Clinical trial NCT02074878 (phase 1, status: terminated)
Conditions: breast cancer
ICD codes: C79.81, D24.1, D24.2, D24.9, D49.3, C44.501, D48.60
Drugs: crixotinib 200 mg and sunitinib cohort 1, crixotinib 250 mg and sunitinib cohort 2, crizotinib & sunitinib 37.5 mg cohort 3
SMILES: CNC(=O)C1=C(SC2=CC=C3C(NN=C3\C=C\C3=CC=CC=N3)=C2)C=CC=C1, CNC(=O)C1=C(SC2=CC=C3C(NN=C3\C=C\C3=CC=CC=N3)=C2)C=CC=C1, C[C@@H](OC1=CC(=CN=C1N)C1=CN(N=C1)C1CCNCC1)C1=C(Cl)C=CC(F)=C1Cl
Reason stopped: 
    poor accrual so the study was halted on may 16, 2017.
  
Eligibility criteria:

        Inclusion Criteria:

          1. Subjects must provide written informed consent prior to performance of study-specific
             procedures or assessments, and must be willing to comply with treatment and follow-up.

          2. Age of at least 18 years

          3. Histologically confirmed diagnosis of stage IV, HER2 negative breast cancer.

          4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

          5. Patients must have failed two lines of systemic therapy for breast cancer. Patients
             who are hormone receptor positive must have failed at least one line of hormonal
             therapy AND one line of chemotherapy in the metastatic setting.

          6. Life expectancy of 6 months or more.

          7. Liver function (ALT, AST, alkaline phosphatase, total bilirubin) and kidney function
             tests (BUN, creatinine) less than 2.5 times the upper limit of normal. In patients
             with liver metastasis, liver function tests should be less than 5 times the upper
             limit of normal.

          8. Adequate blood counts (Hemoglobin greater than/equal to 10, WBC greater than/equal to
             3.0, platelets greater than/equal to 100).

          9. The patient has normal thyroid function tests (TSH, free T4) as defined by the testing
             laboratory, a test abnormality that is asymptomatic and does not warrant medical
             intervention, or a pre-existing thyroid disorder that is controlled on medical
             treatment.

         10. Negative pregnancy test (BHCG) within 14 days of study drug initiation for pre- or
             perimenopausal subjects with an intact uterus.

        Exclusion Criteria:

          1. Clinically significant gastrointestinal abnormalities that may increase the risk for
             gastrointestinal bleeding.

          2. Clinically significant gastrointestinal abnormalities that may affect absorption of
             investigational products.

          3. Presence of uncontrolled infection.

          4. Corrected QT interval (QTc) > 480 msecs using Bazett's formula

          5. History of any one or more of the following cardiovascular conditions within the past
             6 months: - Cardiac angioplasty or stenting - Myocardial infarction - Unstable angina
             - Coronary artery bypass graft surgery - Symptomatic peripheral vascular disease -
             Class III or IV congestive heart failure, as defined by the New York Heart Association
             (NYHA)

          6. Poorly controlled hypertension (defined as systolic blood pressure [SBP] of > 150 mmHg
             or diastolic blood pressure [DBP] of > 90 mmHg).

          7. History of cerebrovascular accident including transient ischemic attack (TIA),
             pulmonary embolism, or untreated deep venous thrombosis (DVT) within the past 6
             months. Subjects with recent DVT who have been treated with therapeutic
             anti-coagulating agents for at least 6 weeks are eligible.

          8. Prior major surgery or trauma within 28 days prior to first dose of study drug and/or
             presence of any non-healing wound, fracture, or ulcer (procedures such as catheter
             placement not considered to be major).

          9. Evidence of active bleeding or bleeding diathesis.

         10. Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels

         11. Hemoptysis in excess of 2.5 mL (or one half teaspoon) within 8 weeks prior to first
             dose of study drug.

         12. Any serious and/or unstable pre-existing medical, psychiatric, or other condition that
             could interfere with subject's safety, provision of informed consent, or compliance to
             study procedures.

         13. Patients previously treated with sunitinib or crizotinib.

         14. History of other malignancy within the last 5 years, except for carcinoma in situ of
             the cervix or basal cell carcinoma of the skin.

         15. Concurrent use of: - Potent CYP3A4 inhibitors: ketoconazole, itraconazole,
             clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir,
             amprenavir, indinavir, nelfinavir, delavirdine and voriconazole. - CYP3A4 inducers:
             rifampin, rifabutin, rifapentin, phenobarbital, phenytoin, carbamazepine, St. John's
             Wort, and dexamethasone. Use of dexamethasone for study premedication is allowed. -
             Grapefruit and grapefruit juice. (Note: Alternative therapies should be used when
             available. If use of a potent CYP3A4 inhibitor or inducer is necessary, this must be
             approved by the principal investigator and documented in source documents).

         16. History of receiving any investigational treatment within 28 days of study medication
             initiation.

         17. Current severe, uncontrolled systemic disease (e.g., clinically significant
             cardiovascular, pulmonary, thyroid, or metabolic disease; wound healing disorders;
             ulcers; or bone fractures).

         18. Patients who are pregnant or lactating.