1303GCC: Trastuzmab & Pertuzumab With Hormonal Therapy or Chemotherapy in Women Aged 60 and Over.
Condition: Metastatic Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Trastuzumab plus Pertuzumab; Hormonal Therapy with Anastrozole and Fulvestrant; Chemotherapy with Eribulin
Intervention description: Anastrozole 1mg by mouth daily FULVESTRANT 500mg i.m. D1, D15, D28 then every 28-30 days
Intervention MeSH terms: Trastuzumab; Pertuzumab; Fulvestrant; Anastrozole
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: Female
Minimum age: 60 Years
Healthy volunteers: No
Keywords: HER2 overexpressed; Metastatic Breast Cancer; Elderly

Summary:

      This is a phase II study that combines Trastuzumab with Pertuzumab to see how it works in
      women age greater than 60 who have been diagnosed with HER2/neu overexpressed locally
      advanced and/or metastatic breast carcinoma.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Women ≥60 Years of Age.

          2. Histologically confirmed, locally advanced (T4 primary tumor and stage IIIB or IIIC
             disease) or metastatic breast cancer that progressed after treatment with standard
             treatment regimens in the adjuvant or neoadjuvant setting.

          3. Prior treatment with trastuzumab and/or lapatinib in the neo-adjuvant or adjuvant
             setting is allowed but not required. Lapatininb has to be discontinued > 21 days
             before the initiation of the T+P study treatments.

          4. Up to 3 prior chemo regimens for treatment of metastatic disease are allowed as long
             as the study subject is acceptable for study treatment with chemo required on this
             study in cohort 2 at progression on T+P.

          5. Patients may have had prior hormonal therapy with any hormonal agents as per section
             3.1.5 of this protocol.

          6. Zometa or denosumab can be continued as per standard of care as long as started before
             the study treatment is started.

          7. HER2 positive breast cancer, as defined in Section 3.3 of this protocol

          8. Must have measurable or evaluable disease according to RECIST 1.1 criteria.

          9. Lab values obtained ≤7 days prior to registration as indicated in 3.1.9 of this
             protocol.

         10. ECOG Performance Status (PS) of 0, 1 or 2.

         11. LVEF at least 50% as determined by MUGA or ECHO.

         12. Life expectancy >3 months.

         13. Written informed consent.

         14. Willingness to return to study site for treatment and follow-up.

         15. Normal QTc interval defined on EKG as QTc ≤ 440 msec.

         16. Postmenopausal women defined in section 3.1.16 of this protocol.

        Exclusion Criteria:

          1. Stage III or IV cancer, other than breast cancer, in ≤5 years prior to registration.

          2. Actively being treated for other malignancy.

          3. New York Heart Association Class III or IV cardiovascular disease.

          4. History of coronary heart failure (CHF)

          5. Current use of drugs known to prolong the QTc interval including Class Ia and III
             antiarrhythmics or history of congenital long QTc syndrome.

          6. Evidence of active brain metastasis including leptomeningeal involvement.

          7. Major surgery, chemotherapy, hormonal or immunologic therapy ≤3 weeks prior to
             registration.

          8. Radiotherapy ≤3 weeks prior to registration, except if to a non-target lesion only.

          9. Prior treatment with Pertuzumab, Eribulin, Fulvestrant or Anastrozole.

         10. Uncontrolled illness.

         11. Co-morbid systemic illnesses or other severe concurrent disease. See section 3.2.11.

         12. Currently receiving treatment in a different clinical study in which investigational
             procedures are performed or investigational therapies are administered.

         13. Immunocompromised patients (other than that related to the use of corticosteroids)
             including patients known to be HIV positive.

         14. International normalized ratio (INR), activated partial thromboplastin time (aPTT) or
             partial thromboplastin time (PTT) >1.5 × ULN (unless on anticoagulation medication)

         15. Receipt of intravenous (IV) antibiotics for infection within 7 days prior to
             enrollment into the study.

         16. Current chronic daily treatment with corticosteroids. See section 3.2.16 of this
             protocol.

         17. Known hypersensitivity to any of the study treatments or to excipients of recombinant
             human or humanized antibodies.

         18. History of receiving any investigational treatment within 28 days prior to enrollment
             into the study.

         19. Assessed by the investigator to be unable or unwilling to comply with the requirements
             of the protocol.