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

Study Overview
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Brief Summary
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The purpose of this study is to examine the safety and evaluate the response of VB-111 on DTC.

Conditions
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Differential Thyroid Cancer

Intervention / Treatment
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* Drug: VB-111


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VB-111<br>antiangiogenic and vascular disruptive agent | Drug: VB-111<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival |  | 6 months | 
| Objective response |  | 6 months |