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CTSU NCIC MA.27 - "A Randomized Phase III Trial of Exemestane Versus Anastrozole in Postmenopausal Women With Receptor Positive Primary Breast Cancer"

Treatment Plan    (Supplied Drugs:  Exemestane & Anastrozole)

MANDATORY - Must be eligible for and willing to participate in substudy MA.27D (until the accrual goal is for the substudy is met).

Adjuv chemo & RT are allowed.  Chemo must be completed b/f RT.  RT, if given, may be given b/f or concurrently w/protocol therapy.  If neither chemo nor RT is given, pts must be randomized >3 wks and <3 mos after prim surgery.  Use of Herceptin w/protocol therapy is allowed.

Arm 1

Exemestane:  25mg, PO, QD, x 5 yrs

Arm 2

Anastrozole:  1mg, PO, QD, x 5 yrs

Eligibility

• Completely resected and histol-confirmed invasive breast cancer which was pT1-pT3; pNx, pN0-pN2 (or only when sole basis for this classification is presence of >10 involved axillary nodes, pN3); M0 (AJCC Version 6).  Surg margins clear of invasive carcinoma and DCIS.  Pts w/positive SN bxs must have subsequent axillary dissection.  Negative SN bxs require no more axillary surg.  (Neo-adjuv pts may be included if both cTNM & pTNM meet protocol requirements for TNM classification.)

• Prim tumor must be ER &/or PgR positive (>10fmol/mg protein, or receptor positive by ERICA or PgRICA).

• Post-meno status prior to chemo, by 1 of following:

  • Woman >60 yrs

  • Woman age 45-59 w/spontaneous cessation of menses for >12 mos pre-chemo*

  • Woman age 45-59 w/cessation of menses duration <12 mos or secondary to hysterectomy AND w/FSH level in pre-chemo* in post-meno range (or >34.4 IU/L if instit range is not avail).

  • Woman age 45-59 on HRT who has discontinued HRT at breast cancer dx and has FSH level pre-chemo* in post-meno range (or >34.4 IU/L if instit range is not avail).

  • Bilat oophorectomy

  *     If no chemo, then pre-randomiz.

• Bilat breast cancer allowed only if cancers are synchronous (diagnosed at same time).  One or both tumors need to have receptor positive markers.  One could be negative.  (NOTE:  MA27.D pts must have 1 intact non-cancerous breast, so bilat breast cancer is not allowed.)

• Bilat mammogram w/i 12 mos pre-randomiz (unless initial surgery was total mastectomy; then only mammogram of remaining breast is required).

• Must be negative for mets:

  • Bone scan (Required only if alk phos >2x normal &/or symptoms of mets disease.  A confirmatory xray or other imaging study is required if results from bone scan are questionable.)

  • Abdominal US or CT (Required only if SGOT/SGPT or alk phos is >2x normal unless elevation is in bone fraction.)

  • CXR

• Must be randomized >3 wks and <3 mos after completion of chemo.  (Adjuv chemo & RT is allowable if pt is randomized and study tx begun as soon as recovered sufficiently from this chemo to meet eligibility criteria.  Pts may be randomized and given protocol therapy prior to or during RT if they have met eligibility criteria.)  If no chemo is given, must be enrolled >3 wks and <3 mos after prim surgery.  (Prim surgery = last surg at which histol evidence of invasive or in situ disease was present in path specimen.)  Neo-adjuv pts must be enrolled >3 wks & <3 mos after excisional surgery.

• Minim life expectancy 5 yrs.

• WBC >3.0 x 10⁹/L or granulocytes (polymorphs + bands) >1.5 x 10⁹/L; platelets >100 x 10⁹/L w/i 4 wks pre-randomiz.

• SGOT &/or SGPT & alk phos <2x IULN unless imaging exams have ruled out mets. 

• ECOG perf status 0-2.

• Must be able to swallow study meds and have adequate unassisted oral intake to maintain reasonable nutrition.

• Must be accessible for tx and follow-up.

• Protocol therapy must begin w/i 10 working days of randomiz.

• Must consent to participate in MA.27D (until the accrual goal for the substudy is met).

• Must consent to blood banking (whole blood for DNA analysis; baseline blood sample for MA.27D is shipped at same time for storage).

• No metachronous breast cancer (diagnosed at different times).

• Not eligible if <3 wks or >3 mos have elapsed since completion of chemo (if no chemo, not eligible if <3 wks or >3 mos have lapsed since prim surgery).

• No hx of other (non-breast) malignancies except adequately treated non-melanoma skin cancer, curatively treated in situ  cervical cancer, or other solid tumors curatively treated w/no evidence of disease >5 yrs.

• No concurrent hormonal therapy w/estrogens, progesterones or androgens, or any SERM.  Vaginal atrophy refractory to local measures may be treated at physician's discretion, w/intermittent vaginal estrogens.  (See protocol for details).

• No prior tx w/recognized aromatase inhibitor.

• No co-existing medical or psychiatric condition likely to interfere w/study procedures &/or results.

• No prior tx on a breast cancer trial if permission has not been obtained from the sponsors of the original study.  (MA.20 pts may participate in MA.27.  MA.21 pts may not participate in MA.27.)

• No prior tx w/Tamoxifen or SERMs other than Raloxifene.  (Previous use of Raloxifene in allowed, if pt has been off >3 wks pre-randomiz.)  No prior tx w/hormones or steroids (including OTC products and supplements considered to have an estrogenic effect) unless discontinued >3 wks pre-randomiz.

• No prior or concurrent dx of in situ carcinoma of contralateral breast treated w/partial mastectomy &/or hormonal therapy.  (Pts w/prior or concurrent in situ carcinoma of ipsilateral breast are eligible if completely excised and have not received hormonal therapy).

• PRESTUDY REQUIREMENTS:

  • H&P*

  • Alk phos, calcium, creat, SGOT/SGPT*

  • WBC, granulocytes, platelets, Hgb*

  • FSH (if required for menopausal asmt, perform prior to any chemo)

  • Whole blood sample (5-10ml in purple-top EDTA tube) for banking#%

  • ER/PR status

  • Histology

  • Lymph node status@

  • Bilat mammogram as appropriate (w/i 10 mos pre-randomiz; MRIs may not subsitute for mammograms)$

  • CXR (mandatory) or Chest CT**

  • Bone scan (Only if alk phos >2x normal &/or symptoms of mets disease.  Confirmatory Xray is required if results from bone scan are questionable.)**

  • CT abdomen (required only if SGOT/SGPT or alk phos >2x normal)**

  • Current meds/Indications***

  • Baseline symptoms/Toxicity grading/Intercurrent illness (graded by CTCAE Version 3.0)***

  *    Within 4 wks pre-randomiz

  **    >4 wks prior to prim surgery & no later than date of randomiz

  ***   Within 7 days pre-randomiz

  #      Refrigerate at 40^oF and ship w/i 24 hrs of collection with cool pack to:  CALGB PCO; Ohio State Univ; Columbus, OH (for next day arrival - do not ship on Friday).

  @    Forward copies of original diagnostic surgical path report if available (to initiate tumor block banking).

  %    After randomiz & prior to any study tx

  $     Pt must also consent to future mammogram access

• Signed informed consent.