Breast CancerEarly Phase 1NCT00651976
Letrozole in Treating Postmenopausal Women With Stage I, II or III Breast Cancer That Can Be Removed by Surgery
A Early Phase 1 study testing letrozole, Blood Collection and biopsy/lumpectomy/mastectomy in people with Breast Cancer, run by Vanderbilt-Ingram Cancer Center at 5 sites in United States.
Trial summary
RATIONALE: Hormone therapy using letrozole may fight breast cancer by lowering the amount of estrogen the body makes. Giving letrozole before surgery allows us to monitor the effects of letrozole on the tumor on a molecular level and determine markers of response to treatment. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- letrozole, Blood Collection and biopsy/lumpectomy/mastectomy
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 213 participants
- Where
- 5 sitesUnited States
- Study dates
- Mar 2008to Sep 2018
- 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
DISEASE CHARACTERISTICS:
- Diagnosis of invasive breast cancer
- Clinical stage I, II, or III disease
- Resectable disease
- Measurable disease, defined as a mass that can be reproducibly measured by physical examination and/or ultrasound and is at least 1 cm in size by ultrasound
- Patients with measurable residual tumor at the primary site allowed
- Estrogen receptor-positive tumor by immunohistochemistry (IHC)
- HER2-negative tumor by Herceptest (0 or +1) OR HER2 not overexpressed by fluorescence in situ hybridization (FISH)
- Planning to undergo surgical treatment with either segmental resection or total mastectomy with or without lymph node evaluation
- Must have core biopsies from the time of diagnosis available (may include sections of paraffin-embedded material)
- Prior contralateral breast cancer allowed provided there is no evidence of recurrence of the initial primary breast cancer
- Patients with locally advanced disease who are candidates for preoperative chemotherapy at the time of initial evaluation are not eligible
- Locally advanced disease is defined by any of the following:
- Primary tumor ≥ 5 cm (T3)
- Tumor of any size with direct extension to the chest wall or skin (T4a-c)
- Inflammatory breast cancer (T4d)
- Fixed axillary lymph node metastases (N2)
- Metastasis to ipsilateral internal mammary node (N3)
- No locally recurrent disease
- No evidence of distant metastatic disease (i.e., lung, liver, bone, or brain metastases)
PATIENT CHARACTERISTICS:
- ECOG performance status 0-1
- Postmenopausal, as defined by any of the following:
- 55 years of age and over
- Under 55 years of age and meets 1 of the following criteria:
- Amenorrheic for at least 12 months
- Follicle-stimulating hormone (FSH) ≥ 40 IU/L and estradiol levels ≤ 20 IU/L
- Has undergone prior bilateral oophorectomy or radiation castration AND has been amenorrheic for at least 6 months
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- SGOT and SGPT ≤ 1.5 times ULN
- Creatinine ≤ 1.5 t times ULN
- Able to swallow and retain oral medication
- No serious medical illness that, in the judgment of the treating physician, places the patient at high risk for operative mortality
- No malabsorption syndrome, ulcerative colitis, or other disease significantly affecting gastrointestinal function
- No other malignancy within the past 5 years except for completely resected nonmelanoma skin cancer or successfully treated in situ carcinoma
- No dementia, altered mental status, or any psychiatric condition that would preclude the understanding or rendering of informed consent
- No severe uncontrolled malabsorption condition or disease (i.e., grade II/III diarrhea, severe malnutrition, or short gut syndrome)
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- At least 21 days since prior tamoxifen or raloxifene as a preventive agent
- At least 7 days since prior hormone replacement therapy (e.g., conjugated estrogens [Premarin])
- No prior resection of the stomach or small bowel
- More than 30 days or 5 half-lives, whichever is longer, since prior investigational drugs
- No prior chemotherapy for this primary breast cancer
- No other concurrent investigational agents
- No other concurrent anticancer therapy (e.g., chemotherapy, radiotherapy, immunotherapy, hormonal therapy, or any other biologic therapy)
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Emory University
Atlanta, Georgia
Vanderbilt-Ingram Cancer Center, One Hundred Oaks
Nashville, Tennessee, 37204
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232-6838
Allegheny Cancer Center
Pittsburgh, Pennsylvania, 15212
Surgical Associates, Inc.
Tulsa, Oklahoma, 74136
About this study
Official title: Pre-Surgical Trial of Letrozole in Post-Menopausal Patients With Operable Hormone-Sensitive Breast Cancer (Spore)
RATIONALE: Hormone therapy using letrozole may fight breast cancer by lowering the amount of estrogen the body makes. Giving letrozole before surgery allows us to monitor the effects of letrozole on the tumor on a molecular level and determine markers of response to treatment.
PURPOSE: This study will show us how well letrozole works in treating postmenopausal women with stage I, II or III breast cancer that can be removed by surgery.
Read the detailed description
OBJECTIVES:
Primary To determine that in breast tumors that continue to exhibit high proliferation (i.e., Ki67) upon hormone deprivation (with letrozole), their gene expression and/or a mutational or proteomic signatures will harbor molecules or 'pathways' that are biomarkers of resistance to endocrine therapy or a cause of it.
The ultimate goal of these aims is to identify clinically-targetable pathways which can be exploited to enhance responses and survival in patients with ER+ breast cancer.
OUTLINE: Patients receive oral letrozole once daily for 7-21 days in the absence of disease progression or unacceptable toxicity. Within 24 hours after the last dose of letrozole, patients undergo total mastectomy or segmental resection with lymph node evaluation.
Pre-treatment diagnostic breast tissue is obtained. Patients undergo treatment and then undergo standard of care mastectomy or lumpectomy. Pre and post treatment tumor tissue samples are analyzed for Ki67, P-ER, ER, progesterone receptor (PR), and caspase 3 by immunohistochemistry; and RNA microarray.
- Conditions
- Breast Cancer
- Being tested
- letrozole, Blood Collection, biopsy/lumpectomy/mastectomy
- Keywords
- stage IA breast cancer, stage IB breast cancer, stage II breast cancer, stage III breast cancer, HER2-negative breast cancer, estrogen receptor-positive breast cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
letrozoleDrug
Take by mouth at a dose of 2.5 mg on days 7-21
Blood CollectionOther
Blood used for gene expression analysis and reverse transcriptase-polymerase chain reaction
biopsy/lumpectomy/mastectomyProcedure or surgery
Tissue collection,Surgery to remove tumor, Tumor tissues used for laboratory biomarker analysis
| Study group | Role | What they receive |
|---|---|---|
| treatment | Experimental | Not described Receives: Drug: letrozole; Other: Blood Collection; Procedure: biopsy/lumpectomy/mastectomy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ki67 index measured in hormone receptor-positive breast cancers compared to those that are hormone receptor-negative
Ki67 index is measured by counting the percentage of cells staining for Ki67 in a section of breast tissue. The number of stained cells will be compared in tissue that is hormone receptor-positive tissue to tissue that is hormone receptor negative.
Measured: day 7 to day 21
Secondary outcomes (2)
In situ apoptotic effect of letrozole
Measured by level of capase-3 in post-treatment breast tissue.
Measured: day 7 to day 21
Identification of a recurrence risk biomarker profile using RNA microarray
RNA will be extracted from pre- and post-treatment breast tissue and will be compared with the Ki67 index
Measured: day 7 to day 21
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Apr 2008 (estimated)
- Study startMar 2008
- Primary completionSep 2018
- Study completionSep 2018
Why it stopped: funding unavailable
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- 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
- 213 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt-Ingram Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Ingrid Meszoely, MD, Vanderbilt-Ingram Cancer Center
- Investigators
- Ingrid Meszoely, MD, Principal investigator, Vanderbilt-Ingram Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00651976
- Sponsor's protocol ID
- VICC BRE 0776
- Other IDs
- P50CA098131, P30CA068485, VU-VICC-BRE-0776, VU-VICC-IRB-080064
- Status last verified
- Oct 2018
- First submitted
- 2 Apr 2008
- Last updated
- 15 Oct 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pre-Surgical Trial of Letrozole in Post-Menopausal Patients With Operable Hormone-Sensitive Breast Cancer (Spore)
- ClinicalTrials.gov ID
- NCT00651976
- Acronym / sponsor ID
- VICC BRE 0776
- Conditions
- Breast Cancer
- Keywords
- stage IA breast cancer, stage IB breast cancer, stage II breast cancer, stage III breast cancer, HER2-negative breast cancer, estrogen receptor-positive breast cancer
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: funding unavailable
- Enrolment
- 213 participants (actual)
- Lead sponsor
- Vanderbilt-Ingram Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Mar 2008
- Primary completion
- Sep 2018 (actual)
- Study completion
- Sep 2018 (actual)
- First posted
- 3 Apr 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.
RATIONALE: Hormone therapy using letrozole may fight breast cancer by lowering the amount of estrogen the body makes. Giving letrozole before surgery allows us to monitor the effects of letrozole on the tumor on a molecular level and determine markers of response to treatment.
PURPOSE: This study will show us how well letrozole works in treating postmenopausal women with stage I, II or III breast cancer that can be removed by surgery.
Detailed description
OBJECTIVES:
Primary To determine that in breast tumors that continue to exhibit high proliferation (i.e., Ki67) upon hormone deprivation (with letrozole), their gene expression and/or a mutational or proteomic signatures will harbor molecules or 'pathways' that are biomarkers of resistance to endocrine therapy or a cause of it.
The ultimate goal of these aims is to identify clinically-targetable pathways which can be exploited to enhance responses and survival in patients with ER+ breast cancer.
OUTLINE: Patients receive oral letrozole once daily for 7-21 days in the absence of disease progression or unacceptable toxicity. Within 24 hours after the last dose of letrozole, patients undergo total mastectomy or segmental resection with lymph node evaluation.
Pre-treatment diagnostic breast tissue is obtained. Patients undergo treatment and then undergo standard of care mastectomy or lumpectomy. Pre and post treatment tumor tissue samples are analyzed for Ki67, P-ER, ER, progesterone receptor (PR), and caspase 3 by immunohistochemistry; and RNA microarray.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| treatment | Experimental | Drug: letrozole, Other: Blood Collection, Procedure: biopsy/lumpectomy/mastectomy |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| letrozoleTake by mouth at a dose of 2.5 mg on days 7-21 | Drug | treatment |
| Blood CollectionBlood used for gene expression analysis and reverse transcriptase-polymerase chain reaction | Other | treatment |
| biopsy/lumpectomy/mastectomyTissue collection,Surgery to remove tumor, Tumor tissues used for laboratory biomarker analysis | Procedure or surgery | treatment |
Primary outcome
Ki67 index measured in hormone receptor-positive breast cancers compared to those that are hormone receptor-negative
Time frame: day 7 to day 21
Ki67 index is measured by counting the percentage of cells staining for Ki67 in a section of breast tissue. The number of stained cells will be compared in tissue that is hormone receptor-positive tissue to tissue that is hormone receptor negative.
2 secondary outcomes
In situ apoptotic effect of letrozole
Time frame: day 7 to day 21
Identification of a recurrence risk biomarker profile using RNA microarray
Time frame: day 7 to day 21
Results and safety
The study was stopped early (reason given: funding unavailable). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2018.
- Vanderbilt-Ingram Cancer Center, Find a Clinical TrialLink 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.
Ingrid Meszoely, MD principal investigator
Vanderbilt-Ingram Cancer Center
5 sites 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 letrozole, Blood Collection and biopsy/lumpectomy/mastectomy in people with Breast Cancer, run by Vanderbilt-Ingram Cancer Center at 5 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?
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 15 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 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?
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: funding unavailable). 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?
Ki67 index measured in hormone receptor-positive breast cancers compared to those that are hormone receptor-negative (time frame: day 7 to day 21). 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 15 Oct 2018.