NCI Community Oncology Research Program - Protocol Summary
Alliance A011106 - "Alternate Approaches for Clinical Stage II or III Estrogen Receptor Positive Breast Cancer NeoAdjuvant Treatment (ALTERNATE) in Postmenopausal Women"
The summary below serves as a brief review of the treatment plan and eligibility for the protocol.
This summary is not intended to be used in place of the full eligibility & treatment information in the protocol.
Please contact KCCOP for complete protocol information.
Breast Clinical Trial
CANCER TYPE: Stage III
RESEARCH BASE: Alliance A011106
NCT NUMBER: 01953588
HIPPA FORM: DOWNLOAD HIPPA FORM
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Neoadj., T2-T4 any N M0, ER+, post-menopausal; Anastrozole vs Fulvestrant vs both ---> Surgery ---> Endocrine therapy x 4.5 yrs (dependent on Modified PEPI score). DCP-001 Eligible
Treatment Plan (Supplied Drug: Fulvestrant)
FIRST PHASE (RANDOMIZED NEO-ADJUVANT COMPARISON PHASE) - 1st 400 pts
PRE-TX CORE BX & CLIP PLACEMENT (required)
Arm 1 - Anastrozole: QD x 6 cycles, followed by surgery
Arm 2- Fulvestrant: Days 1 & 15 of Cycle 1 and Day 1 of Cycles 2-6, followed by surgery
Arm 3 - Anastrozole: QD and Fulvestrant: Days 1 & 15 of Cycle 1 and Day 1 of Cycles 2-6, followed by surgery
SURGERY (required tumor bx)
If Modified PEPI Score = 0*, adjuv chemo is NOT recommended.
Arm 1 will continue w/Anastrozole x 4.5 yrs
Arm 2 will continue w/Fulvestrant x 1.5 yrs, then Anastrozole x 3 yrs
Arm 3 will continue w/Anastrozole + Fulvestrant x 1.5 yrs, then Anastrozole alone x 3 yrs
If Modified PEPI Score >0*, proceed w/adjuv chemo followed by endocrine therapy (both of investigator's choice).
* Calculated by registering investigator (§15.1.2).
ALL ARMS - 4-wk required bx & 12-wk optional bx
If pt is found at either bx to have endocrine-resistant disease (Ki67 >10%), neoadjuv endocrine therapy will be DC'd. Recommended that pt be switched to 12 wks of neoadjuv Paclitaxel (the Neoadjuv Chemo Group) or another regimen of investigator's choice containing taxane &/or anthracycline or CMF regimen administered per NCCN guidelines.
Cycle 1 Day 2 optional bx (only pts receiving Paclitaxel)
SURGERY (required tumor bx)
Adjuv therapy of investigator's choice
SECOND PHASE (MODIFIED PEPI 0 VALIDATION PHASE) - Between the completion of randomization to the First Phase and the analysis of endocrine resistance data, all pts will be enrolled to Arm 1. Based on the analysis, one or both of the other Arms may be open to enrollment.
- Female, age >18.
- ECOG perf status 0-2.
- Post-menopausal (see protocol definition).
- Path-confirmed invasive breast cancer by core needle bx.
- Clinical T2-T4c, any N, M0 invasive breast cancer, by AJCC 7th edition clinical staging, with the goal being surgery to complete excision of the tumor in the breast and the lymph node. Primary tumor must be:
- its largest diameter is > 2.0 cm by physical examination or by radiological assessment
- Patients with contralateral ductal carcinoma in situ and/or invasive breast cancer are not eligible.
- Patients with multi-centric breast cancer (defined as more than one lesion of invasive breast cancer in the same breast separated by > 2 cm of normal breast tissue are not eligible.
- Clinical T2-T4c, any N, M0 (AJCC 7th ed.). Goal is to completely excise tumor in the breast & lymph node(s). Disease extent is a solitary lesion that is 1) palpable, 2) can be bidimensionally meas by tape, ruler, or caliper, & 3) largest tumor diameter >2.0cm. Contralateral DCIS &/or invasive breast cancer is not allowed. Multifocal/Multilesional breast cancer is not allowed if >1 lesion is invasive breast cancer in same breast.
- ER+ w/Allred score 6, 7, or 8 by local institution standard protocol (or ER+ in >66% cells if Allred not reported). If ER+ is <66%, the staining intensity is needed to calculate the Allred score.
- Invasive breast cancer is HER2 negative. A patient is considered to have HER2 negative breast cancer if one of the following if one of the following applies:
- 0 or 1+ by IHC and ISH not done.
- 0 or 1+ by IHC or ISH ratio (HER2 gene copy/chromosome 17) < 2
- 2+ by IHC and ISH ratio (HER2 gene copy/chromosome 17) < 2
- Documentation of mammogram and ultrasound (including DCIS and invasive cancer) of the diseased breast performed within 56 days prior to registration. Mammogram for the unaffected contralateral breast is required within 12 months prior to registration.
- <14 days pre-regist: ANC >1,000/mm3; platelets >100,000/mm3; total bili <1.5x ULN; creat <1.5x ULN; serum SGOT <2.5x ULN.
- Must agree to provide required research bxs at baseline, Wk 4, & surgery for biomarker & correlative studies.
- No inflammatory breast cancer (clinically significant erythema of breast &/or documented dermal lymphatic invasion).
- No excisional bx of this breast cancer.
- No HRT of any type, megestrol acetate, or Raloxifene w/i 1 wk pre-regist.
- No surgical axillary staging pre-study entry. FNA or core needle bx of axillary node is allowed.
- No clinical or radiographic evidence of mets. Mets workup is not required, but is recommended if Stg III disease. Isolated ipsilateral supraclavicular node involvement is permitted.
- Breast implants are contraindicated only if implant precludes the required research bxs. Pts w/implants removed w/i 6 wks pre-regist are allowed.
- No tx for this cancer pre-study entry.
- No prior invasive breast cancer or contralateral DCIS.
- PRE-STUDY REQUIREMENTS:
- H&P, ht, wt, perf status*
- Clinical msmts of breast lesions**
- CBC/diff/platelets, PT/INR, serum creat, SGPT, total bili*
- Mammogram & US of breast & axillary masses (w/i 42 days pre-regist; include bidimensional tumor msmts)***
- Tumor bxs (MANDATORY; contact KCCOP for kit)#
- Research blood samples (w/pt's consent)
- Signed informed consent.
* <14 days prre-regist.
** Use standard cm-calibrated caliper, measuring tape, or ruler. Both longest & perpendicular axis of tumor. <14 days prior to initiation of study therapy.
*** Mammogram of contralateral breast <12 mos pre-regist unless mastectomy performed.
# Preferably harvest during US-guided clip placement. See §7.1 for instructions. Ship FedEx overnight (Mon-Thurs only) to Mark Watson, MD, PhD; Alliance Biorepository at Washington Univ.; St. Louis, MO.