A Multicenter Study Evaluating Efficacy and Safety of 177Lu-DOTA-TATE Based on Kidney-Dosimetry in Patients With Disseminated Neuroendocrine Tumors

Inclusion Criteria: Step 1: * ECOG 0-2 * Histologically verified neuroendocrine tumors with a Ki67 of at least 20 % or at least 20 mitoses/high power fields. If the tissue on which this determination is based is several years old, the investigator should consider the option of acquiring a new determination, especially if the behaviour of the tumor has changed since diagnosis * Metastatic disease where complete resection is not considered possible or feasible * Measurable disease * Radiological disease progression during the last 14 months * The largest metastases should have an uptake of 111In-octreotide that is greater than the uptake in the liver by planar scintigraphy. Metastases that are small, or located centrally, can be evaluated by SPECT to enable a correct estimation of the relative uptake. The majority of the tumor burden must demonstrate an increased uptake for lutetium-treatment to be considered * Stable dose of somatostatin analogue for the past 3 months * Estimated survival more than 6 months * ANC more than 1.5 x 10 9/L * Bilirubin less than 1.5 x upper limit of normal * GFR more than 50 ml/min. * Signed written informed concent Step 2: * Continues to fulfill all of the inclusion criteria, and none of the exclusion criteria, from step 1 * A maintained GFR (less than 40 % decrease compared to baseline AND GFR more than 50 ml/min) * The treatment in step 1 have been administered with a maximal interval of 12 weeks * Age under 70 years Exclusion Criteria: Step 1: * Performance Status ECOG 3-4 * Proliferation index (Ki67) more than 20 % or more than 20 mitoses/hpf * Loco-regional treatment during the last 3 months involving all of the measurable lesions * Chemotherapy during the last 3 months, or longer if persisting toxicity exists. Earlier treatment with mTORi or TKI is permitted * Other concommitant nephrotoxic treatment * Modifications of the somatostatine dose in the last 3 months * Serious heart disease * Previous radiotherapy including more than 25 % of active bone marrow volume * Pregnancy and lactation * Extensive liver metastases (more than 50 % of liver volume) * Symptomatic CNS metastases requiring corticosteroid treatment * Ongoing treatment with interferon. This treatment should be suspended a minimum of 4 weeks before treatment with 177Lu-DOTA-TATE, or longer if there is persisting signs of toxicity * Patients who have another metastatic tumor diagnosis Step 2: * Progressive disease since start of study treatment * Organ toxicity grade 3-4 during step 1 * Serious hematological toxicity during previous treatment cycles (ANC less than 0.5 x 10 9 or platelets less than 50.0 x 10 9) * Longstanding diabetes (more than 8 years). Patients with a well-controlled diabetes with a history of less than 8 years and a blood pressure less than 130/80 and no albuminuria (albumin/creatinine index)can be included * Hypertension, i.e. more than 160/90 (for diabetics more than 130/80). Antihypertensive pharmacological treatment is permitted as long as there is no manifest albuminuria * Previous liver embolisation * Previous chemotherapy