Inclusion Criteria:

1. Confirmed low to intermediate grade neuroendocrine tumors with unresectable liver
metastasis

2. Patients must have evidence of disease progression by RECIST despite optimal
octreotide therapy (octreotide LAR 30 mg every month)

3. Prior treatment permitted include: surgery, prior systemic therapies (less than 2
prior lines of chemotherapy), or radiation therapy.

4. Patients must have measurable disease by RESICT 1.1 criteria.

5. For the patients in the phase Ib study, neuroendocrine tumor must involve both liver
lobes.

6. Minimum of four weeks since any major surgery, completion of radiation, or completion
of all prior systemic anticancer therapy (adequately recovered from the acute
toxicities of any prior therapy).

7. Age greater than 18 years

8. Adequate bone marrow function as shown by: ANC greater than or equal to 1.5 x 109 L,
Platelets greater than or equal to 100 x 109/L, Hb greater than9 g dL

9. Adequate liver function as shown by:

- serum bilirubin less than or equal to 1.5 x ULN

- ALT and AST less than or equal to 2.5x ULN (less than or equal to 5x ULN in
patients with liver metastases)

- INR less than or equal to 1.5. (Anticoagulation is allowed if target INR less
than or equal to 1.5 on a stable dose of warfarin or on a stable dose of LMW
heparin for grater than 2 weeks at time of randomization.)

10. Adequate renal function: serum creatinine less than or equal to 1.5 x ULN

Exclusion Criteria:

1. Contraindications to angiography

2. Patients with extensive tumor replacement of the liver defined as tumor volume
greater than 50 percent of liver

3. Prior treatment with any investigational drug within the preceding 4 weeks

4. Uncontrolled brain or leptomeningeal metastases, including patients who continue to
require glucocorticoids for brain or leptomeningeal metastases

5. Patients who have any severe and/or uncontrolled medical conditions or other
conditions that could affect their participation in the study such as:

- Symptomatic congestive heart failure of New York heart Association Class III or
IV

- unstable angina pectoris, symptomatic congestive heart failure, myocardial
infarction within 6 months of start of study drug, serious uncontrolled cardiac
arrhythmia or any other clinically significant cardiac disease

- severely impaired lung function as defined as spirometry and DLCO that is 50
percent of the normal predicted value and/or 02 saturation that is 88 percent or
less at rest on room air

- uncontrolled diabetes as defined by hemoglobin A1C (HbA1c) greater than 7
percent despite therapy.

- active (acute or chronic) or uncontrolled severe infections

- liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class
C).

6. A detailed assessment of Hepatitis B/C medical history and risk factors must be done
at screening for all patients. HBV DNA and HCV RNA PCR testing are required at
screening for all patients with a positive medical history based on risk factors
and/or confirmation of prior HBV/HCV infection. See section 3.2.5.1 for the detailed
management and monitoring of patients with HBV/HCV infection on trial.

7. Patients with the presence of active or suspected acute or chronic uncontrolled
infection or with a history of immunocompromise, including a positive HIV test result
(ELISA and Western blot).

8. Patients with an active, bleeding diathesis

9. Patients who have received prior treatment with an mTOR inhibitor (e.g., sirolimus,
temsirolimus, everolimus).

10. Known hypersensitivity to somatostatin analogues or any component of the pasireotide
or octreotide LAR formulations