Clinical trial NCT02658084 (phase 1/phase 2, status: terminated)
Conditions: breast cancer, metastatic breast cancer
ICD codes: C79.81, D24.1, D24.2, D24.9, D49.3, C44.501, D48.60, C79.81, D24.1, D24.2, D24.9, D49.3, C44.501, D48.60
Drugs: vinorelbine, trastuzumab emtansine
SMILES: [H][C@@]12N(C)C3=CC(OC)=C(C=C3[C@@]11CCN3CC=C[C@](CC)([C@@]13[H])[C@@]([H])(OC(C)=O)[C@]2(O)C(=O)OC)[C@]1(C[C@@]2([H])CN(CC(CC)=C2)CC2=C1NC1=CC=CC=C21)C(=O)OC, [H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1
Reason stopped: 
    terminated due to low accrual and toxicity concerns.
  
Eligibility criteria:

        Inclusion Criteria:

          1. Histologically or cytologically documented breast cancer.

          2. Metastatic or unresectable locally advanced/recurrent breast cancer.

          3. HER2-positive disease documented as: Immunohistochemistry (IHC) 3+ positive, and/or
             Fluorescence in situ hybridization (FISH) ≥ 2.0, and/or gene copy number greater than
             6, on previously collected tumor or metastatic site. IHC testing, FISH assay(s), and
             gene copy number may all have been performed; however, a positive result from only one
             of the above is required for eligibility.

          4. Documented disease progression on the last regimen by radiographic measurement
             (progression demonstrated by tumor markers only is unacceptable).

          5. Documented disease progression (by investigator assessment) after at least one regimen
             of HER2-directed therapy in the metastatic or unresectable locally advanced/recurrent
             setting.

          6. For patients with hormone receptor-positive disease: disease progression or recurrence
             in any setting on prior hormonal therapy, given with or without HER2 directed therapy.

          7. Measurable or bone only disease.

          8. Prior treatment with a taxane, in the neoadjuvant, adjuvant, locally advanced or
             metastatic setting.

          9. A minimum of 6 weeks of prior trastuzumab for the treatment of metastatic or
             unresectable locally advanced/recurrent disease is required.

         10. Prior use of Pertuzumab in any setting is permitted (but not required).

         11. Prior use of Lapatinib in any setting is permitted (but not required).

         12. Age ≥ 18 years

         13. Life expectancy ≥ 3 months

         14. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. See Appendix C
             for details.

         15. Patients must have normal organ and marrow function as defined below:

               -  absolute neutrophil count (ANC) >1,500 cells/mm3

               -  platelets >100,000 cells/mm3

               -  hemoglobin > 9.0 g/dL (Patients are permitted to receive transfused red blood
                  cells to achieve this level.)

               -  total bilirubin ≤1.5 X institutional upper limit of normal (ULN) [Note: For
                  patients with previously documented Gilbert's syndrome, total bilirubin ≤ 3
                  mg/dL.]

               -  Aspartate aminotransferase (AST/SGOT) ≤ 2.5 X ULN

               -  Alanine aminotransferase (ALT/SGPT) ≤ 2.5 X ULN

               -  alkaline phosphatase (alk phos) ≤ 2.5 X ULN

               -  serum creatinine < 1.5 X ULN

         16. International normalized ratio (INR) < 1.5 X ULN

         17. Left ventricular ejection fraction (LVEF) ≥ 50% by either echocardiogram (ECHO) or
             multiple-gated acquisition scan (MUGA).

         18. Negative results of serum pregnancy test for premenopausal women of reproductive
             capacity and for women < 12 months after menopause. For men and women of childbearing
             potential, agreement by the patient and/or partner to use two effective non-hormonal
             forms of barrier contraception at the same time, throughout treatment on study. Women
             should agree to continued use for at least 90 days after the end of treatment. Men
             should agree to continued use for at least 7 months after the end of treatment.
             Examples of non-hormonal barrier contraception include: condom or occlusive cap
             (diaphragm or cervical/vault caps) with spermicide.

         19. Ability to understand and willingness to sign a written informed consent and HIPAA
             document.

        Exclusion Criteria:

          1. Chemotherapy ≤21 days prior to first dose of study treatment

          2. If last dose of trastuzumab was:

               -  6mg/kg then ≤21 days prior to first dose of study treatment

               -  4mg/kg then ≤14 days prior to first dose of study treatment

               -  2mg/kg then ≤7 days prior to first dose of study treatment

          3. Lapatinib ≤14 days prior to first dose of study treatment

          4. Pertuzumab ≤21 days prior to first dose of study treatment

          5. Hormone therapy ≤7 days prior to first dose of study treatment

          6. Investigational therapy or any other such experimental therapy ≤28 days prior to first
             dose of study treatment

          7. Prior treatment with trastuzumab emtansine, (on or off a study protocol)

          8. Prior use of vinorelbine (in any setting).

          9. Previous radiotherapy for the treatment of unresectable, locally advanced, recurrent
             or metastatic breast cancer is not allowed if:

               -  The last fraction of radiotherapy has been administered within 14 days prior to
                  study enrollment

               -  More than 25% of marrow-bearing bone has been irradiated

         10. Brain metastases that are untreated or symptomatic, or require any radiation, surgery,
             or continued steroid therapy to control symptoms from brain metastases within 14 days
             of study enrollment.

         11. History of intolerance (including Grade 3 or 4 infusion reaction) or hypersensitivity
             to trastuzumab or murine proteins.

         12. History of exposure to the following cumulative doses of anthracyclines:

               -  Doxorubicin ≥550mg/m2

               -  Liposomal doxorubicin >500 mg/m2

               -  Epirubicin >900 mg/m2

               -  Mitoxantrone > 120 mg/m2

               -  If another anthracycline, or more than one anthracycline, has been used, the
                  cumulative dose must not exceed the equivalent of ≥550 mg/m2 doxorubicin.

         13. Current peripheral neuropathy of Grade ≥3 per the NCI CTCAE, v4.0

         14. The patient has not recovered from any other acute toxicity (to Grade ≤1 as per NCI
             CTCAE v4.03) prior to study enrollment.

         15. History of other malignancy within the last 3 years, except for appropriately treated
             carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer,
             or other cancers with a similar outcome.

         16. Cardiopulmonary Function Criteria:

               -  Current unstable ventricular arrhythmia requiring treatment

               -  History of symptomatic congestive heart failure (CHF) as per New York Heart
                  Association (NYHA) Classes II-IV; see Appendix D for details.

               -  History of myocardial infarction or unstable angina within 6 months of study
                  enrollment

               -  History of a decrease in LVEF to < 40% or symptomatic CHF with previous
                  trastuzumab treatment

               -  Severe dyspnea at rest due to complications of advanced malignancy or requiring
                  current continuous oxygen therapy

         17. Current severe, uncontrolled systemic disease (e.g., clinically significant
             cardiovascular, pulmonary, or metabolic disease)

               -  Major surgical procedure or significant traumatic injury within 28 days -before
                  enrollment or anticipation of the need for major surgery during the course of
                  study treatment

               -  Current pregnancy or lactation

               -  Current known uncontrolled active infection with HIV, hepatitis B, and/or
                  hepatitis C virus

         18. Any uncontrolled, intercurrent illness including but not limited to ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia.

         19. Any other serious medical or psychiatric illness/condition likely in the judgment of
             the Investigator(s) to interfere or limit compliance with study
             requirements/treatment.