Clinical Trial · NCT01456078

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

Overview

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.

Sponsor

Turku University Hospital

Phase

Phase 2

Contacts

Jan Tennvall, MD, PhD (PRINCIPAL_INVESTIGATOR)

ClinicalTrials.gov

NCT01456078

Drug / Compound

DOTATATE

Isotope(s):
Target(s):
  • SSTR2
Ligand Class: Peptides
Chelator: DOTA

Eligibility

Inclusion

  • ECOG 0-2
  • 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
  • GFR more than 50 ml/min.
  • Metastatic disease where complete resection is not considered possible or feasible
  • Measurable disease
  • Signed written informed concentStep 2:
  • Step 1:
  • 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)
  • Estimated survival more than 6 months
  • The treatment in step 1 have been administered with a maximal interval of 12 weeks
  • ANC more than 1.5 x 10 9/L
  • Stable dose of somatostatin analogue for the past 3 months
  • Radiological disease progression during the last 14 months
  • Bilirubin less than 1.5 x upper limit of normal

Exclusion

  • Previous chemotherapy
  • Progressive disease since start of study treatment
  • Patients who have another metastatic tumor diagnosisStep 2:
  • Previous liver embolisation
  • 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
  • Pregnancy and lactation
  • Performance Status ECOG 3-4
  • Serious hematological toxicity during previous treatment cycles (ANC less than 0.5 x 10 9 or platelets less than 50.0 x 10 9)
  • Loco-regional treatment during the last 3 months involving all of the measurable lesions
  • 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
  • Modifications of the somatostatine dose in the last 3 months
  • Organ toxicity grade 3-4 during step 1
  • Serious heart disease
  • Chemotherapy during the last 3 months, or longer if persisting toxicity exists. Earlier treatment with mTORi or TKI is permitted
  • 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
  • Step 1:
  • Extensive liver metastases (more than 50 % of liver volume)
  • Symptomatic CNS metastases requiring corticosteroid treatment
  • Previous radiotherapy including more than 25 % of active bone marrow volume
  • Proliferation index (Ki67) more than 20 % or more than 20 mitoses/hpf
  • Other concommitant nephrotoxic treatment