Safety and Efficacy of VB-111 in Subjects With Advanced Differentiated Thyroid Cancer

Inclusion criteria

• Histologically or cytologically confirmed advanced DTC (papillary, follicular, Hurthle cell);
• Absence of sensitivity to therapeutic radioiodine;
• Measurable disease, defined as at least one non-bony lesion that can be accurately measured in at least one dimension as confirmed with spiral CT scan
• Life expectancy >3 months; ECOG performance status (PS) 0, 1, or 2; Karnofsky performance status of ≥60%;
• Subjects with a normal/acceptable hematological profile
• Subjects with adequate renal function

Exclusion criteria

• Presence of any of the following:

• Radiotherapy or chemotherapy <4 weeks prior to baseline visit; (Concurrent and/or prior therapy with octreotide will be allowed, provided tumor progression on this therapy has been demonstrated; Concurrent and/or prior therapy with biphosphonates will be allowed)
• Radiotherapy to ≥25% of bone marrow;
• Major surgery <4 weeks prior to baseline visit;
• Any other ongoing investigational agents within 4 weeks before dosing;
• Subjects who suffered from an acute cardiac event within the last 12 months, including myocardial infarction, cardiac arrythmia, admission for unstable angina, cardiac angioplasty, or stenting;
• QTc prolongation (defined as QTc interval ≥500 msecs) or other significant ECG abnormalities (e.g. frequent ventricular ectopy, evidence of ongoing myocardial ischemia);
• Subjects with active vascular disease, either myocardial or peripheral;
• Subjects with proliferative and/or vascular retinopathy;
• Subjects with known active liver disease (alcoholic, drug/toxin induced, genetic, or autoimmune) other than related to tumor metastases;
• Subjects with known CNS metastatic disease (Exception: Subjects with treated CNS metastases stable by radiographic examinations >6 months after definitive therapy administered, are eligible);
• Subjects testing positive to one of the following viruses: HIV, HBV or HCV;
• Any of the following conditions:

• Serious or non-healing wound, ulcer, or bone fracture;
• History of abdominal fistula, gastro-intestinal perforation, active diverticulitis, intra-abdominal abscess or gastro-intestinal tract bleeding within 6 months of dosing;
• Any history of cerebrovascular accident (CVA) within 6 months of dosing;
• Current use of therapeutic warfarin (Note: Low molecular weight heparin and prophylactic low-dose warfarin [INR<1.2 X ULN] are permitted);
• History of bleeding disorder, including subjects with hemophilia, disseminated intravascular coagulation (DIC), or any other abnormality of coagulation potentially predisposing subjects to bleeding;
• Poorly controlled depression or anxiety disorder, or recent (within the previous 6 months) suicidal ideation;
• Subjects with an ongoing requirement for immunosuppressive treatment, including the use of glucocorticoids or cyclosporin, or with a history of chronic use of any such medication within the last 4 weeks before dosing;
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements.