Healthy, no Evidence of DiseasePhase 1NCT01077453
Letrozole in Preventing Breast Cancer in Healthy Postmenopausal Women at High Risk for Breast Cancer
A Phase 1 study testing letrozole, quality-of-life assessment and laboratory biomarker analysis in people with Healthy, no Evidence of Disease and Lobular Breast Carcinoma in Situ, run by National Cancer Institute (NCI) at 3 sites in United States.
Trial summary
This randomized phase I trial studies the side effects and the best dose of letrozole in preventing breast cancer in healthy postmenopausal women at high risk for breast cancer. Chemoprevention is the use of drugs to keep breast cancer from forming or coming back. Read more about this study
- Who is it for?
- Ages 35 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy, no Evidence of Disease, Lobular Breast Carcinoma in Situ
- What is being tested?
- letrozole, quality-of-life assessment 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
- 112 participants
- Where
- 3 sitesUnited States
- Study dates
- Mar 2010to Jun 2014
- 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 35 years and older
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy postmenopausal women at "high risk" for breast cancer will be eligible for the study; definition of menopause will be:
- Amenorrhea for at least 12 months, or
- History of hysterectomy and bilateral salpingo-oophorectomy, or
- At least 55 years of age with prior hysterectomy with or without oophorectomy, or
- Age 35 to 54 with a prior hysterectomy without oophorectomy OR with a status of ovaries unknown with documented follicle-stimulating hormone level demonstrating elevation in postmenopausal range
- "High risk" for breast cancer will be defined as:
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- Prior histologically confirmed lobular carcinoma in situ (LCIS) treated by local excision only, or
- At least 1.66% probability of invasive breast cancer within 5 years using the Breast Cancer Risk Assessment Tool
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1; Karnofsky 80% or above
- Leukocytes >= 3,000/uL
- Absolute neutrophil count >= 1,500/uL
- Platelets >= 100,000/uL
- Total bilirubin =< 2.0 mg/dL
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.0 X institutional ULN
- Creatinine =< 1 X institutional ULN
- Recent mammogram negative for breast cancer, Breast Imaging-Reporting and Data System (BIRADS) score < 3 (within the last 12 months)
- Ability to understand and the willingness to sign a written informed consent document; only potential participants with the ability to understand and the willingness to sign a written document will be presented with an informed consenting document
Who cannot join
- Women diagnosed with osteoporosis (previously or on screening dual-energy X-ray absorptiometry [DEXA] for this study) and not on a stable dose of long or short-acting bisphosphonates therapy for at least 3 months will be excluded from the study; women diagnosed with osteoporosis and on raloxifene (Evista) therapy will be excluded from the study; use of calcium and/or vitamin D for osteoporosis prevention or treatment is allowed; women with osteopenia will be allowed to participate in this study
- Have had invasive cancer within the past five years except non-melanoma skin cancer
- Evidence of suspicious of malignant disease on bilateral mammogram within the past year unless ruled out by further evaluation
- History of prior invasive breast cancer or intraductal carcinoma in situ, or history of prior radiation therapy to the chest or breast
- Participants may not be receiving any other investigational agents; participants may not be concurrently enrolled in another breast cancer prevention intervention trial
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to letrozole
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- 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
- Within 3 months since prior estrogen or progesterone replacement therapy, oral contraceptives, androgens, luteinizing hormone-releasing hormone analogs, prolactin inhibitors, or antiandrogens
- Within 3 months since prior tamoxifen, raloxifene, or other selective estrogen-receptor modulators
- Within 3 months since regular use (more than 2 times a week) of prior estrogenic supplements or herbal remedies
- History of bleeding or clotting disorder; current or recent (within 3 months) use of Coumadin, Plavix or other systemic anticoagulant other than aspirin is not permitted if subject chooses to participate in the optional RPFNA procedure; if a subject chooses not to participate in the RPFNA procedure, prior or current treatment with systemic anticoagulants is permitted
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Mayo Clinic
Rochester, Minnesota, 55905
Arizona Cancer Center - Tucson
Tucson, Arizona, 85724-5024
University of Arizona Health Sciences Center
Tucson, Arizona, 85724
About this study
Official title: Phase I Dose-Finding Trial of Letrozole in Postmenopausal Women at High Risk for Breast Cancer
This randomized phase I trial studies the side effects and the best dose of letrozole in preventing breast cancer in healthy postmenopausal women at high risk for breast cancer. Chemoprevention is the use of drugs to keep breast cancer from forming or coming back. The use of letrozole may keep cancer from forming in healthy postmenopausal women at high risk for breast cancer.
Read the detailed description
PRIMARY OBJECTIVES:
- Compare the effect of lower and intermittent doses of letrozole to standard letrozole therapy on estrogen suppression in postmenopausal women at high risk for developing breast cancer.
SECONDARY OBJECTIVES:
- Comparison of the effect of lower and intermittent doses of letrozole to standard therapy on signs and symptoms of estrogen deficiency, including menopausal symptoms, serum lipid profile, and serum marker of bone turnover.
II. Comparison of the effect of lower and intermittent doses of letrozole to standard therapy on nuclear chromatin abnormality of breast epithelial cells collected by random periareolar fine needle aspiration (RPFNA).
TERTIARY OBJECTIVES:
- Determine the prevalence of breast cancer stem cells in the fine needle breast aspirates and explore the potential intervention effect on the prevalence of breast cancer stem cells.
OUTLINE: Patients are randomized to 1 of 4 treatment arms.
ARM I: Patients receive 2.5 mg of letrozole orally (PO) thrice weekly for 6 months.
ARM II: Patients receive 1.0 mg of letrozole PO thrice weekly for 6 months.
ARM III: Patients receive 0.25 mg of letrozole PO thrice weekly for 6 months.
ARM IV: Patients receive 2.5 mg of letrozole PO once daily for 6 months.
After completion of study treatment, patients are followed up at week 30.
- Being tested
- letrozole, quality-of-life assessment, laboratory biomarker analysis
- Medical subject headings
- Breast Carcinoma In Situ
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
letrozoleDrug
Also called CGS 20267, Femara, LTZ
Given orally
quality-of-life assessmentOther
Also called quality of life assessment
Ancillary studies
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Arm I (2.5 mg letrozole) | Experimental | Patients receive 2.5 mg of letrozole PO thrice weekly for 6 months. Receives: Drug: letrozole; Other: quality-of-life assessment; Other: laboratory biomarker analysis |
| Arm II (1.0 mg letrozole) | Experimental | Patients receive 1.0 mg of letrozole PO thrice weekly for 6 months. Receives: Drug: letrozole; Other: quality-of-life assessment; Other: laboratory biomarker analysis |
| Arm III (0.25 mg letrozole) | Experimental | Patients receive 0.25 mg of letrozole PO thrice weekly for 6 months. Receives: Drug: letrozole; Other: quality-of-life assessment; Other: laboratory biomarker analysis |
| Arm IV (2.5 mg letrozole) | Experimental | Patients receive 2.5 mg of letrozole PO once daily for 6 months. Receives: Drug: letrozole; Other: quality-of-life assessment; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of serum estradiol suppression in postmenopausal women at high risk for breast cancer
Three one-sided two-sample t-tests will be conducted on the ratios of the mean percentage of suppression simultaneously to test for non-inferiority. A multivariate t-distribution is used to derive the critical value and the power.
Measured: Baseline to week 30
Secondary outcomes (4)
Change in serum estrone levels
Three one-sided two-sample t-tests will be performed to evaluate the ratio of the mean changes (or percentage of changes) of each of the three intermittent dosing groups to that of the standard therapy control group simultaneously for each of the endpoints at an overall significance level of 5%.
Measured: Baseline to week 30
Change in serum testosterone levels
Three one-sided two-sample t-tests will be performed to evaluate the ratio of the mean changes (or percentage of changes) of each of the three intermittent dosing groups to that of the standard therapy control group simultaneously for each of the endpoints at an overall significance level of 5%.
Measured: Baseline to week 30
Menopausal symptoms as assessed by quality of life measures, as assessed by Medical Outcomes Study 36-item Short Form Health Survey (SF-36) and Menopause Specific Quality of Life Questionnaire (MENQOL)
Measured: Up to week 30
Nuclear chromatin abnormality as assessed by karyometry
Measured: Up to week 30
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2010 (estimated)
- Study startMar 2010
- Primary completionJun 2014
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 Healthy, no Evidence of DiseaseStudies 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 112 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Ana Lopez, Principal investigator, University of Arizona Health Sciences Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01077453
- Sponsor's protocol ID
- NCI-2013-00757
- Other IDs
- NCI-2013-00757, 09-0869-04, UAZ08-12-02, N01CN35158, P30CA023074
- Status last verified
- Oct 2014
- First submitted
- 26 Feb 2010
- Last updated
- 20 Oct 2014
- Results posted
- No
Publications
Lopez AM, Pruthi S, Boughey JC, Perloff M, Hsu CH, Lang JE, Ley M, Frank D, Taverna JA, Chow HH. Double-Blind, Randomized Trial of Alternative Letrozole Dosing Regimens in Postmenopausal Women with Increased Breast Cancer Risk. Cancer Prev Res (Phila). 2016 Feb;9(2):142-8. doi: 10.1158/1940-6207.CAPR-15-0322. Epub 2015 Dec 14.
PubMed 26667449
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Dose-Finding Trial of Letrozole in Postmenopausal Women at High Risk for Breast Cancer
- ClinicalTrials.gov ID
- NCT01077453
- Acronym / sponsor ID
- NCI-2013-00757
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 112 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Mar 2010
- Primary completion
- Jun 2014 (actual)
- First posted
- 1 Mar 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.
This randomized phase I trial studies the side effects and the best dose of letrozole in preventing breast cancer in healthy postmenopausal women at high risk for breast cancer. Chemoprevention is the use of drugs to keep breast cancer from forming or coming back. The use of letrozole may keep cancer from forming in healthy postmenopausal women at high risk for breast cancer.
Detailed description
PRIMARY OBJECTIVES:
- Compare the effect of lower and intermittent doses of letrozole to standard letrozole therapy on estrogen suppression in postmenopausal women at high risk for developing breast cancer.
SECONDARY OBJECTIVES:
- Comparison of the effect of lower and intermittent doses of letrozole to standard therapy on signs and symptoms of estrogen deficiency, including menopausal symptoms, serum lipid profile, and serum marker of bone turnover.
II. Comparison of the effect of lower and intermittent doses of letrozole to standard therapy on nuclear chromatin abnormality of breast epithelial cells collected by random periareolar fine needle aspiration (RPFNA).
TERTIARY OBJECTIVES:
- Determine the prevalence of breast cancer stem cells in the fine needle breast aspirates and explore the potential intervention effect on the prevalence of breast cancer stem cells.
OUTLINE: Patients are randomized to 1 of 4 treatment arms.
ARM I: Patients receive 2.5 mg of letrozole orally (PO) thrice weekly for 6 months.
ARM II: Patients receive 1.0 mg of letrozole PO thrice weekly for 6 months.
ARM III: Patients receive 0.25 mg of letrozole PO thrice weekly for 6 months.
ARM IV: Patients receive 2.5 mg of letrozole PO once daily for 6 months.
After completion of study treatment, patients are followed up at week 30.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Arm I (2.5 mg letrozole) | Experimental | Drug: letrozole, Other: quality-of-life assessment, Other: laboratory biomarker analysisPatients receive 2.5 mg of letrozole PO thrice weekly for 6 months. |
| Arm II (1.0 mg letrozole) | Experimental | Drug: letrozole, Other: quality-of-life assessment, Other: laboratory biomarker analysisPatients receive 1.0 mg of letrozole PO thrice weekly for 6 months. |
| Arm III (0.25 mg letrozole) | Experimental | Drug: letrozole, Other: quality-of-life assessment, Other: laboratory biomarker analysisPatients receive 0.25 mg of letrozole PO thrice weekly for 6 months. |
| Arm IV (2.5 mg letrozole) | Experimental | Drug: letrozole, Other: quality-of-life assessment, Other: laboratory biomarker analysisPatients receive 2.5 mg of letrozole PO once daily for 6 months. |
Who may qualify
- Ages
- 35 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Healthy postmenopausal women at "high risk" for breast cancer will be eligible for the study; definition of menopause will be:
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1; Karnofsky 80% or above
- Leukocytes >= 3,000/uL
- Absolute neutrophil count >= 1,500/uL
- Platelets >= 100,000/uL
Key exclusion criteria (11 listed)
- Women diagnosed with osteoporosis (previously or on screening dual-energy X-ray absorptiometry [DEXA] for this study) and not on a stable dose of long or short-acting bisphosphonates therapy for at least 3 months will be excluded from the study; women diagnosed with osteoporosis and on raloxifene (Evista) therapy will be excluded from the study; use of calcium and/or vitamin D for osteoporosis prevention or treatment is allowed; women with osteopenia will be allowed to participate in this study
- Have had invasive cancer within the past five years except non-melanoma skin cancer
- Evidence of suspicious of malignant disease on bilateral mammogram within the past year unless ruled out by further evaluation
- History of prior invasive breast cancer or intraductal carcinoma in situ, or history of prior radiation therapy to the chest or breast
- Participants may not be receiving any other investigational agents; participants may not be concurrently enrolled in another breast cancer prevention intervention trial
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 |
|---|---|---|
| letrozoleAlso: CGS 20267, Femara, LTZGiven orally | Drug | Arm I (2.5 mg letrozole), Arm II (1.0 mg letrozole), Arm III (0.25 mg letrozole), Arm IV (2.5 mg letrozole) |
| quality-of-life assessmentAlso: quality of life assessmentAncillary studies | Other | Arm I (2.5 mg letrozole), Arm II (1.0 mg letrozole), Arm III (0.25 mg letrozole), Arm IV (2.5 mg letrozole) |
| laboratory biomarker analysisCorrelative studies | Other | Arm I (2.5 mg letrozole), Arm II (1.0 mg letrozole), Arm III (0.25 mg letrozole), Arm IV (2.5 mg letrozole) |
Primary outcome
Percentage of serum estradiol suppression in postmenopausal women at high risk for breast cancer
Time frame: Baseline to week 30
Three one-sided two-sample t-tests will be conducted on the ratios of the mean percentage of suppression simultaneously to test for non-inferiority. A multivariate t-distribution is used to derive the critical value and the power.
4 secondary outcomes
Change in serum estrone levels
Time frame: Baseline to week 30
Change in serum testosterone levels
Time frame: Baseline to week 30
Menopausal symptoms as assessed by quality of life measures, as assessed by Medical Outcomes Study 36-item Short Form Health Survey (SF-36) and Menopause Specific Quality of Life Questionnaire (MENQOL)
Time frame: Up to week 30
Nuclear chromatin abnormality as assessed by karyometry
Time frame: Up to week 30
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 20 Oct 2014.
- Derived from this study: PubMed 26667449Lopez AM, Pruthi S, Boughey JC, Perloff M, Hsu CH, Lang JE, Ley M, Frank D, Taverna JA, Chow HH. Double-Blind, Randomized Trial of Alternative Letrozole Dosing Regimens in Postmenopausal Women with Increased Breast Cancer Risk. Cancer Prev Res (Phila). 2016 Feb;9(2):142-8. doi: 10.1158/1940-6207.CAPR-15-0322. Epub 2015 Dec 14.
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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.
Ana Lopez principal investigator
University of Arizona Health Sciences Center
3 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 letrozole, quality-of-life assessment and laboratory biomarker analysis in people with Healthy, no Evidence of Disease and Lobular Breast Carcinoma in Situ, run by National Cancer Institute (NCI) at 3 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 17 inclusion and 11 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 20 Oct 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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?
Percentage of serum estradiol suppression in postmenopausal women at high risk for breast cancer (time frame: Baseline to week 30). 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 NCT01077453, 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 20 Oct 2014.