A Study Comparing Treatment With 177Lu-DOTA0-Tyr3-Octreotate to Octreotide LAR in Patients With Inoperable, Progressive, Somatostatin Receptor Positive Midgut Carcinoid Tumours

Inclusion Criteria:

   1. Presence of metastasized or locally advanced, inoperable (curative intent) at
   enrollment time, histologically proven, midgut carcinoid tumour (to be centrally
   confirmed).

   2. Ki67 index ≤ 20% (to be centrally confirmed).

   3. Patients on Octreotide LAR at a fixed dose of 20 mg or 30 mg at 3-4 weeks intervals
   for at least 12 weeks prior to randomization in the study.

   4. Patients ≥18 years of age.

   5. Patients must have progressive disease based on RECIST Criteria, Version 1.1 while
   receiving an uninterrupted fixed dose of Octreotide LAR (20-30 mg/3-4 weeks). Disease
   progression must be centrally confirmed. In order to make the assessment, two CT (or
   MRI) scans are required. The oldest scan must not be older than 3 years from the date
   of randomization. The most recent scan must not be older than 4 weeks from the date of
   randomization. Both scans must be obtained while the patient is receiving the same
   fixed dose of Octreotide LAR (20-30 mg/3-4 weeks) with the following exceptions; 1) it
   is acceptable if the oldest scan is obtained within 12 weeks of the patient receiving
   a fixed dose regimen of Octreotide LAR (20-30 mg/3-4 weeks); AND 2) it is acceptable
   for either scan to be obtained before or during the time a patient receiving a fixed
   dose of Octreotide LAR has switched to an equivalent dose of short acting Octreotide
   for up to 6 weeks in order to obtain an OctreoScan®, provided the patient returns to
   the Octreotide LAR fixed dose after the OctreoScan® has been obtained.

   6. Confirmed presence of somatostatin receptors on all target lesions (for
   target/non-target/measurable lesions definition see §Appendix 2, Section 1 and 2,
   RECIST Criteria, Version 1.1) documented by CT/MRI scans, based on positive
   OctreoScan® imaging within 24 weeks prior to randomization in the study (to be
   centrally confirmed). The OctreoScan® should be one that was performed while the
   patient was on a fixed dose of Octreotide LAR. If a patient has had an OctreoScan®
   performed while Octreotide LAR treatment-naïve, the patient must have a repeat
   OctreoScan® performed after 3 months of Octreotide LAR treatments before entering the
   clinical study to prove that the index lesions or new lesions still meet the criteria
   for inclusion. It is acceptable to have patients temporarily switched to Octreotide
   s.c. (up to six weeks) in order to obtain an OctreoScan®, provided they return to the
   same fixed dose of Octreotide LAR prior to the scan.

   7. The tumour uptake observed in each target lesion (for target/non-target/measurable
   lesions definition see §Appendix 2, Sections 1 and 2, RECIST Criteria, Version 1.1)
   using OctreoScan® must be ≥ normal liver uptake observed on planar imaging (to be
   centrally confirmed) (§Appendices 5 and 6).

   8. Karnofsky Performance Score (KPS)>=60.

   9. Presence of at least 1 measurable site of disease.

10. [Applicable only for France] All patients included in the trial must be affiliated
   with a social security regime or be a beneficiary of the same in order to be included
   in the study.

Exclusion Criteria:

   1. Either serum creatinine >150 µmol/L (>1.7 mg/dL), or creatinine clearance <50 mL/min
   calculated by the Cockroft Gault method, eventually confirmed by measured creatinine
   clearance (or measured glomerular filtration rate (GFR) using plasma clearance
   methods, not gamma camera-based) <50 mL/min (the measured creatinine clearance / GFR
   is required only as confirmatory exam).

   2. Hb concentration <5.0 mmol/L (<8.0 g/dL); WBC <2x109/L (2000/mm3); platelets <75x109/L
   (75x103/mm3).

   3. Total bilirubin >3 x ULN.

   4. Serum albumin <3.0 g/dL unless prothrombin time is within the normal range.

   5. Pregnancy or lactation.

   6. For female patients of childbearing potential (defined as < 2 years after last
   menstruation and not surgically sterile) and male patients, who are not surgically
   sterile or with female partners of childbearing potential: absence of effective,
   non-hormonal means of contraception (intrauterine contraceptive device, barrier method
   of contraception in conjunction with spermicidal gel) as defined in §Appendix 7.

   7. Treatment with >30 mg Octreotide LAR at 3-4 weeks intervals within 12 weeks prior to
   randomization in the study.

   8. Peptide receptor radionuclide therapy (PRRT) at any time prior to randomization in the
   study.

   9. Any surgery, radioembolization, chemoembolization, chemotherapy and radiofrequency
   ablation within 12 weeks prior to randomization in the study.

10. Interferons, Everolimus (mTOR-inhibitors) or other systemic therapies within 4 weeks
   prior to randomization in the study.

11. Known brain metastases, unless these metastases have been treated and stabilized for
   at least 24 weeks, prior to enrollment in the study. Patients with a history of brain
   metastases must have a head CT with contrast to document stable disease prior to
   randomization in the study.

12. Uncontrolled congestive heart failure (NYHA II, III, IV).

13. Uncontrolled diabetes mellitus as defined by a fasting blood glucose >2 ULN.

14. Any patient receiving treatment with short-acting Octreotide, which cannot be
   interrupted for 24 h before and 24 h after the administration of
   177Lu-DOTA0-Tyr3-Octreotate, or any patient receiving treatment with Octreotide LAR,
   which cannot be interrupted for at least 6 weeks before the administration of
   177Lu-DOTA0-Tyr3-Octreotate, unless the tumour uptake on target lesions observed by
   OctreoScan® imaging during continued Octreotide LAR treatment is at least as high as
   normal liver uptake observed by planar imaging.

15. Patients with any other significant medical, psychiatric, or surgical condition,
   currently uncontrolled by treatment, which may interfere with the completion of the
   study.

16. Prior external beam radiation therapy to more than 25% of the bone marrow.

17. Current spontaneous urinary incontinence.

18. Other known co-existing malignancies except non-melanoma skin cancer and carcinoma in
   situ of the uterine cervix, unless definitively treated and proven no evidence of
   recurrence for 5 years.

19. Patients who have not provided a signed informed consent form to participate in the
   study, obtained prior to the start of any protocol related activities.

20. Patient with known incompatibility to CT Scans with I.V. contrast due to allergic
   reaction or renal insufficiency. If such a patient can be imaged with MRI, then the
   patient would not be excluded.

21. Patients who have participated in any therapeutic clinical study/received any
   investigational agent within the last 30 days are excluded from participation in this
   trial.