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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.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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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
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

Other trials in United States

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 groups in NCT00651976
Study groupRoleWhat they receive
treatmentExperimentalNot 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.

  1. 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)
  1. In situ apoptotic effect of letrozole

    Measured by level of capase-3 in post-treatment breast tissue.

    Measured: day 7 to day 21

  2. 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.

  1. First posted3 Apr 2008 (estimated)
  2. Study startMar 2008
  3. Primary completionSep 2018
  4. Study completionSep 2018

Why it stopped: funding unavailable

Resources

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)
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

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.

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