Protocol: NSABP-FB-12

Schema – NSABP-FB-12

Please Note: Below is partial eligibility, for full eligibility requirement’s, please contact GHCI Research Department at (810) 762-8181, (810) 762-8079 and/or (810) 762-8038. Thank you!

Patient Guidelines:

1. Medical oncologist has indicated the intention to administer doxorubicin/cyclophosphamide followed by paclitaxel.
2. Co-morbid conditions should be taken into consideration, but not the diagnosis of breast cancer.
3. All patients will be required to have a research core biopsy procedure to procure fresh tumor tissue for pre-entry central HER2 signaling testing by Celcuity

Eligibility:

1. Patients must be female.
2. Patients must be ≥ 18 years old.
3. Patient must have an ECOG performance status of 0 or 1.
4. The diagnosis of invasive adenocarcinoma of the breast must have been made by core needle biopsy.
5. The primary breast tumor must be palpable and measure ≥ 2.0 cm on physical exam.
6. The regional lymph nodes can be cN0, cN1, or cN2a.
7. Histological grade II or III tumor.
8. Ipsilateral axillary lymph nodes must be evaluated by imaging (mammogram, ultrasound, and/or MRI) within 6 weeks prior to initiating chemotherapy. If suspicious or abnormal, FNA or core biopsy is recommended, also within 6 weeks prior to initiating chemotherapy. Findings of these evaluations will be used to determine the nodal status prior to initiating chemotherapy.
9. Tumor specimen obtained at the time of diagnosis must have ER and PgR analysis assessed by current ASCO/CAP Guidelines. Patients are eligible with either hormone receptor-positive or hormone receptor-negative tumors. Tumor specimen obtained at the time of diagnosis must have been determined to be HER2-negative.

Ineligibility:

1. T4 tumors including inflammatory breast cancer.
2. FNA alone to diagnose the breast cancer.
3. Excisional biopsy or lumpectomy performed prior to initiating chemotherapy.
4. Surgical axillary staging procedure prior to initiating chemotherapy. Pre-neoadjuvant therapy sentinel node biopsy is not permitted. (FNA or core biopsy is acceptable.)
5. Definitive clinical or radiologic evidence of metastatic disease. Required imaging studies must have been performed within 6 weeks prior to initiating chemotherapy.
6. Synchronous bilateral invasive breast cancer. (Patients with synchronous and/or previous contralateral DCIS or LCIS are eligible.)
7. Any previous history of ipsilateral invasive breast cancer or ipsilateral DCIS. (Patients with synchronous or previous ipsilateral LCIS are eligible.)
8. Previous therapy with anthracycline, taxanes, trastuzumab, or other HER2 targeted therapies for any malignancy.
9. History of non-breast malignancies (except for in situ cancers treated only by local excision and basal cell and squamous cell carcinomas of the skin) within 2 years prior to initiating chemotherapy.

Protocol: Alliance – A011801

Schema – A011801

Please Note: Below is a partial list of eligibility, please contact GHCI Research Department at (810)762-8181, (810)762-8079, (810)762-8038 to discuss full eligibility requirements.

ELIGIBILITY:

1. HER2-positive breast cancer, will be based on pre-treatment biopsy material and defined as an immunohistochemistry (IHC) score of 3+ and/or positive by in situ hybridization (ISH) according to current ASCO/CAP guidelines.  Central testing is not required.
2. Known hormone receptor (HR) status as defined by ASCO/CAP guidelines (based on pre-treatment biopsy material). Hormone receptor positive status can be determined by either known positive ER or known positive PR status; hormone receptor negative status must be determined by both known negative ER and known negative PR.
3. Patients with clinical Stage T1-4, N0-3 disease at presentation and residual invasive disease post-operatively as defined about are eligible. (Note: Patients with T1a/bN0 tumors at initial breast cancer diagnosis are not eligible).
4. Patients with residual HR-negative, HER2+ disease in the breast and/or lymph n odes per the surgical pathology report are eligible; however, patients with HR+ HER2+ cancers must have node-positive residual disease per the surgical pathology report in order to qualify for the study. The presence of residual invasive disease in the breast is not mandatory for these patients.
5. Patients with weakly ER-positive (1-10%) breast cancer (based on the pre-treatment core biopsy) are eligible even if they have node negative disease per the surgical pathology report.
6. The residual disease tissue (breast and/or lymph nodes) is not required to be HER2+, as eligibility for this study it is based on a positive HER2 status at the time of the initial breast cancer diagnosis.  Note: The presence of micrometastases in lymph  nodes after pre-operative therapy counts as residual disease, whereas the presence of isolated tumor cells does not.
7. Patients with synchronous bilateral invasive disease are eligible provided both lesions were confirmed to be HER2+ and at least one of the lesions meets the criteria outlined above.  Multifocal disease is allowed, as long as the largest biopsied breast tumor was HER2+.
8. Patients must have received neo-adjuvant chemotherapy with one of the following regimens: THP, TMP, AC-TH(P), TCH(P), FAC-TH(P), or FEC-TH(P).  Note: Apart from TCHP, where T is docetaxel, treatment with docetaxel or paclitaxel is acceptable.
9. Prior receipt of T-DM1 in the neo-adjuvant setting is not allowed.
10. Prior treatment must have consisted of equal to or greater than 6 cycles of chemotherapy and HER2- directed therapy, with a total duration of equal to or greater than 12 weeks, including at least 9 weeks of pre-operative taxane and trastuzuamb with or without pertuzumab (or FDA approved biosimilars). Patients who have received at least 9 weeks of pre-operative taxane, pertuzumab and margetuximab are also eligible if they received equal to or greater than 6 cycles of systemic therapy prior to registration. Note: Patients who complete at least nine of a planned twelve doses of weekly paclitaxel or three of a planned four doses of docetaxel but discontinue prematurely due to toxicity are eligible. Prior use of nab-paclitaxel (Abraxane) instead of paclitaxel or docetaxel is permitted. Prior use of subcutaneous trastuzumab (Hylecta) and subcutaneous trastuzumab and pertuzumab (Phesgo) is also allowed.
11. Patients who received neo-adjuvant systemic therapy which included experimental HER2- targeted therapy/therapies are potentially eligible, as long as the investigational agent was not a HER2-targeted antibody drug conjugate (e.g. T-DM1 or trastuzumab deruxtecan) or a HER2 targeted tyrosine kinase inhibitor (e.g. tucatinib, lapatinib, neratinib).
12. No adjuvant treatment with any anti-cancer investigational drug within 28 days prior to registration.
13. Patients may have received equal to or greater than 1 cycle of T-DM1 in the adjuvant setting.  Note: These patients will be randomized to receive a further 14 cycles of T-DM1 and tucatinib/placebo as tolerated. The most recent cycle of T-DM1 should have been administered equal to or greater than 5 weeks prior to registration.
14. All systemic chemotherapy should have been completed pre-operatively unless participating in EA1181 (CompassHER@ pCR) or the BIG DECRESCENDO Trial. However, patients who received 4 cycles of neo-adjuvant THP off study can receive a further 2-4 cycles of chemotherapy post-operatively to meet eligibility for A011801/
15. Toxicities related to prior systemic treatment should have resolved or be at baseline, apart from alopecia and peripheral neuropathy less than or equal to 1.
16. Adequate excision: surgical removal of all clinically evident disease in the breast and lymph nodes.
17. Breast Surgery: Total mastectomy with no gross residual disease at the margin of resection or breast conserving surgery with histologically negative margins of excision. For patients who undergo breast conserving surgery, the margins of the resected specimen must be histologically free of invasive tumor and ductal carcinoma in situ (DCIS) as determined by the local pathologist.  If pathologic examination demonstrates tumor at the line of resection, additional operative procedures may be performed to obtain clear margins. If tumor is still present at the resected margin after re-excision the patient must undergo total mastectomy to be eligible. Patients with margins positive for classic lobular carcinoma in situ (LCIS) are eligible without additional resection.
18. Lymph node surgery: The axilla needs to be evaluated with either sentinel node biopsy or axillary lymph node dissection. If patients have a sentinel lymph node biopsy and sentinel nodes are negative, no further axillary treatment is necessary.  If patients have isolated tumor cells in the sitting of residual breast disease, at least one of the following is required: ALND or planned nodal irradiation to the level I/II axilla. If patients have micro- or macro-metastatic nodal disease, ALND and planned nodal irradiation are required. Of note, co-enrollment on Alliance A011202 is not allowed.