Clinical trial NCT00651976: Letrozole in Treating Postmenopausal Women With Stage I, II or III Breast Cancer That Can Be Removed by Surgery
Official title: Pre-Surgical Trial of Letrozole in Post-Menopausal Patients With Operable Hormone-Sensitive Breast Cancer (Spore)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: EARLY_PHASE1
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
Lead sponsor: Vanderbilt-Ingram Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2008-04-03
Enrollment: 213
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Ki67 index measured in hormone receptor-positive breast cancers compared to those that are hormone receptor-negative
timeFrame: day 7 to day 21
Secondary outcomes:
measure: In situ apoptotic effect of letrozole
timeFrame: day 7 to day 21
measure: Identification of a recurrence risk biomarker profile using RNA microarray
timeFrame: day 7 to day 21
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Tulsa
country: United States
facility: Surgical Associates, Inc.
state: Oklahoma
city: Pittsburgh
country: United States
facility: Allegheny Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center, One Hundred Oaks
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
Study officials:
affiliation: Vanderbilt-Ingram Cancer Center
name: Ingrid Meszoely, MD
role: PRINCIPAL_INVESTIGATOR
References: