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. Presence of somatostatin receptor positive tumour(s) on radionuclide imaging, with uptake greater than liver background as assessed by planar Octreoscan® images or Ga-68 labelled somatostatin analogue (68Ga-DOTATATE or 68Ga-HA-DOTATATE) PET imaging, with 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 (smallest dimension) (the target lesion) within 26 weeks of enrolment.
3. Histologically confirmed diagnosis of neuroendocrine tumor.
4. Progressive disease documented by anatomic imaging and/or presence of new lesions on somatostatin receptor imaging assessed by comparable studies. In the opinion of the investigator, patients with no progression on imaging may still be considered eligible in presence of carcinoid symptoms refractory to treatment with somatostatin receptor analogues.
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 GFR of ≥ 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), aspartate transaminase (AST) and alkaline phosphatase) ≤ 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 measured within 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 estimated glomerular filtration rate (GFR) of ≥ 50 mL/min measured within 2 weeks of enrolment.
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), aspartate transaminase (AST) and alkaline phosphatase) ≤ 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 measured within 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 relief permitted as long as target lesion unaffected.
3. Surgery within 12 weeks of enrolment. Surgery for removal of superficial skin lesions, laser eye surgery, or cataract surgery is permitted.
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 of enrolment; chemotherapy and interferon within 8 weeks of enrolment.
7. Change in long acting somatostatin analogues, dosage, or dosage frequency within 12 weeks of enrolment.
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 of normal (or HbA1c > 10%, if results available) within 12 weeks of enrolment.
11. Another significant medical, psychiatric or surgical condition uncontrolled by treatment, which may interfere with completion or conduct of the study (such as urinary 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 more appropriate than the investigational therapy, based on patient and disease characteristics.

Group B (Maintenance Therapy) Exclusion Criteria:

1. Another significant medical, psychiatric or surgical condition uncontrolled by treatment, which may interfere with completion or conduct of the study (such as urinary incontinence or co-existing malignancies).
2. Pregnancy.
3. Breast feeding.