T-DM1+Pertuzumab in Pre-OP Early-Stage HER2+ BRCA
Condition: HER-2 Positive Breast Cancer; Breast Cancer; Stage II Breast Cancer; Stage III Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: T-DM1; Pertuzumab; Excision of tumor/mastectomy
Intervention description: Neoadjuvant treatment is for a total of 18 weeks.; Neoadjuvant treatment is for a total of 18 weeks.; Definitive breast cancer surgery (excision or mastectomy) marks the end of protocol mandated therapy.
Intervention MeSH terms: Pertuzumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 164.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This research study is studying a combination of drugs as a possible treatment for breast
      cancer that has tested positive for a protein called HER2.

      The names of the study interventions involved in this study are:

        -  Trastuzumab emtansine (also called T-DM1)

        -  Pertuzumab
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have HER2-positive Stage II or III histologically confirmed invasive
             carcinoma of the breast. A minimum tumor size of 2 cm determined by physical exam or
             imaging is required.

          -  HER-2 positive, confirmed by central testing (Clarient labs): IHC 3+ and/or FISH
             positive based on one of the three following criteria:

          -  Single-probe average HER2 copy number≥6.0 signals/cell OR

          -  Dual-probe HER2/CEP17 <2.0 with an average HER2 copy number ≥6.0 signals/cell OR

          -  Dual-probe HER2/CEP17 ratio ≥2.0

          -  ER/PR determination is required.

          -  Bilateral breast cancers are allowed if both cancers are HER2-positive.

          -  Patients with multifocal or multicentric disease are eligible as long as one area
             meets eligibility criteria.

          -  Breast imaging should include the ipsilateral axilla. For subjects with a clinically
             negative axilla, a sentinel lymph node biopsy will be performed either before or after
             preoperative therapy at the discretion of the subject's physicians. For subjects with
             a clinically positive axilla, a needle aspiration, core biopsy or SLN procedure will
             be performed to determine the presence of metastatic disease in the lymph nodes.

          -  Men and women (with any menopausal status) ≥ 18 years of age

          -  ECOG performance status 0 or 1

          -  Required laboratory values:

               -  ANC ≥1500/mm3

               -  Hemoglobin ≥ 9 g/dl

               -  Platelets ≥100,000/mm3

               -  Serum creatinine < 1.5 X ULN (institutional)

               -  Total bilirubin ≤ 1.0 X ULN (institutional) For patients with Gilbert syndrome,
                  the direct bilirubin should be within the institutional normal range.

               -  AST and ALT ≤ 1.5x ULN (institutional)

               -  Alkaline phosphatase ≤1.5x ULN (institutional)

          -  Documentation of hepatitis B virus (HBV) and hepatitis C virus (HCV) serologies is
             required: this includes hepatitis B surface antigen (HBsAg) and/or total hepatitis B
             core antibody (HBcAb) in addition to HCV antibody testing.

          -  Only for patients who test positive for hep B/C virus: PTT/INR < ULN (institutional)

          -  Left ventricular ejection fraction (LVEF) ≥ 55%

          -  Premenopausal women must have a negative serum pregnancy test, including women who
             have had a tubal ligation and for women less than 12 months after the onset of
             menopause.

          -  Women of childbearing potential and men with partners of childbearing potential must
             be willing to use one highly effective form of non-hormonal contraception or two
             effective forms of non-hormonal contraception by the patient and/or partner and
             continue its use for the duration of the study treatment and for 7 months after the
             last dose of study treatment.

          -  Potent CYP3A4 inhibitors, such as ketoconazole and erythromycin, should be avoided
             during the study treatment period with T-DM1.

          -  Excessive alcohol intake should be avoided (occasional use is permitted).

          -  Patients with a history of ipsilateral DCIS are eligible.

          -  Patients undergoing breast conservation therapy (i.e. lumpectomy) must not have any
             contraindications to radiation therapy.

          -  Willing and able to sign informed consent.

          -  Willing to provide tissue for research purposes.

        Exclusion Criteria:

          -  Pregnant or nursing women due to the teratogenic potential of the study drugs.

          -  Active, unresolved infection.

          -  Receipt of intravenous antibiotics for infection within 7 days prior to enrollment.

          -  Patients with active liver disease, for example, due to hepatitis B virus, hepatitis C
             virus, autoimmune hepatic disorder, or sclerosing cholangitis.

          -  Uncontrolled hypertension (systolic >180 mm Hg and/or diastolic >100 mm Hg) or
             clinically significant (i.e. active) cardiovascular disease: cerebrovascular
             accident/stroke or myocardial infarction within 6 months prior to first study
             medication, unstable angina, congestive heart failure (CHF) of New York Heart
             Association (NYHA) Grade II or higher, or serious cardiac arrhythmia requiring
             medication.

          -  Significant symptoms (Grade ≥2) peripheral neuropathy.

          -  Other concurrent serious diseases that may interfere with planned treatment, including
             severe pulmonary conditions/illness, uncontrolled infections, uncontrolled diabetes.

          -  Any prior treatment for the current breast cancer, including chemotherapy, hormonal
             therapy, radiation or experimental therapy.