| Inclusion Criteria: | 1) Adult male or female patients (>/= 18 years of age).
2) Advanced (unresectable or metastatic) biopsy-proven pancreatic NET documented as follows: 1- Radiologic, operative, or pathology reports should document a pancreatic location of tumor at some point in the patient's history; 2- Patients must have confirmed low-grade or intermediate-grade neuroendocrine carcinoma. Pathology report should state one of the following: carcinoid, islet cell carcinoma, pancreatic endocrine tumor, low-grade or well-differentiated neuroendocrine carcinoma, atypical carcinoid, intermediate-grade or moderately differentiated neuroendocrine carcinoma.
3) Documented objective progression of disease by RECIST criteria while receiving cytotoxic chemotherapy or documented progression at any time after receiving an adequate course of cytotoxic chemotherapy (i.e., at least 3 consecutive cycles or months of treatment with the same cytotoxic drug or regimen). Previous therapy with alpha interferon or tyrosine kinase inhibitors are allowed but would not be considered to be prior chemotherapy.
4) Objective progression of disease must be documented by RECIST criteria. Any of the following would be sufficient according to RECIST: a 20% increase in the sum of unidimensionally measured target lesions; a new lesion; unequivocal increase in non-measurable disease.
5) At screening, a triphasic CT or MRI scan must demonstrate measurable disease by RECIST criteria, i.e., the presence of at least one measurable lesion. Measurable disease lesions must be accurately measured in at least one dimension with longest diameter >/= 20 mm using conventional techniques or >/= 10 mm with spiral CT scan (with minimum lesion size no less than double the slice thickness).
6) Adequate bone marrow function as shown by: ANC >/= 1.5 x 10^9/L, Platelets >/= 100 x 10^9/L, Hb >9 g/dL.
7) Adequate liver function as shown by:serum bilirubin </= 1.5 x ULN; INR < 1.3 (or < 3 on anticoagulants); ALT and AST </= 2.5x ULN ( </= 5x ULN in patients with liver metastases).
8) Adequate renal function: serum creatinine </= 1.5 x ULN.
9) Fasting serum cholesterol </=300 mg/dL OR </= 7.75 mmol/L AND fasting triglycerides </= 2.5 x ULN. NOTE: In cases where one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication.
10) Women of childbearing potential must have a negative serum pregnancy test within 14 days of enrollment and/or a urine pregnancy test 48 hours prior to administration of the first study treatment.
11) Appropriate contraception is defined as surgical sterilization (e.g., bilateral tubal ligation, hysterectomy, vasectomy), hormonal contraception (implantable, patch, oral), and doublebarrier methods (any double combination of: IUD, male or female condom with spermicidal gel, diaphragm, sponge, cervical cap).
12) WHO Performance Status 0-2.
13) Signed informed consent to participate in the study must be obtained from patients after they have been fully informed of the nature and potential risks by the investigator (or his/her designee) with the aid of written information.
14) Inclusion criteria for Stratum 2 only: Meet all inclusion criteria defined above for both strata
15) Inclusion criteria for Stratum 2 only: Receiving treatment (at least 3 consecutive months) with Sandostatin LAR® Depot.
16) Inclusion criteria for Stratum 2 only: In addition to documentation of progressive disease on or after chemotherapy, patients in stratum 2 must have documented objective progression of disease while receiving Sandostatin LAR® Depot. The initial and follow-up scans documenting progression must have been obtained during continual monthly therapy with Sandostatin LAR® Depot, with at least 2 months separating the initial and follow-up scans. Progression must be documented by RECIST criteria as described above. |