A Trial to Assess the Safety and Effectiveness of Lutetium-177 Octreotate Therapy in Neuroendocrine Tumours

Group A (Primary Therapy) Inclusion Criteria:

1. Male or female ≥ 14 - 90 years of age.

2. At least 1 tumour site reliably evaluable by CT or magnetic resonance imaging (MRI)of at least 1.0 cm (smallest dimension) or ≥ 1.5 cm lymph node disease (smallestdimension) (the target lesion) within 26 weeks of enrolment, with documentedpresence of somatostatin receptors on radionuclide imaging, with uptake greater thanliver background as assessed by planar Octreoscan® images or Ga-68 labelledsomatostatin analogue (68Ga-DOTATATE or 68Ga-HA-DOTATATE) PET imaging (or otheravailable somatostatin receptor targeting PET agents) obtained within 1 year ofenrolment. Patients with bone-only disease can be enrolled provided there ispresence of somatostatin receptor positive tumour(s) on radionuclide imagingcorresponding to osteolytic or osteoblastic bone lesions on CT or MRI, with uptakegreater than liver background as assessed by planar Ocgtreoscan(R) images orsomatostatin receptor PET imaging regardless of size.

3. Histologically confirmed diagnosis of neuroendocrine tumor.

4. Progressive disease documented by anatomic imaging and/or presence of new lesions onsomatostatin receptor imaging assessed by comparable studies. In the opinion of theinvestigator, patients with no progression on imaging may still be consideredeligible in presence of carcinoid symptoms refractory to treatment with somatostatinreceptor analogues or functional Pheochromocytoma/Paraganglioma symptoms that arenot well controlled with current medical treatment.

5. 18F-FDG PET/CT whole-body imaging within 26 weeks of enrolment.

6. Life expectancy greater than 12 weeks from enrollment.

7. Serum creatinine ≤ 150 µmol/L, and a calculated (Cockcroft-Gault) or estimated GFRof ≥ 50 mL/min measured within 2 weeks of enrollment.

8. Haemoglobin concentration ≥ 90 g/L; white blood cell (WBC) count ≥ 2 x 10^9/L;platelets ≥ 100 x 10^9/L measured within 2 weeks of enrolment.

9. Liver function tests (total bilirubin, alanine transaminase (ALT), aspartatetransaminase (AST)) ≤ 3X the limit of normal measured within 2 weeks of enrolment.Serum albumin ≥ 23 g/L within 2 weeks of enrolment.

10. Eastern Cooperative Oncology Group (ECOG) Performance Scale Score ≤ 2 measuredwithin 2 weeks of enrolment.

11. Provide written informed consent prior to enrolment.

Group B (Maintenance Therapy) Inclusion Criteria:

1. Male or female ≥ 14 - 90 years of age.

2. Have previously received Lu-DOTA-TATE treatment under the SAP.

3. Life expectancy greater than 12 weeks from enrolment.

4. Serum creatinine ≤ 150 μmol/L, and a calculated (Cockcroft-Gault) or estimatedglomerular filtration rate (GFR) of ≥ 50 mL/min measured within 2 weeks ofenrolment.

5. Haemoglobin concentration ≥ 90 g/L; white blood cell (WBC) count ≥ 2 x 10^9/L;platelets ≥ 100 x 10^9/L measured within 2 weeks of enrolment.

6. Liver function tests (total bilirubin, alanine transaminase (ALT), aspartatetransaminase (AST)) ≤ 3X the limit of normal measured within 2 weeks of enrolment.Serum albumin ≥ 23 g/L within 2 weeks of enrolment.

7. Eastern Cooperative Oncology Group (ECOG) Performance Scale Score ≤ 2 measuredwithin 2 weeks of enrolment.

8. Provide written informed consent prior to enrolment.

Group A (Primary Therapy) Exclusion Criteria:

1. Have previously received Lu-DOTA-TATE therapy.

2. Potential for surgery with curative intent. Local surgery for symptomatic reliefpermitted as long as target lesion unaffected.

3. Major surgery within 12 weeks of enrolment. Minor surgeries such as removal ofsuperficial skin lesions, laser eye surgery, cataract surgery, laparoscopicprocedures and other procedures that are minimally invasive are permitted at theInvestigator's discretion.

4. Liver embolization [transcatheter arterial embolization (TAE), TACE, or TARE] within 4 weeks of enrolment.

5. Radioisotope therapy within 12 weeks of enrolment.

6. Systemic therapy: mTOR inhibitors and tyrosine kinase inhibitors within 6 weeks ofenrolment; chemotherapy and interferon within 8 weeks of enrolment.

7. Change in long-acting somatostatin analogues, dosage, or dosage frequency within 12weeks of enrolment unless changes are required to manage uncontrolled symptoms.

8. Localized external beam irradiation with target lesion(s) in the radiation field.Other localized external beam therapy is permitted.

9. Known brain metastases unless these metastases have been treated and stabilized (confirmed by CT) for ≥ 4 months prior to enrolment

10. Uncontrolled diabetes mellitus defined as random glucose ≥ 2X the upper limit ofnormal (or HbA1c > 10%, if results available) within 12 weeks of enrolment.

11. Another significant medical, psychiatric or surgical condition uncontrolled bytreatment, which may interfere with completion or conduct of the study (such asurinary incontinence, co-existing malignancies).

12. Pregnancy.

13. Breast feeding.

14. Prior radiation therapy to more than 25% of the bone marrow.

15. If, in the opinion of the investigator, other treatments are considered moreappropriate than the investigational therapy, based on patient and diseasecharacteristics.

16. Known allergy to somatostatin analogues or any components of the study medication.

Group B (Maintenance Therapy) Exclusion Criteria:

1. Another significant medical, psychiatric or surgical condition uncontrolled bytreatment, which may interfere with completion or conduct of the study (such asurinary incontinence or co-existing malignancies).

2. Pregnancy.

3. Breast feeding.

4. Known allergy to somatostatin analogues or any components of the study medication.