CRIZENT: Crizotinib and Sunitinib in Metastatic Breast Cancer

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.