Safety Study of X-82 in Patients With Advanced Solid Tumors

Exclusion Criteria

• •Patients currently receiving cancer therapy (i.e., chemotherapy, radiation therapy, immunotherapy, biologic therapy, hormonal therapy \[with the exception of LHRH agonists for prostate cancer\], surgery and/or tumor embolization).
• •Use of an investigational drug within 21 days or 5 half-lives (whichever is shorter) prior to the first dose of X-82. A minimum of 10 days between termination of the investigational drug and administration of X-82 is required. In addition, any drug-related toxicity should have recovered to grade 1 or less.
• •Any major surgery, radiotherapy, or immunotherapy within the last 21 days (limited palliative radiation is allowed ≥2 weeks). Chemotherapy regimens with delayed toxicity within the last 4 weeks (or within the last 6 weeks for prior nitrosourea or mitomycin C). Chemotherapy regimens given continuously or on a weekly basis with limited potential for delayed toxicity within the last 2 weeks.
• •Patients with a known allergy or delayed hypersensitivity reaction to drugs chemically related to X-82 (sunitinib, sorafenib or pazopanib) or to the active ingredient of X-82.
• •Concomitant use of drugs with a risk of causing prolonged QTc and/or Torsades de Pointes.
• •Concomitant use of herbal medications (i.e. St. John's wort, Kava, ephedra (ma huang), ginko biloba) at least 7 days prior to the first dose of study drug and throughout participation in the trial.
• •Patients with known CNS metastases, unless metastases are treated and stable and the patients do not require systemic steroids
• •Treatment with therapeutic doses of coumarin-type anticoagulants (maximum daily dose of 1mg allowed for port line patency permitted). Low molecular weight heparin (LMWH) will be allowed.
• •Females who are pregnant or breastfeeding.
• •Presence of active gastrointestinal (GI) disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of X-82.
• •Decreased left ventricular function at study entry defined as LVEF \<50% by either Echocardiogram or MUGA scan.
• •Patients who have previously experienced myocardial infarction, severe/unstable angina, coronary/peripheral arterial bypass, symptomatic congestive heart failure (New York Heart Association \[NYHA\] Class 3 or 4), arterial thrombosis, cerebrovascular accident, or transient ischemia, in the 60 days prior to Day 1 of Cycle 1.
• •Patients with inadequately controlled hypertension (defined as BP \> 150/100) with or without current antihypertensive medications. Patients with a history of additional risk factors for Torsades de Pointes (e.g. familial long QT syndrome, heart failure, left ventricular hypertrophy, slow heart rate (\<45 bpm).
• •Patient with a QTcF interval ≥450 msecs or other significant ECG abnormalities as determined the investigator.
• •A serious active infection at the time of treatment, or another serious underlying medical condition that would impair the ability of the patient to receive protocol treatment.
• •Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
• •Concurrent condition that in the investigator's opinion would jeopardize compliance with the protocol
• •Inability or unwillingness to comply with study and/or follow-up procedures outlined in the protocol
• •Patients with a history of intolerance to, or significant toxicity with, VEGFR tyrosine kinase inhibitor(s) (TKI).
• •Patients entering the expansion after the determination of MTD are limited to previous treatment with one anti-VEGFR TKI