| Exclusion Criteria: | 1) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to three months after the study.
2) WOCBP using a prohibited contraceptive method .
3) Women who are pregnant or breastfeeding.
4) Women with a positive pregnancy test on enrollment or prior to study drug administration.
5) In Part A: Subjects with known brain metastasis. In Part B, subjests who have not documented stable brain metastasis for at least 4 weeks and who are still requiring steriods (Subjects with stable brain metastasis for at leas 4 weeks and are no longer on steroids are eligible for Part B).
6) Subjects with signs or symptoms suggestive of brain metastasis are not eligible unless brain metastases are ruled out by CT or MRI.
7) A serious uncontrolled medical disorder or active infection, which would impair the ability of the subject to receive protocol therapy.
8) History of thromboembolic disease or bleeding diatheses within the last six (6) months. This includes those subjects with tumors that were known to have spontaneously bled in the past. Renal tumor subjects with macroscopic hematuria will be excluded and those renal tumor subjects with microscopic hematuria will be allowed to participate.
9) Current or recent (within 3 months) gastrointestinal disease that could impact the absorption of study drug (e.g. unmanageable diarrhea or malabsorption at the time of screening).
10) Any major surgery within 4 weeks of enrollment
11) Any gastrointestinal surgery that could impact the absorption of study drug.
12) Inability to swallow
13) Uncontrolled or significant cardiovascular disease including: myocardial infarction within 12 months- uncontrolled angina within 6 months, congestive heart failure within 6 months, LVEF </=45% at baseline, or <55% if prior exposure to anthracyclines, diagnosed or suspected congenital long QT syndrome, any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsade de Pointes). Controlled atrial fibrillation is not an exclusion criterion.
14) Continued from exclusion #13: ECG abnormalities as confirmed by repeat assessment, including: prolonged QTc (Bazette's or Fredercia's correction) interval on screening electrocardiogram (>/= 450 msec), QRS > 120 ms, PR > 220 msec, heart rate < 50 beats per minute screening electrocardiogram, any history of second or third degree heart block, Uncontrolled hypertension ( Systolic BP >/= 140 mmHg and diastolic BP >/=90 mmHg), BP must be below 140/90 mmHg at screening.
15) Subjects with concomitant second malignancies (except non-melanomatous skin cancers, early stage prostate or cervical cancers) are excluded unless a complete remission was achieved at least 5 years prior to study entry and no additional therapy is required or anticipated to be required during the study period.
16) Inadequate bone marrow function defined as: absolute neutrophil count < 1,500 cells/mm3, platelet count < 100,000 cells/mm3, hemoglobin < 9.0 g/dl
17) Inadequate hepatic function defined as: total bilirubin > 1.5 times the institutional upper limit of normal (IULN) unless identified as a result of a confirmed genetic disorder of bilirubin metabolism (e.g., Gilbert's syndrome or familial benign unconjugated hyperbilirubinaemia), alanine transaminase (ALT) and aspartate transaminase (AST)> 2.5 times the IULN
18) Inadequate renal function defined as: serum creatinine >1.5 times the IULN
19) PT- INR/PTT >1.5 times the IULN is an exclusion criteria; however, if on prophylactic anti-coagulant, subjects with stable PT-INR/PTT within the institutional target range for the indication (e.g. atrial fibrillation) are permitted following approval from the medical monitor (NOTE: history of thrombo-embolic disease is an exclusion criterion). Drug interactions with warfarin and heparin are not anticipated but close monitoring of anticoagulation status may be warranted.
20) Serum sodium, potassium, calcium and magnesium levels < Grade 1 will be allowed for enrollment. If electrolyte findings on Day -1 are considered not clinically significant, then the Investigator may use his or her discretion to continue with Day 1 treatment.
21) Proteinuria if >/= 1+ then quantify with 24 hr urine collection; eligible if < 1 g/24 hrs
22) History of allergy to BMS-690514 or chemically related compounds
23) Exposure to approved targeted therapies (e.g. erlotinib, gefitinib, etc.) within the last 4 weeks. Part A: Prior use of an EGFR/Her2 or VEGF inhibitor is permitted in subjects entering Part A only. (Subjects may have used an agent of either class, but not both). Part B: Subjects in Part B/Cohort I should be erlotinib naive. Subjects enrolled in Part B/Cohort II should not have used a prior VEGFR inhibitor.
24) Exposure to any investigational drug (including TKIs) within 4 weeks of enrollment.
25) Drugs that are generally accepted to have a risk of causing Torsade de Pointes are prohibited unless prior approval from the medical monitor is obtained. Subjects who have discontinued any of these medications must have a wash-out period of at least 5 days or at least 5 half-lives of the drug whichever is longer) prior to the first dose of BMS-690514.
26) Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study. |