Goserelin and Letrozole or Anastrozole in Premenopausal Patients With Stage II-III Estrogen Receptor-Positive Breast Cancer

Conditions:Breast Cancer, Cancer, Cancer, Cancer, Cancer, Cancer, Cancer
Therapuetic Areas:Oncology
Age Range:Any
Start Date:July 2011

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A Multisite International Collaborative Phase 2 Study of Neoadjuvant Goserelin and a Non-steroidal Aromatase Inhibitor for Premenopausal Women With Estrogen Receptor Positive HER2 Negative Clinical Stage 2 and 3 Breast Cancer

This phase II trial studies the impact of a presurgical endocrine therapy, consisting of
goserelin with letrozole or anastrozole on the treatment of premenopausal patients with
stage II-III estrogen receptor-positive (ER+) and human epidermal growth factor receptor 2
(HER2)-negative breast cancer. Endocrine therapy reduces the amount of estrogen in the body.
E+ breast cancer require estrogen, so lower levels of estrogen may slow or stop cell growth.
Giving goserelin together with letrozole or anastrozole before surgery may enhance the
effectiveness of, or eliminate the need for, chemotherapy

PRIMARY OBJECTIVES: I. To determine the pathological complete response (CR) rate to
chemotherapy in patients with fully suppressed estradiol levels following 4 weeks of
endocrine therapy, but have high biopsy levels of Ki67, a biomarker for cell proliferation.
II. To determine how many patients choose postoperative treatment that does not include
chemotherapy, in patients with a Preoperative Endocrine Prognostic Index (PEPI)-0 tumor
following neoadjuvant endocrine therapy. SECONDARY OBJECTIVES: I. To correlate
pretreatment fluoro furanyl norprogesterone (FFNP)-positron emission tomography (PET) with
Ki67 status following a 4-week endocrine treatment and with the PEPI score at the time of
definitive surgery. II. To determine the PEPI-0 rate in patients whose estradiol is fully
suppressed (< or = 15 pg/ml) at both 4 weeks and 16 weeks and whose 4 week tumor Ki67 level
is 10% or less. III. To determine the number of patients whose estradiol is not fully
suppressed at either one month or 16 weeks in response to goserelin with letrozole or
anastrozole and to record the management decision in these cases. TERTIARY OBJECTIVES:
I. To conduct comprehensive genomic profiling, including full genome sequencing, of
endocrine therapy responsive and unresponsive tumors (Groups 1 and 2 respectively), both
before and after therapy to determine the biological basis for primary endocrine therapy
resistance. OUTLINE: Premenopausal patients receive endocrine therapy for 4 weeks.
Patients will then be assigned to a treatment arm according to their responses to the
therapy. ARM 1: If estrogen levels and tumor cell growth drop, patients will continue
endocrine therapy for 16-18 weeks until surgery. ARM 2: If estrogen levels drop but tumors
cell do not respond, patients will receive standard chemotherapy until surgery. ARM 3: If
estrogen levels do not drop, patients and attending physicians will choose an appropriate
treatment. Outcomes of these treatments and selection of post surgical therapy will be
examined. All patients will be assessed every 4 weeks for disease progression prior to
having surgery to remove the tumor. After completion of study treatment, patients are
followed up every 6 months for 5 years and then annually for 5 additional years.

Inclusion Criteria:

- Patient must have histological or cytological confirmed invasive breast cancer

- Patient must be premenopausal confirmed by serum estradiol level in the premenopausal
range (> 25 pg/ml) at the beginning of the study; for women on oral contraceptives,
these agents must be held for two weeks before the estradiol assessment is made

- Patient must have a negative serum pregnancy test within 7 days of registration

- Patient's tumor must be ER+ with or without concomitant progesterone
receptor-positive (PR+) with an Allred score of 6, 7 or 8; patients with > 66.6% of
cells staining positive by conventional immunohistochemistry (IHC) have a minimum
Allred score of 6 and are eligible

- Patient's tumors must be HER2 negative by local laboratory assessment: HER2 IHC 0,
1+, or 2+ with subsequent negative fluorescent in situ hybridization (FISH) (ratio <
1.8); negative FISH alone in absence of IHC is acceptable

- Patient must have T2-T4c, any N, M0 breast cancer, by clinical staging (physical

- Patient's primary tumor must be palpable and measure > 2 cm by tape, ruler or caliper
measurements in at least one dimension

- Patient must have mammogram and ultrasound of the breast within 42 days prior to
registration; if a patient has clinically palpable or suspicious nodes, then an
ultrasound of the axilla is also required

- Patient, as documented by the treating physician, must be clinically staged as one of
the following:

- T4 a-c for which modified radical mastectomy with negative margins is the goal

- T2 or T3 for which conversion from needing mastectomy to breast conservation is the

- T2 for which lumpectomy at first attempt is the goal

- Patient must be > or = 18 years old.

- Patient must stop taking all forms of hormonal treatment, including oral or other
form of hormonal contraceptive methods and all forms of hormone replacement therapy,
at least two weeks prior to starting protocol therapy

- Patient must agree to use a "highly-effective form of non-hormonal contraception"
(applies to patient and/or partner)

- Patient must be willing to undergo oophorectomy, if indicated

- Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of
=< 2

- Patient must have normal organ and marrow function as defined below:

- Leukocytes >= 3,000/mcL

- Absolute neutrophil count >= 1,500/mcL

- Platelets >= 100,000/mcL

- Total bilirubin within normal institutional limits

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT])
=< 3.0 X institutional upper limit of normal (ULN)

- Creatinine within normal institutional limits OR

- Creatinine clearance >= 60 mL/min/1.73 m2 for patients with creatinine levels above
institutional normal

- If the patient is a cancer survivor, all of the following criteria must be met

- Patient has undergone potentially curative therapy from all prior malignancies

- Patient must have no evidence of any prior malignancies for at least 5 years with no
evidence of recurrence (except for successfully treated cervical carcinoma in situ,
lobular carcinoma in situ of the breast, contralateral ductal carcinoma in situ
(DCIS) treated with mastectomy or lumpectomy and radiation but without tamoxifen
treatment, or non-melanoma skin cancer with no evidence of recurrence)

- Patient must be deemed by her treating physician to be at low risk (< 30%) for
recurrence from prior malignancies

- Patient must be able to understand and willing to sign a written informed consent

Exclusion Criteria:

- Patient must not have inflammatory breast cancer defined as clinically significant
erythema of the breast and/or documented dermal lymphatic invasion (not direct skin
invasion by tumor or peau d'orange without erythema)

- Patient must not have had prior treatment for invasive breast cancer, including
radiation, endocrine therapy, chemotherapy, or investigational agent; patients whose
diagnosis was established by incision biopsy are not eligible

- Patient must not have had prior DCIS in the ipsilateral breast

- Patient must not have used tamoxifen for prior contralateral DCIS

- Patient must not have any evidence of distant metastasis (M1) on imaging; staging
scans are not mandatory but any exams performed as standard of care throughout the
study period will be collected for correlation as needed

- If patient does not agree to undergo mastectomy or lumpectomy after neoadjuvant
therapy, she is ineligible for this study

- Patient must not be receiving other investigational agents or be enrolled in another
neoadjuvant clinical trial for treatment of the existing breast cancer

- Pregnant and/or breastfeeding women are excluded from this study

- Patient must not have any concurrent life threatening illnesses

- Patient must not have undergone prior sentinel lymph node surgery; cores or FNA of
lymph node are acceptable
We found this trial at
660 S Euclid Ave
Saint Louis, Missouri 63110
(314) 362-5000
Washington University School of Medicine Washington University Physicians is the clinical practice of the School...
Saint Louis, MO
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