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

Lund University Hospital

Status and phase

Completed

Phase 2

Conditions

Neuroendocrine Tumors

Liver Metastases

Treatments

Drug: 177Lu-DOTA-TATE

Study type

Interventional

Funder types

Other

Identifiers

NCT01456078

EudraCT number: 2011-000240-16

Details and patient eligibility

About

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.

Enrollment

60 patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

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