CTSU ACOSOG Z1031 - "A Randomized Phase III Trial Comparing 16 to 18 Weeks of Neoadjuvant Exemestane (25mg daily), Letrozole (2.5mg), or Anastrozole (1mg) in Postmenopausal Women with Clinical Stage II and III Estrogen Receptor Positive Breast Cancer"

NOTE:  Cohort A reached its accrual and was closed 8/15/09.

Treatment Plan    (Supplied Drug:  None)

COHORT B

Slide submission (10 unstained Superfrost Plus slides) required for PEPI, ER, & Ki67 testing on ALL pts.  PEPI score calculated only for pts who complete AI therapy.

Arm 1

Exemestane:  25mg/day, PO, x 16-18 wks (followed by surgery)

Arm 2

Letrozole:  2.5mg/day, PO, x 16-18 wks (followed by surgery)

Arm 3

Anastrozole:  1mg/day, PO, x 16-18 wks (followed by surgery)

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BX FOR Ki67 TESTING (AFTER 2-4 WKS OF STUDY TX)

Submit:  2 core bxs, frozen in separate OCT blocks & 2 formalin-fixed core bxs, w/14G core needle - CONTACT KCCOP FOR KIT

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1)  If Ki67 <10:  Continue AI therapy

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SURGERY

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PEPI score 0; Path stage 1/0:  No chemo recommended

PEPI >0; Path stage >1:  Chemo discretionary

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Follow until death or maximum 10 yrs

2)  If Ki67 >10:  Receive chemo or immediate surgery

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SURGERY

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Follow until death or maximum 10 yrs

Eligibility

• ECOG/Zubrod perf status <2.

• Clinically staged T2-T4c, any N, M0 breast cancer.  Prim tumor must be palpable and >2cm by tape, ruler, or caliper in >1 dimension.

• Post-menopausal, verified by:  bilat surgical oophorectomy OR no spontaneous menses >1 yr OR no menses <1 yr w/FSH & estradiol levels in post-menopausal range (by instit standards).

• Clinically staged by operating surgeon as 1 of following:

  • T4 a-c and modified radical mastectomy w/negative margins is goal

  • T2 or T3 and conversion from needing mastectomy to breast conservation is goal

  • T2 and lumpectomy at 1st attempt is goal

• ER+ tumor w/Allred score 6-8.  NOTE:  Pts w/>66.6% (2/3) of cells staining positive have a minimum Allred score of 6 & are eligible.

• Mammogram and ultrasound w/i 42 days pre-regist.

• If pt is a cancer survivor, all of following must be met:

  • Has undergone potentially curative therapy for all prior malignancies

  • No prior malignancies w/i past 5 yrs w/no evidence of recurrence (except successfully treated in situ  cervical carcinoma, in situ  lobular breast carcinoma, contralateral DCIS treated w/mastectomy or lumpectomy & RT but w/o Tamoxifen tx, or non-melanoma skin cancer w/no evidence of recurrence)

  • Low risk for recurrence from prior malignancies (treating physician's opinion)

• No inflammatory breast cancer &/or documented dermal lymphatic invasion.

• No prior tx for invasive breast cancer.  No pts whose dx was established by incisional bx.

• No HRT of any type, megestrol acetate, or raloxifene w/i 1 wk pre-regist.

• No M1, excluding isolated ipsilateral supraclavicular node involvement.

• Must agree to mastectomy or lumpectomy after neoadjuv aromatase inhibitor therapy.

• No enrollment on another neoadjuv clinical trial for tx of existing breast cancer.

• COHORT B ONLY:  No pt who has undergone prior sentinel node bx.

• PRESTUDY REQUIREMENTS:

  • TNM stage, ECOG/Zubrod PS, menopausal status, surgery status, ER+ status by Allred

  • Breast mass msmt (tape, ruler, or caliper - bidimensional msmts required)*

  • Gyn exam w/i 1 yr pre-study regist (if applicable - recommended)

  • Cessation of prohibited meds (1 wk pre-regist & tumor, serum, & plasma harvest) - see protocol list

  • Mammogram/US of breast mass; US of axilla mass (mammogram & US w/bidimensional tumor msmts <42 days pre-regist)

  • Concomitant therapies & meds (No HRT, megestrol acetate, or raloxifene allowed)

  • Biopsies/tissue (stop prohibited meds 1 wk prior)** - CONTACT KCCOP FOR KIT

  • Serum & plasma (stop prohibited meds 1 wk prior)** - CONTACT KCCOP FOR KIT

  *     Pre-regist & prior to study drug (baseline).  Pre-regist msmt may be used in lieu of baseline msmt if obtained w/i 14 day window.

  **   REQUIRED FOR ALL PTS.  BASELINE TISSUE SAMPLES MAY BE COLLECTED AT DIAGNOSTIC BX IF PT HAS SIGNED SUPPLEMENTAL SAMPLE COLLECTION CONSENT FORM.  Z1031 TISSUE ACQUISITION PROCEDURES MUST BE FOLLOWED & SAMPLES STORED APPROPRIATELY w/STANDARD LOCAL PATH IDENTIFIERS.  THEY MAY BE RELEASED TO Z1031 AFTER PT HAS CONSENTED TO Z1031 & HAS BEEN REGISTERED.  Leftover tissue may be submitted for central specimen banking unless pt refuses.

  Tissue:  2 core bxs frozen in separate OCT blocks & 2 core bxs in 10% buffered formalin at baseline (prior to study drug administration)

  Serum/Plasma/Whole Blood:  One 10cc red-top Vacutainer & two 10cc Vacutainers containing EDTA of perip blood at baseline (prior to study drug administration).  Process per protocol.  Freeze serum & plasma in -80^oC freezer (do not use liquid nitrogen).  Do not freeze whole blood. 

  Ship all samples via overnight delivery (send Mon-Fri) to:  Mark Watson, MD, PhD; ACOSOG Central Specimen Bank; Barnes-Jewish Hospital North; St. Louis, MO.  Ship formalin-fixed samples at 15^oC and OCT-embedded tumor, serum, & plasma on dry ice.  

• Signed informed consent & HIPAA.