Clinical trial NCT00903006 (phase 1/phase 2, status: terminated)
Conditions: breast cancer
ICD codes: C79.81, D24.1, D24.2, D24.9, D49.3, C44.501, D48.60
Drugs: fulvestrant, mk-0646, dasatinib
SMILES: [H][C@@]12CC[C@H](O)[C@@]1(C)CC[C@]1([H])C3=CC=C(O)C=C3C[C@@H](CCCCCCCCCS(=O)CCCC(F)(F)C(F)(F)F)[C@@]21[H], [H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1, CC1=NC(NC2=NC=C(S2)C(=O)NC2=C(C)C=CC=C2Cl)=CC(=N1)N1CCN(CCO)CC1
Reason stopped: 
    low accrual
  
Eligibility criteria:

        Inclusion Criteria:

          1. For the Phase I: Patients with histologically or cytologically confirmed diagnosis of
             metastatic hormone receptor-positive HER2-negative breast cancer who have received up
             to one line of endocrine therapy for metastatic disease.

          2. Measurable disease by Response Evaluation Criteria In Solid Tumors (RECIST) or
             evaluable disease (e.g., bone metastasis, or lesions which do not fulfill RECIST
             criteria for metastatic disease)

          3. Age >/= 18 years

          4. Eastern Cooperative Oncology Group (ECOG) performance status of </= 2

          5. Required laboratory values: Absolute neutrophil count (ANC)>/= 1500 cells/mm^3,
             platelet count >/= 100,000 cells/mm^3, hemoglobin >/= 9 gm/L; bilirubin </= 1.5 *
             upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate
             aminotransferase (AST) </= 2.5 * ULN; serum creatinine </= 2.0 * ULN

          6. Ability to understand the requirements of the study, provided written informed consent
             and authorization of use and disclosure of protected health information, and agree to
             abide by the study restrictions and to return for the required assessments.

          7. Patients must be postmenopausal (> 12 months of amenorrhea, bilateral oophorectomy).

          8. Patients must have received prior anti-estrogen therapy in the adjuvant setting.

          9. Patients may have easily accessible tumors for biopsy (confirmed by interventional
             radiology).

         10. Patients must consent to biopsies.

         11. For the Phase II: Patients with histologically or cytologically confirmed diagnosis of
             metastatic hormone receptor-positive, HER2-negative, breast cancer who have received
             up to one line of endocrine therapy for metastatic disease.

         12. Measurable disease by RECIST or evaluable disease (e.g., bone metastasis, or lesions
             which do not fulfill RECIST criteria for metastatic disease)

         13. Age >/= 18 years

         14. ECOG performance status of </= 2

         15. Required Laboratory Values: ANC >/= 1500 cells/mm^3, platelet count >/= 100,000
             cells/mm^3, hemoglobin >/= 9 gm/L, Bilirubin </= 1.5 * ULN, alanine aminotransferase
             (ALT) and aspartate aminotransferase (AST) </= 2.5 * ULN

         16. Serum creatinine </= 2.0 * ULN

         17. Ability to understand the requirements of the study, provide written informed consent
             and authorization of use and disclosure of protected health information, and agree to
             abide by the study restrictions and to return for the required assessments.

         18. Patients must be postmenopausal (> 12 months of amenorrhea, bilateral oophorectomy).

         19. Patients must have received prior anti-estrogen therapy in the adjuvant setting.

         20. Patients may have easily accessible tumors for biopsy (confirmed by interventional
             radiology).

         21. Patients must consent to biopsies.

        Exclusion Criteria:

          1. For the Phase I: History of prior malignancies within the past 5 years with the
             exception of curatively treated basal or squamous cell carcinomas of the skin or
             carcinoma in situ of the cervix

          2. Concurrent severe or uncontrolled medical disease (i.e., systemic infection, diabetes,
             hypertension, coronary artery disease, congestive heart failure, ongoing or recent
             gastrointestinal bleed, hepatic or cardiac compromise, hypocalcemia, or known platelet
             function abnormality).

          3. Concomitant medication known to prolong QT interval, unless discontinued >/= 7 days of
             starting dasatinib therapy.

          4. Newly diagnosed (within 3 months before enrollment) or poorly controlled (defined as a
             fasting serum glucose > 160 mg/dl or hemoglobin A1c > 8% at screening), type 1 or 2
             diabetes mellitus.

          5. Active or untreated brain metastasis

          6. Pleural or pericardial effusion of any grade

          7. Bone only metastases

          8. Patients for whom endocrine therapy is not appropriate (i.e. life threatening
             metastatic disease).

          9. Patients requiring therapeutic anticoagulation (Warfarin 1 mg for port maintenance is
             allowed).

         10. For the Phase II: History of prior malignancies within the past 5 years with the
             exception of curatively treated basal or squamous cell carcinomas of the skin or
             carcinoma in situ of the cervix

         11. Concurrent severe or uncontrolled medical disease (i.e., systemic infection, diabetes,
             hypertension, coronary artery disease, congestive heart failure, ongoing or recent
             gastrointestinal bleed, hepatic or cardiac compromise, hypocalcemia, or known platelet
             function abnormality).

         12. Concomitant medication known to prolong QT interval, unless discontinued >/= 7 days of
             starting dasatinib therapy.

         13. Newly diagnosed (within 3 months before enrollment) or poorly controlled (defined as a
             fasting serum glucose > 160 mg/dl or hemoglobin A1c > 8% at screening), type 1 or 2
             diabetes mellitus.

         14. Active or untreated brain metastasis

         15. Pleural or pericardial effusion of any grade

         16. Bone only metastases

         17. Patients for whom endocrine therapy is not appropriate (i.e. life threatening
             metastatic disease).

         18. Patients requiring therapeutic anticoagulation (Warfarin 1 mg for port maintenance is
             allowed).