Pazopanib as Single Agent in Advanced NETs

Inclusion Criteria

• Subjects must provide signed informed consent form prior to performance of study-specific procedures or assessments, and must be willing to comply with treatment and follow-up.

Procedures conducted as part of the subject's clinical routine (e.g., blood count, imaging study) and obtained prior to signing the consent form might be used for screening or baseline purposes provided these procedures have been conducted as specified in the protocol.

• Age ≥ 18 years.
• Diagnosis of pancreatic islet cell tumors, well differentiated gastrointestinal NETs, pulmonary carcinoids and well differentiated thymic carcinoids. Locally-advanced or metastatic disease documented as progressive by CT scan, MRI, or Octreoscan at baseline and within 12 months prior to baseline. The previous scans will be used to classify the patient as having progressive disease at baseline according to RECIST criteria. Octreoscan results may be used to document progressive disease at baseline, but not for RECIST determination during the study.
• ECOG performance status 0-1.
• Disease not amenable to surgery, radiation or combined modality therapy with curative intent.
• Presence of at least one dimensionally measurable target lesion for further evaluation according to RECIST 1.0 criteria (contrast enhancing lesion with the largest diameter > 1cm, based on CT or MRI scan done within 4 weeks before the start of treatment).
• Patients could have received treatment with somatostatin analogs, chemotherapy, anti-VEGF, and anti-mTOR agents previously to the entrance into this study if the final toxicity was grade ≤ 1.
• From patients who sign an informed consent form to donate biological samples: Tumor tissue must be provided for all available subjects at baseline and serum samples will be collected at baseline and at week 12 of treatment for biomarker analysis as defined at the biomarker section of this protocol.
• Adequate organ system function as follows:

9.1.Hematologic system:

• Absolute neutrophil count (ANC) ≥ 1.5 X 10^9/L
• Hemoglobin (1) ≥ 9 g/dL (5.6 mmol/L)
• Platelets ≥ 100 X 10^9/L
• Prothrombin time (PT) or international normalized ratio (INR) ≤ 1.2 X upper limit of normal (ULN)
• Partial thromboplastin time (PTT) ≤ 1.2 X ULN

9.2.Hepatic system (2):

• Total bilirubin ≤ 1.5 X ULN
• AST and ALT ≤ 2.5 X ULN

9.3.Renal system:

• Serum creatinine ≤ 1.5 mg/dL (133 µmol/L),

Or, if greater than 1.5 mg/dL:

• Calculated creatinine clearance ≥ 50 mL/min

(Note 1):"Subjects should not have had a transfusion within 7 days of screening assessment." (Note 2): "Concomitant elevations in bilirubin and AST/ALT above 1.0 x ULN are not permitted"

• A female is eligible to enter and participate in this study if she is of:

10.1.Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who has had:

• A hysterectomy
• A bilateral oophorectomy (ovariectomy)
• A bilateral tubal ligation
• Is post-menopausal

10.2.Childbearing potential, including any female who has had a negative serum pregnancy test within 2 weeks prior to the first dose of study treatment, preferably as close to the first dose as possible, and agrees to use adequate contraception. GETNE acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of the physician, are as follow:

• An intrauterine device with a documented failure rate of less than 1% per year.
• Vasectomized partner who is sterile prior to the female subject's entry and is the sole sexual partner for that female.
• Complete abstinence from sexual intercourse for 14 days before exposure to investigational product, through the dosing period, and for at least 21 days after the last dose of investigational product.
• Double-barrier contraception (condom with spermicidal jelly, foam suppository, or film; diaphragm with spermicide; or male condom and diaphragm with spermicide).
• Oral contraceptives
• Female su