A Study Comparing Treatment With 177Lu-DOTA0-Tyr3-Octreotate to Octreotide LAR in Patients With Inoperable, Progressive, Somatostatin Receptor Positive Midgut Carcinoid Tumours (NETTER-1)

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.