A Phase I Study of SOR-C13 in Patients With Advanced Solid Tumors

Exclusion Criteria

• •1. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring intravenous antibiotics, symptomatic congestive heart failure (NYHA Class III or IV), or history of myocardial infarction, unstable angina, stroke or transient ischemic attack within 6 months prior to study enrollment.
• •2. History of clinically significant allergic reactions to the study drugs or their analogs, or any component of the products.
• •3. Any treatment specific for systemic tumor control within 3 weeks prior to the initiation of the study drugs; or within 2 weeks if cytotoxic agents were given weekly (within 6 weeks for nitrosoureas or mitomycin C), or within 5 half-lives for targeted agents with half-lives and pharmacodynamic effects lasting less than 4 days, or failure to recover from toxic effects of any therapy prior to the study drug treatment.
• •4. Patients who have not recovered from major surgical procedure, or significant traumatic injury (i.e., still need additional medical care for these issues).
• •5. History of any of the following cardiovascular events or conditions within the past 6 months prior to enrolment: myocardial infarction, unstable angina, cerebrovascular accident or transient ischemic attack, New York Heart Association Class ≥ II chronic heart failure, significant arrhythmia\*; QTcF interval \>430 msec or use of drugs that prolong the QT interval at screening; family history of long QT syndrome.
• •\*Significant arrhythmias are defined as symptoms of syncope or severe palpitations (palpitations requiring referral to cardiac monitoring), or ECG findings of supraventricular tachycardia (including atrial fibrillation or atrial flutter) or ventricular tachycardia (including ventricular fibrillation) or ventricular ectopy (ventricular premature depolarization)
• •6. Clinically significant and uncontrolled major medical condition(s) that places the subject at an unacceptably high risk for toxicities. These include, but are not limited to: active infections, symptomatic pulmonary disease, inadequate pulmonary function, seizure disorder, or psychiatric illness.
• •7. Current use of more than one antihypertensive medication.
• •8. For patients receiving antihypertensive medication: systolic blood pressure \<120 mm Hg and/or diastolic blood pressure \<70 mm Hg at screening.
• •9. Major surgical procedure within 4 weeks prior to enrolment.
• •10. Lactating or pregnant female.
• •11. Females of childbearing potential and males not using adequate birth control.
• •12. Current treatment or treatment within 4 weeks of screening with bisphosphonates.
• •13. Hypocalcemia at screening.
• •14. History of acute pancreatitis within 6 months prior to screening.
• •15. Known hypoparathyroidism, pseudohypoparathyroidism, or vitamin D deficiency, or clinical evidence of other conditions known to associated with hypocalcemia, including hypoalbuminemia, hyperphosphatemia, hypomagnesemia.
• •16. Current treatment or treatment within 4 weeks of screening with drugs known to reduce serum calcium levels, including: bisphosphonates, antiepileptic drugs, cinacalcet, macrolide antibiotics (such as erythromycin, azithromycin), large doses of corticosteroids (\>20 mg/day of prednisone or equivalent), or any IV use of corticosteroids. In addition, long-term use (defined as ongoing use for ≥4 weeks) of corticosteroids within 8 weeks of screening is prohibited.
• •17. Symptomatic and uncontrolled metastasis to the central nervous system or leptomeningeal or lymphangitic carcinomatosis.
• •18. Grade 2 or higher peripheral neuropathy.
• •19. Human immunodeficiency virus requiring HAART treatment due to unknown drug-drug interactions or known active hepatitis B or C.