This study will investigate the safety, symptoms and biomarker response of subjects with biopsy-proven well-differentiated, low-to-intermediate-grade, unresectable, or metastatic pancreatic neuroendocrine tumors (PNETs) or or Gastrointestinal Neuroendocrine tumors (GI-NETs) with elevated biochemical markers who have relapsed during or after receiving prior standard of care therapies, including octreotide, chemotherapy or targeted therapy.

Subjects enrolled in this PNET/GI-NET study (OX4218s) will receive weekly dosing with fosbretabulin for up to 3 cycles or approximately 9 weeks.

Inclusion Criteria:

• Ability to read, understand and provide written consent to participate in the study

• Age ≥ 18 years

• Biopsy-proven well-differentiated, low-to-intermediate-grade PNET or GI-NET with elevated (> ULN) biomarkers (serotonin, 5-hydroxyindoleacetic acid (5-HIAA), chromogranin A (CgA), neurokinin A, and neuron-specific enolase (NSE))

• Life expectancy > 12 weeks

• Must have received or may still be receiving one or more therapies including octreotide or serotonin synthesis inhibitor (SSI) or other somatostatin analogues

• Confirmed progressive disease within 18 months of enrollment on study

• Recovered from prior radiation therapy or surgery

• Eastern Cooperative Oncology Group (ECOG) performance score 0-2

• Absolute neutrophil count (ANC) ≥ 1,500/µL (without growth factors)

• Platelet count ≥ 100,000/µL

• Adequate renal function as evidenced by serum creatinine

  ≤ 2.0 mg/dL (177 µmol/L)

• Adequate hepatic function: serum total bilirubin ≤ 2X greater than the upper limit of normal (ULN) (≤ 3X ULN in subjects with liver metastases), aspartate aminotransferase) AST) / alanine aminotransferase (AST) ≤ 2X the ULN for the local reference lab (≤ 5X the ULN for subjects with liver metastases)

• Disease that can be assessed (evaluable) with imaging (CT, MRI, PET, radionuclide imaging or other imaging modality)

• Women of childbearing potential as well as fertile men and their partners must use an effective method of birth control

Exclusion Criteria:

• Inadequately controlled hypertension defined as BP > 150/100 mm Hg despite medication
• Prior history of hypertensive crisis or hypertensive encephalopathy
• Recent history (within 6 months of start of screening) of unstable angina pectoris pattern, myocardial infarction (including non-Q wave MI), or NYHA (New York Heart Association) Class III and IV Congestive Heart Failure (CHF)
• Subjects who have clinical evidence of carcinoid-induced heart disease
• History of prior cerebrovascular accident (CVA), including transient ischemic attach (TIA)
• Known central nervous system (CNS) disease except for treated brain metastasis
• History of torsade de pointes, ventricular tachycardia or fibrillation, pathologic sinus bradycardia (<60 bpm), heart block (excluding 1st degree block, being PR interval prolongation only), congenital long QT syndrome or new ST segment elevation or depression or new Q wave on ECG
• Corrected QT interval (QTc) > 480 msec
• Ongoing treatment with any drugs known to prolong the QTc interval, including anti-arrhythmic medications (stable regimen of antidepressants of the selective serotonin reuptake inhibitor (SSRI) class is allowed))
• Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
• Significant vascular disease or recent peripheral arterial thrombosis
• Known intolerance of or hypersensitivity to fosbretabulin
• History of solid organ transplant or bone marrow transplant
• Any other intercurrent medical condition, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a subject's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results
• High grade or poorly differentiated NET
• NET tumor other than PNET or GI-NET
• No elevated biomarker (>ULN) that can be followed
• Received regional hepatic infusion therapy within 6 months of enrollment (RFA allowed >6 months prior to enrollment)