A Multicentre, Stratified, Open, Randomized, Comparator-controlled, Parallel-group Phase III Study Comparing Treatment With 177Lu-DOTA0-Tyr3-Octreotate to Octreotide LAR in Patients With Inoperable, Progressive, Somatostatin Receptor Positive Midgut Carcinoid Tumours

Inclusion Criteria:

- Presence of inoperable (curative intent) at enrolment time, histologically proven,
midgut carcinoid tumour.

- Ki67 index ≤ 20%.

- 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 enrolment in the study.

- Patients ≥18 years of age.

- Patients must have progressive disease based on RECIST Criteria, Version 1.1
evidenced with CT scans/MRI within 3 years from enrolment; previous images must be
centrally evaluated to confirm the disease progression under previous therapy:for the
purpose of determining disease progression the oldest CT/MRI scan must not be older
than 3 years and the most recent scan must not be older than 4 weeks from the
projected randomization date. The CT scan/MRI scan should be one that was performed
while the patient was on a fixed dose of Sandostatin LAR.

- Confirmed presence of somatostatin receptors on all technically evaluable tumour
lesions documented by CT/MRI scans, based on positive OctreoScan® imaging within 24
weeks prior to enrolment in the study.

- The tumour uptake observed using OctreoScan® must be ≥ normal liver uptake observed
on planar imaging.

- Karnofsky Performance Score (KPS) ≥ 60

- Presence of at least 1 measurable site of disease.

Exclusion Criteria:

- Serum creatinine >150 µmol/L or 1.7 mg/dL, or a measured creatinine clearance (or
measured glomerular filtration rate (GFR) using plasma clearance methods, not gamma
camera-based) of <50 mL/min.

- Hb concentration <5.0 mmol/L (<8.0 g/dL); WBC <2x10^9/L (2000/mm3); platelets
<75x10^9/L (75x10^3/mm3).

- Total bilirubin >3 x upper limit of normal (ULN).

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

- Pregnancy

- 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)

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

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

- Targeted surgery, radiotherapy (external beam), chemotherapy, embolization,
interferons, mammalian target of rapamycin (mTOR)-inhibitors or other investigational
therapy within 12 weeks prior to enrolment in the study.

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

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

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

- Any patient who has both OctreoScan® positive and negative tumours.

- 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 observed by OctreoScan® imaging
during continued Octreotide treatment is at least as high as normal liver uptake
observed by planar imaging.

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

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

- Urinary incontinence.

- 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.

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

- Patient with known incompatibility to CT Scans with I.V. contrast due to allergic
reaction or renal insufficiency.