Secondary BRain Metastases Prevention After Isolated Intracranial Progression on Trastuzumab/Pertuzumab or T-DM1 in Patients With aDvanced Human Epidermal Growth Factor Receptor 2+ brEast Cancer With the Addition of Tucatinib

Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.

Age ≥ 18 years at the time of consent.

Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.

Locally advanced/unresectable or metastatic breast cancer with presence of brain metastases (Stage IV).

Histologically confirmed HER2+ breast carcinoma by ASCO-CAP guidelines, with HER2+ defined by in situ hybridization (ISH), immunohistochemistry (IHC), or fluorescence in situ hybridization (FISH) methodology on most recent biopsy (primary tissue).

Currently receiving: (1) first-line trastuzumab/pertuzumab with or without endocrine therapy OR (2) second-line T-DM1 in the metastatic setting OR (3) adjuvant trastuzumab-based therapy or T-DM1 with isolated intracranial recurrence. Patients with de novo metastatic disease and brain metastases or isolated metastatic disease to the brain can enroll at time of initiation of trastuzumab/pertuzumab. Induction taxane therapy is not required and need to administer can be determined by the treating physician. Patients on trastuzumab alone are allowed if pertuzumab not tolerated.

Systemic disease otherwise stable per RECIST 1.1 or no evidence of extracranial disease.

Adequate hepatic and renal function and hematologic parameters:

* Absolute neutrophil count (ANC) ≥ 1.0 × 109/L

* Platelets ≥ 100 × 109/L

* Hemoglobin ≥ 9 g/dL

* Total serum bilirubin ≤ 1.5 times upper limit of normal (ULN)

* Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤ 2.5 × ULN (or ≤ 5 × ULN if liver metastases are present)

* Serum creatinine ≤ 1.5 x ULN or estimated creatinine clearance ≥ 50 mL/min as calculated using the Cockcroft-Gault (CG) equation

* Left ventricular ejection fraction (LVEF) ≥ 50%.

Central nervous system inclusion - Based on screening brain magnetic resonance imaging (MRI), patients must have ALL of the following:

* Adequate local therapy to existing brain lesions ≥ 5mm including surgical resection and/or stereotactic radiosurgery

* Limited to first or second intracranial progression. Third intracranial progression would be considered if \> 12 month interval between second and third intracranial progression.

* Time since stereotactic radiosurgery (SRS) is ≥ 7 days prior to first dose of study treatment.

* Time since surgical resection is ≥ 14 days prior to first dose of study treatment.

* Time since local therapy \< 12 weeks. Patients with de novo metastastic breast cancer presenting with brain metastases may enter following cessation of chemotherapy if within 24 weeks of local therapy to the brain and brain metastases have remained stable based on brain MRI.

* Prior radiation is required within 12 weeks of enrollment to at least 1 brain lesion. Other brain lesions under 5mm do not require treatment.

NOTE: Relevant records of any CNS treatment including radiation must be available to allow for classification of target and non-target lesions

Females of childbearing potential must have a negative serum pregnancy test at screening. If a urine test is done and it is positive or cannot be confirmed as negative, a serum pregnancy test will be required. NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months.

Females of childbearing potential and males must be willing to abstain from heterosexual intercourse or to use contraception as outlined in the protocol.

What this study is about