Neoadjuvant TDM1 With Lapatinib and Abraxane Compared With Trastuzumab Plus Pertuzumab With Paclitaxel
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: T-DM1; Trastuzumab; Lapatinib; Abraxane; Paclitaxel; Pertuzumab
Intervention description: antibody-drug conjugate of trastuzumab and emtansine; anti-Her2 monoclonal antibody; Dual tyrosine kinase inhibitor (HER2 and EGFR); albumin-bound paclitaxel. chemotherapy - microtubule inhibitor.; chemotherapy - microtubule inhibitor; anti-HER2 monoclonal antibody
Intervention MeSH terms: Paclitaxel; Ado-Trastuzumab Emtansine; Albumin-Bound Paclitaxel; Trastuzumab; Pertuzumab; Lapatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 32.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Neoadjuvant Breast Cancer; HER2 positive Breast Cancer

Summary:

      This is a randomized, open label Phase II neoadjuvant study comparing the efficacy and safety
      of trastuzumab emtansine (T-DM1) plus lapatinib (L)followed by abraxane (A) versus
      trastuzumab plus pertuzumab followed by paclitaxel in patients with HER2-overexpressing
      breast cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Female gender;

          -  Age ≥18 years;

          -  Performance Status- Eastern Cooperative Oncology Group (ECOG) 0-1

          -  Histologically confirmed invasive breast cancer:

          -  Primary tumor greater than 1 cm diameter, measured by clinical examination and
             mammography or ultrasound.

          -  Any N,

          -  No evidence of metastasis (M0) (isolated supra-clavicular node involvement allowed);

          -  Over expression and/or amplification of HER2 in the invasive component of the primary
             tumor and confirmed by a certified laboratory prior to randomization.

          -  Known hormone receptor status.

          -  Hematopoietic status:

          -  CBC not less than .75 of institutional lower limit. Absolute neutrophil count ≥ 1,5 x
             10^9/L, Platelet count ≥ 100 x 10^9/L, Hemoglobin at least 9 g/dl,

          -  Hepatic status:

        Serum total bilirubin ≤ 2 x upper limit of normal (ULN). In the case of known Gilbert's
        syndrome, a higher serum total bilirubin (< 1.5 x ULN) is allowed, Aspartate
        Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 3.5 times ULN, Alkaline
        phosphatase ≤ 2.5 times ULN, • Renal status: Creatinine ≤ 1.5mg/dL,

        • Cardiovascular: Baseline left ventricular ejection fraction (LVEF) ³ ≥50% measured by
        echocardiography (ECHO) or Multiple Gate Acquisition (MUGA) scan,

          -  Negative serum or urine β-hCG pregnancy test at screening for patients of childbearing
             potential within 2-weeks (preferably 7 days) prior to randomization.

          -  Fertile patients must use effective contraception (barrier method - condoms, diaphragm
             - also in conjunction with spermicidal jelly, or total abstinence. Oral, injectable,
             or implant hormonal contraceptives are not allowed)

          -  Signed informed consent form (ICF)

          -  Patient accepts to make available tumor samples for submission to central laboratory
             to conduct translational studies as part of this protocol.

        Exclusion Criteria:

          -  Previous (less than 5 years) or current history of malignant neoplasms, except for
             curatively treated: Basal and squamous cell carcinoma of the skin; Carcinoma in situ
             of the cervix.

          -  Patients with a prior malignancy diagnosed more than 5 years prior to randomization
             may enter the study.

          -  Preexisting peripheral neuropathy ≥ grade 2

          -  Known history of uncontrolled or symptomatic angina, clinically significant
             arrhythmias, congestive heart failure, transmural myocardial infarction, uncontrolled
             hypertension (≥180/110), unstable diabetes mellitus, dyspnea at rest, or chronic
             therapy with oxygen;

          -  Concurrent disease or condition that would make the subject inappropriate for study
             participation or any serious medical disorder that would interfere with the subject's
             safety;

          -  Unresolved or unstable, serious adverse events from prior administration of another
             investigational drug;

          -  Dementia, altered mental status, or any psychiatric condition that would prevent the
             understanding or rendering of ICF;

          -  Malabsorption syndrome, disease significantly affecting gastrointestinal function, or
             resection of the stomach or small bowel. Subjects with ulcerative colitis are also
             excluded;

          -  Concurrent neoadjuvant cancer therapy (chemotherapy, radiation therapy, immunotherapy,
             biologic therapy other than the trial therapies);

          -  Concurrent treatment with an investigational agent or participation in another
             therapeutic clinical trial;

          -  Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
             chemically related to trastuzumab Emtansine, trastuzumab, lapatinib, paclitaxel,
             abraxane or their components;

          -  Pregnant or lactating women;

          -  Concomitant use of CYP3A4 inhibitors or inducers

          -  Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g.
             active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable
             safety risks or compromise compliance with the protocol

          -  Patients have an active infection and require IV or oral antibiotics.

          -  Pregnant or breast-feeding women

          -  Patients unwilling or unable to comply with the protocol