A Multicenter Phase II-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