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) atenrollment time, histologically proven, midgut carcinoid tumour (to be centrallyconfirmed).
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 intervalsfor 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 whilereceiving an uninterrupted fixed dose of Octreotide LAR (20-30 mg/3-4 weeks). Diseaseprogression must be centrally confirmed. In order to make the assessment, two CT (orMRI) scans are required. The oldest scan must not be older than 3 years from the dateof randomization. The most recent scan must not be older than 4 weeks from the date ofrandomization. Both scans must be obtained while the patient is receiving the samefixed dose of Octreotide LAR (20-30 mg/3-4 weeks) with the following exceptions; 1) itis acceptable if the oldest scan is obtained within 12 weeks of the patient receivinga fixed dose regimen of Octreotide LAR (20-30 mg/3-4 weeks); AND 2) it is acceptablefor either scan to be obtained before or during the time a patient receiving a fixeddose of Octreotide LAR has switched to an equivalent dose of short acting Octreotidefor up to 6 weeks in order to obtain an OctreoScan®, provided the patient returns tothe Octreotide LAR fixed dose after the OctreoScan® has been obtained.
6. Confirmed presence of somatostatin receptors on all target lesions (fortarget/non-target/measurable lesions definition see §Appendix 2, Section 1 and 2,RECIST Criteria, Version 1.1) documented by CT/MRI scans, based on positiveOctreoScan® imaging within 24 weeks prior to randomization in the study (to becentrally confirmed). The OctreoScan® should be one that was performed while thepatient 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 repeatOctreoScan® performed after 3 months of Octreotide LAR treatments before entering theclinical study to prove that the index lesions or new lesions still meet the criteriafor inclusion. It is acceptable to have patients temporarily switched to Octreotides.c. (up to six weeks) in order to obtain an OctreoScan®, provided they return to thesame fixed dose of Octreotide LAR prior to the scan.
7. The tumour uptake observed in each target lesion (for target/non-target/measurablelesions 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 becentrally 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 affiliatedwith a social security regime or be a beneficiary of the same in order to be includedin the study.

Exclusion Criteria:

1. Either serum creatinine >150 µmol/L (>1.7 mg/dL), or creatinine clearance <50 mL/mincalculated by the Cockroft Gault method, eventually confirmed by measured creatinineclearance (or measured glomerular filtration rate (GFR) using plasma clearancemethods, not gamma camera-based) <50 mL/min (the measured creatinine clearance / GFRis 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 lastmenstruation and not surgically sterile) and male patients, who are not surgicallysterile or with female partners of childbearing potential: absence of effective,non-hormonal means of contraception (intrauterine contraceptive device, barrier methodof 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 torandomization in the study.
8. Peptide receptor radionuclide therapy (PRRT) at any time prior to randomization in thestudy.
9. Any surgery, radioembolization, chemoembolization, chemotherapy and radiofrequencyablation within 12 weeks prior to randomization in the study.
10. Interferons, Everolimus (mTOR-inhibitors) or other systemic therapies within 4 weeksprior to randomization in the study.
11. Known brain metastases, unless these metastases have been treated and stabilized forat least 24 weeks, prior to enrollment in the study. Patients with a history of brainmetastases must have a head CT with contrast to document stable disease prior torandomization 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 beinterrupted 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 byOctreoScan® imaging during continued Octreotide LAR treatment is at least as high asnormal 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 thestudy.
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 insitu of the uterine cervix, unless definitively treated and proven no evidence ofrecurrence for 5 years.
19. Patients who have not provided a signed informed consent form to participate in thestudy, obtained prior to the start of any protocol related activities.
20. Patient with known incompatibility to CT Scans with I.V. contrast due to allergicreaction or renal insufficiency. If such a patient can be imaged with MRI, then thepatient would not be excluded.
21. Patients who have participated in any therapeutic clinical study/received anyinvestigational agent within the last 30 days are excluded from participation in thistrial.