Gastroenteropancreatic neuroendocrine tumours, GEP-NET's. MedDRA version: 14.1 Level: LLT Classification code 10062476 Term: Neuroendocrine tumor System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 14.1 Level: PT Classification code 10071542 Term: Neuroendocrine carcinoma metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Pharmaceutical Form:
INN or Proposed INN: 177Lu-DOTATATE
Concentration unit: Bq/ml becquerel(s)/millilitre
Concentration type: range
Concentration number: 500000-1100000
Sponsors
Department of Nuclear Medicine, Odense University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: a. Inclusion criteria • Neuroendocrine tumour (histopathologcally verified). • Liver metastases on CT measurable as according to the RECIST 1.1 criteria. • No further surgical options (including radiofrequency ablation (RFA)). • Positive 111In- Octreotide scintigraphy and tumour uptake on the OctreoScan at least as high as normal liver parenchyma uptake, as judged from planar images, according to ENETS Consensus Guidelines (9) and/or positive baseline PET/CT with 68Ga-DOTATATE SUVmax for liver metastases at least as high as the SUVmax of normal liver parenchyma. • Treatment with long-acting somatostatin formulations has been stopped at least 6 weeks before PRRT, and switched to short-acting formulations up to 1 day before PRRT. • Age > 18 years. • Performance status 0-1 (39). • Informed consent obtained. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: b. Exclusion criteria (non-inclusion) • Pregnancy or lactating. • Women of childbearing potential and men who do not consent to use adequate contraception during the course of the study and 24 weeks after the last dose of protocol-specified therapy. Adequate contraceptive precautions include double barrier contraceptive methods (e.g. diaphragm and condom) or abstinence. • Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedure. • Severe co-morbidity (e.g. severe cardiac disease or AMI within 1 year of inclusion). • Impaired haematological function. Hgb. 3 x upper limit of normal or albumin <30 g/l and prothrombin time increased ((9). • Severe cardiac impairment. • Prolonged (i.e. more than 2-3 months) WHO grade 3 or 4 haematological renal or hepatic toxicity (40).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Tumour specific up-regulation of SSTR expression may be a rational approach to increase the tumour dosage and tumour to background ratio in NETs. The purpose of this trial is accordingly: 1. As a first step this investigation elucidates the induction effect on SSTRs and the possible related increase in tumour dosage and tumour to background ratio following focused external irradiation of liver metastases. ;Secondary Objective: 2. Secondly, if SSTR up-regulation is confirmed, to test the hypothesis that tumour response and therefore probably also survival, can be improved by adding induction of SSTR expression to the generally accepted best practice PRRT procedures in patient with NETs. ;Primary end point(s): Primary endpoint • Comparison between irradiated and non-irradiated patient groups for change in SSTR expression over time in liver metastases, primary tumour and extra hepatic metastases if present and in the irradiated patient group for change in SSTR expression over time in irradiated liver metastases compared to the non-irradiated primary tumour and extra hepatic metastases, if present. ;Timepoint(s) of evaluation of this end point: Interim evaluation of response is performed before each new therapeutical cycle. Final evaluation is performed after all included patients have finished all therapeutical cycles. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints • PR rate for the two therapeutical groups evaluated as the maximal response obtained following each radiotherapeutical cycle and at completion of the study. • CR rate for the two therapeutical groups evaluated after each radiotherapeutical cycle and at completion of the study. • Progression-free survival (PFS) for the two therapeutical groups evaluated according to the RECIST criteria, version 1.1 (26). • Median survival (MS for the two therapeutical groups). • 5 year survival for the two therapeutical groups. • QUALY adjusted survival for the two therapeutical groups (36-38). • Tumour response and duration of response in externally irradiated liver metastases compared to non-irradiated primary tumour and non-irradiated metastases. ;Timepoint(s) of evaluation of this end point: Interim evaluation of response is performed before each new therapeutical cycle. Final evaluation is performed after all included patients have finished all therapeutical cycles. Follow up is continued after end of therapy every 6 months for registration of PR, CR, PFS, MS, 5 year survival and QUALY adjusted survival. | — |
Countries
Denmark
Outcome results
None listed