keep cancer from forming. The use of atorvastatin (Lipitor) may prevent breast cancer. This randomized phase I trial is studying the best dose of atorvastatin in preventing breast cancer in women at increased risk for breast cancer.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the minimum biological effective dose (MBED) of atorvastatin required to induce modulation in the proliferation marker, Ki-67, in breast tissue of women who are at high risk to develop breast cancer. We will evaluate pre- and post atorvastatin treatment (4 dose levels) expression of Ki-67 in samples obtained via FNA from breast tissue of women at high risk for breast cancer. This specific aim tests the hypothesis that treatment with atorvastatin will induce a decrease in Ki-67.
SECONDARY OBJECTIVES:
- To evaluate atorvastatin induced modulation of breast cancer biomarkers markers (EGFR, P-EGFR, ER, p21, p27, bcl-2, CC3, cytology) and drug related markers (LXR, total cholesterol, LDL, HDL, CRP) in women who are at high risk to develop breast cancer.
II. To determine plasma and tissue levels of atorvastatin and two of its hydroxylated metabolites (ohydroxyatorvastatin and p-hydroxyatorvastatin) in women who are treated with atorvastatin and to correlate these levels with Ki-67 levels. III. To correlate changes in Ki-67 and the above-described panel of biomarkers with HMG-CoA reductase genotype.
OUTLINE: Participants are randomized to 1 of 4 arms.
ARM I: Participants receive oral atorvastatin once daily for 3 months.
ARM II: Participants receive oral atorvastatin (at a higher dose than in arm I) once daily for 3 months.
ARM III: Participants receive oral atorvastatin (at a higher dose than in arm II) once daily for 3 months.
ARM IV: Participants do not receive treatment. Participants undergo blood sample collection and fine needle aspiration of breast tissue at baseline and at 3 months for correlative biomarker studies.
- Conditions
- Atypical Ductal Breast Hyperplasia, Breast Cancer, Ductal Breast Carcinoma in Situ, Lobular Breast Carcinoma in Situ
- Being tested
- atorvastatin calcium, laboratory biomarker analysis
- Medical subject headings
- Carcinoma, Intraductal, Noninfiltrating, Breast Neoplasms, Breast Carcinoma In Situ
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
atorvastatin calciumDrug
Also called CI-981, Lipitor
Given orally
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Arm I (lower dose atorvastatin calcium) | Experimental | Participants receive oral atorvastatin once daily for 3 months. Receives: Drug: atorvastatin calcium; Other: laboratory biomarker analysis |
| Arm II (atorvastatin calcium) | Experimental | Participants receive oral atorvastatin (at a higher dose than in arm I) once daily for 3 months. Receives: Drug: atorvastatin calcium; Other: laboratory biomarker analysis |
| Arm III (higher dose atorvastatin calcium) | Experimental | Participants receive oral atorvastatin (at a higher dose than in arm II) once daily for 3 months. Receives: Drug: atorvastatin calcium; Other: laboratory biomarker analysis |
| Arm IV (no intervention) | Other | Participants do not receive treatment. Participants undergo blood sample collection and fine needle aspiration of breast tissue at baseline and at 3 months for correlative biomarker studies. Receives: Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Atorvastatin induced changes in proliferation rate measured by Ki-67
A single proliferation rate at each time period is calculated for each participant based on the proportion cells expressing KI-67.
Measured: Baseline to 3 months
Secondary outcomes (7)
Cytologic evaluation of FNA samples
Measured: Baseline
Cytologic evaluation of FNA samples
Measured: 3 months
Proliferation and apoptosis analysis of FNA samples
Measured: Baseline
Proliferation and apoptosis analysis of FNA samples
Measured: 3 months
Inflammatory and lipid profile markers
Measured: Up to 3 months
Genotypic analysis
Measured: Baseline
Measurement of atorvastatin and its metabolites in serum and breast tissue
Measured: Up to 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2008 (estimated)
- Study startMar 2008
- Primary completionOct 2012
- Study completionOct 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Atypical Ductal Breast HyperplasiaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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
- None (open label)
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Banu Arun, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00637481
- Sponsor's protocol ID
- NCI-2009-00859
- Other IDs
- NCI-2009-00859, CDR0000653466, 2006-0185, MDA05-6-01, N01CN35159, P30CA016672
- Status last verified
- Dec 2016
- First submitted
- 17 Mar 2008
- Last updated
- 29 Dec 2016
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Prevention Study of Atorvastatin in Women at Increased Risk for Breast Cancer
- ClinicalTrials.gov ID
- NCT00637481
- Acronym / sponsor ID
- NCI-2009-00859
- Conditions
- Atypical Ductal Breast Hyperplasia, Breast Cancer, Ductal Breast Carcinoma in Situ, Lobular Breast Carcinoma in Situ
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 66 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Mar 2008
- Primary completion
- Oct 2012 (actual)
- Study completion
- Oct 2012 (actual)
- First posted
- 18 Mar 2008 (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.
Chemoprevention is the use of certain drugs to keep cancer from forming. The use of atorvastatin (Lipitor) may prevent breast cancer. This randomized phase I trial is studying the best dose of atorvastatin in preventing breast cancer in women at increased risk for breast cancer.
Detailed description
PRIMARY OBJECTIVES:
- To determine the minimum biological effective dose (MBED) of atorvastatin required to induce modulation in the proliferation marker, Ki-67, in breast tissue of women who are at high risk to develop breast cancer. We will evaluate pre- and post atorvastatin treatment (4 dose levels) expression of Ki-67 in samples obtained via FNA from breast tissue of women at high risk for breast cancer. This specific aim tests the hypothesis that treatment with atorvastatin will induce a decrease in Ki-67.
SECONDARY OBJECTIVES:
- To evaluate atorvastatin induced modulation of breast cancer biomarkers markers (EGFR, P-EGFR, ER, p21, p27, bcl-2, CC3, cytology) and drug related markers (LXR, total cholesterol, LDL, HDL, CRP) in women who are at high risk to develop breast cancer.
II. To determine plasma and tissue levels of atorvastatin and two of its hydroxylated metabolites (ohydroxyatorvastatin and p-hydroxyatorvastatin) in women who are treated with atorvastatin and to correlate these levels with Ki-67 levels. III. To correlate changes in Ki-67 and the above-described panel of biomarkers with HMG-CoA reductase genotype.
OUTLINE: Participants are randomized to 1 of 4 arms.
ARM I: Participants receive oral atorvastatin once daily for 3 months.
ARM II: Participants receive oral atorvastatin (at a higher dose than in arm I) once daily for 3 months.
ARM III: Participants receive oral atorvastatin (at a higher dose than in arm II) once daily for 3 months.
ARM IV: Participants do not receive treatment. Participants undergo blood sample collection and fine needle aspiration of breast tissue at baseline and at 3 months for correlative biomarker studies.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Arm I (lower dose atorvastatin calcium) | Experimental | Drug: atorvastatin calcium, Other: laboratory biomarker analysisParticipants receive oral atorvastatin once daily for 3 months. |
| Arm II (atorvastatin calcium) | Experimental | Drug: atorvastatin calcium, Other: laboratory biomarker analysisParticipants receive oral atorvastatin (at a higher dose than in arm I) once daily for 3 months. |
| Arm III (higher dose atorvastatin calcium) | Experimental | Drug: atorvastatin calcium, Other: laboratory biomarker analysisParticipants receive oral atorvastatin (at a higher dose than in arm II) once daily for 3 months. |
| Arm IV (no intervention) | Other | Other: laboratory biomarker analysisParticipants do not receive treatment. Participants undergo blood sample collection and fine needle aspiration of breast tissue at baseline and at 3 months for correlative biomarker studies. |
Who may qualify
- Ages
- 18 to 72 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Women at increased risk for breast cancer, defined by one of the following:
- The participant must have been properly informed of the study and must sign an informed consent to be able to be enrolled in the study; the informed consent document must be signed, witnessed, and dated prior to start of the study
- Normal physical exam and bilateral mammogram that shows no evidence of suspicious, malignant disease, or uncharacterized lesions within last 12 months and no evidence of any active other cancer
- Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky greater than or equal to 70%)
- Leukocytes greater than 3,000/uL
Key exclusion criteria (8 listed)
- Any type of active invasive cancer
- Bilateral mastectomy
- Use of oral contraceptives; androgens; luteinizing-hormone-releasing-hormone (LHRH) analogs, prolactin inhibitors, antiandrogens, tamoxifen, raloxifen, or aromatase inhibitors; women who discontinue these drugs at least 3 months prior to study enrollment will be eligible
- Chronic medical condition that requires regular use of statins or steroids (unless participants have discontinued these drugs 1 month prior to enrollment)
- Participants may not be receiving any other investigational agents
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 |
|---|---|---|
| atorvastatin calciumAlso: CI-981, LipitorGiven orally | Drug | Arm I (lower dose atorvastatin calcium), Arm II (atorvastatin calcium), Arm III (higher dose atorvastatin calcium) |
| laboratory biomarker analysisCorrelative studies | Other | Arm I (lower dose atorvastatin calcium), Arm II (atorvastatin calcium), Arm III (higher dose atorvastatin calcium), Arm IV (no intervention) |
Primary outcome
Atorvastatin induced changes in proliferation rate measured by Ki-67
Time frame: Baseline to 3 months
A single proliferation rate at each time period is calculated for each participant based on the proportion cells expressing KI-67.
7 secondary outcomes
Cytologic evaluation of FNA samples
Time frame: Baseline
Cytologic evaluation of FNA samples
Time frame: 3 months
Proliferation and apoptosis analysis of FNA samples
Time frame: Baseline
Proliferation and apoptosis analysis of FNA samples
Time frame: 3 months
Inflammatory and lipid profile markers
Time frame: Up to 3 months
Genotypic analysis
Time frame: Baseline
Measurement of atorvastatin and its metabolites in serum and breast tissue
Time frame: Up to 3 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 29 Dec 2016.
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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.
Banu Arun principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing atorvastatin calcium and laboratory biomarker analysis in people with Atypical Ductal Breast Hyperplasia and Breast Cancer, run by National Cancer Institute (NCI) 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 13 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: finished, as of the sponsor's last update on 29 Dec 2016. 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 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?
Atorvastatin induced changes in proliferation rate measured by Ki-67 (time frame: Baseline to 3 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 29 Dec 2016.