A Study to Assess the Safety and the Efficacy of the Combination of TH-302 and Sunitinib in Neuroendocrine Pancreatic Tumours

Inclusion Criteria: * Male or female, 18 years of age or older. * Eastern Cooperative Oncology Group (ECOG) performance status 0-1. * Histologically proven diagnosis of pancreatic neuroendocrine tumors (pNET) with Ki67 assessment of ≤ 20% (well and moderately differentiated) * Evidence of unresectable disease or metastatic disease. Locally advanced disease must not be amendable to resection or radiation therapy with curative intent. * Patients may be treated with somatostatin analogues prior or during the trial. Concomitant or prior interferon treatment is not permitted. * Documented progression disease by CT scan, magnetic resonance (MR) or Octreoscan in 12 months prior basal visit. * Measurable disease as per RECIST. Measurable lesions that have been previously radiated will not be considered target lesions unless increase in size has been observed following completion of radiation therapy. * Patient has to be able to swallow the medication. * Life expectancy greater than 12 weeks. * The definitions of minimum adequacy for organ function required prior to study entry are as follows: * Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤ 2.5 x upper limit of normal (ULN), or AST and ALT ≤ 5 x ULN if liver function abnormalities are due to underlying malignancy * Total serum bilirubin ≤ 1.5 x ULN * Serum albumin ≥ 3.0 g/dL * Absolute neutrophil count (ANC) ≥ 1500/µL * Platelets ≥ 100,000/µL * Hemoglobin ≥ 5,6 mmol/L (9.0 g/dL) * Creatinin clearance \> 40 mL/min (Cockcroft and Gault formula) * Adequate cardiac function: 12-lead ECG without pathologic findings (clinically significant alterations are allowed) and Echocardiogram / Normal multiple gated acquisition scan (MUGA) (LVEF\> 50%) * Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all the pertinent aspects of the trial prior to enrollment. * Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures. Exclusion Criteria: * Previous treatments with chemotherapy, monoclonal antibodies anti-vascular endothelial growth factor (VEGF), tyrosine kinase inhibitors, mammalian target of rapamycin (mTOR) inhibitors, or interferon are not permitted for the advanced disease. * Prior treatment on another hypoxia-activated prodrug under clinical trial. * Major surgery, radiation therapy, or systemic therapy within 3 weeks of study randomization except palliative radiotherapy to non-target metastatic lesions. * Prior high-dose chemotherapy requiring hematopoietic stem cell rescue. * Immunosuppressive drugs such as cyclosporine, tacrolimus, azathioprine, or long-term oral glucocorticoids taken concurrently or within last 3 months prior to randomization * Treatment with known inhibitors or inductors of cytochrome P450 3A4 (CYP3A4) or that prolong the QT interval in the previous 7 days. * Prior radiation therapy to \> 25% of the bone marrow. * Current treatment on another clinical trial. * Uncontrolled brain metastases, spinal cord compression, carcinomatous meningitis, or leptomeningeal disease. Patients should have completed surgery or radiation therapy for existing brain metastases, should not have documented increase in size over the previous 3 months prior to first dose of treatment on study and should be asymptomatic. * Diagnosis of any second malignancy within the last 3 years, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix. * Any of the following within the 12 months prior to starting study treatment: * myocardial infarction, * severe/unstable angina, * coronary/peripheral artery bypass graft, * congestive heart failure class III or IV of the New York Heart Association (NYHA) or patients with clinical history of congestive heart failure class III or IV of the NYHA, unless an echocardiogram or MUGA in the previous 3 months to selection shows a LVEF ? 45 % * significant heart valve disease * cerebrovascular accident including transient ischemic attack * pulmonary embolus. * Ongoing cardiac dysrhythmias of NCI Common Toxicity Criteria for Adverse Effects (CTCAE) grade ≥ 2, atrial fibrillation of any grade, or corrected QT interval (QTc) interval \>450 msec for males or \>470 msec for females. * Hypertension that cannot be controlled by medications (\>150/100 mmHg despite optimal medical therapy) * Chronic obstructive pulmonary disease (COPD) or any other disease concurrent with hypoxemia or oxygen saturation \< 90% after a march of two minutes. * Current treatment with therapeutic doses of Coumadin (low dose Coumadin up to 2 mg PO daily for deep vein thrombosis prophylaxis is allowed). * Known human immunodeficiency virus infection. * Pregnancy or breastfeeding. All female patients with reproductive potential must have a negative pregnancy test (serum or urine) prior to inclusion. * Previous allergic reaction to components structurally similar to TH-302 or sunitinib or any of the excipients of drugs. * Non-healing wound, fistulae, active peptic ulcer or bone fracture. * Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration, or which, in the judgment of the investigator, would make the patient inappropriate for entry into this study.