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

Study Overview
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Brief Summary
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By improved kidney dosimetry including biological effective dose and taking into account potential risk factors (especially for kidney toxicity), it might be possible to give an optimal and personalized treatment with 177Lu-DOTA-TATE to the patient with metastatic neuroendocrine tumor.

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

Conditions
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Neuroendocrine Tumors, Liver Metastases

Intervention / Treatment
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* Drug: 177Lu-DOTA-TATE


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 177Lu-DOTA-TATE<br> | Drug: 177Lu-DOTA-TATE<br>* 177Lu-DOTA-TATE given as intravenous infusion given during 3-5 treatments. Evaluation is performed after every single cycle. Further more, evaluation is made after last cycle, and delivered cumulative dose to kidneys should be 27 Gy. Patients with stable disease or partial response, and without pronounced toxicity will continue treatment to a step 2, where additional 3-5 treatment cycles are given, with a cumulative dose to kidneys to 40 Gy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective tumor response after a cumulative kidney biologically effective dose (BED) of 27 +/- 2 Gy |  | 3 months after completed step 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective tumor response after receiving a cumulative BED to the kidneys of 40 +/- 2 Gy as per RECIST v 1.1 |  | 3 months after completing step 2 treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neuroendocrine tumor, Liver metastases, 177Lu-DOTA-TATE, Safety, Kidney dosimetry, Dose escalation, Neuroendocrine tumors, with liver metastases.