Patients with proved progressive (or refractory to standard systemic therapy available in Belgium at the time of inclusion) neuroendocrine tumors, not amenable to surgical resection with curative intent. MedDRA version: 21.0 Level: LLT Classification code 10062476 Term: Neuroendocrine tumor System Organ Class: 100000004864
Conditions
Interventions
Product Name: 177Lu-DOTATATE
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: No INN
Current Sponsor code: 177Lu_DOTATATE_IJB
Other descriptive name: LUTETIUM(177LU)-DOTA-(TYR3)-OCTREOT
Sponsors
Jules Bordet Institute
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria: Patient-based 1. Age above or equal to 18 years. 2. Histology-proven advanced GEP-NETs. 3. Disease progression defined as follows (at least one of the following): - Radiological disease progression (according to RECIST 1.1) on an MRI or CT over the last 12 months Or - Disease progression on a somatostatin receptor-imaging, PET/CT or SPECT/CT over the last 12 months [apparition of new lesion(s) or increase in the transaxial plane diameter of more than 30% on the same imaging modality] Or - Both of the following criteria (a+b): a. clinical progression: - sustained (for more than 2 weeks) increase of NET-specific hormonal hypersecretion related symptom frequency by 50% or, - sustained (for more than 2 weeks) increase of severity by 1 grade (according to NCI-CTCAE version 4.03). b. biochemical progression: by increase of NET-specific tumor markers (plasma Chromogranin A, plasma NSE, urine 5-HIAA or other) in two successive measurements. 4. Disease refractory to SSA’s and/or standard systemic therapy available in Belgium at the time of inclusion criteria. 5. Long-acting SSAs should be discontinued at least 4 weeks before study treatment start date and, if needed, switched to short-acting analogues which should be stopped 48h before the treatment date. 6. Adequate renal function with GFR = 50 mL/min/1.73m2 (evaluated by 51Cr-EDTA test). 7. Adequate bone marrow function with hemoglobin = 9 g/dL; neutrophil = 1.5·103/µL; platelet count = 100·103/µL. 8. Adequate liver function with total bilirubin = 2 x ULN and transaminases = 5 x ULN, serum albumin > 3 g/dL with normal prothrombin time (> 70%). 9. ECOG Performance Status = 1. 10. Women of childbearing potential and men with partners of childbearing potential must agree to use a highly-effective form of contraception for the duration of study participation and up to six months after the end of the treatment. A pregnancy test (serum) must be performed within 4 weeks prior to inclusion for every female patient of childbearing potential and it must be negative. 11. Patient’s written informed consent obtained prior to any study procedure. 12. All necessary baseline procedures should be performed within 4 weeks prior to first 177Lu-octreotate injection (D0). Inclusion Criteria: Lesion-based 13. The patient must have at least one target lesion fulfilling all of the below criteria: • On the 68Ga-octreotate PET/CT: tumor uptake higher than the physiological liver uptake (grade III or IV of the Rotterdam visual score30) in a lesion with longest transaxial plane diameter = 20mm (measured on the CT, part of the PET/CT); • At least one of these lesions morphologically measurable according to RECIST 1.1 and progressive on the MRI (or CT if MRI is not applicable); • Target lesion shall not have been previously irradiated. 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 26 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 26
Exclusion criteria
Exclusion criteria: 1. Resectable tumor with curative intent. 2. Any major surgery within the last 6 weeks prior to inclusion in the study 3. Radiotherapy, chemotherapy, embolization, mammalian target of rapamycin (mTOR)-inhibitors, receptor tyrosine-kinase inhibitors, interferon, or other investigational therapy within the last 12 weeks prior to inclusion in the study. 4. Diffuse bone marrow infiltration on the baseline 68Ga-octreotate PET/CT confirmed by MRI. 5. Prior external beam radiotherapy on kidneys or on more than 25% of bone marrow. 6. Patients with known uncontrolled brain metastases. 7. Patients with a significant medical, neuro-psychiatric, or surgical condition, currently uncontrolled by treatment, which, in the investigator’s opinion, may interfere with completion of the study. 8. Pregnant or lactating patients. 9. Women of childbearing potential and men with partners of child-bearing potential refusing an adequate contraception.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: For each lesion: To assess the value of the following parameters (obtained through functional and molecular imaging) for predicting the lesion-by-lesion PRRT treatment outcome: - 18FDG uptake on 18FDG PET/CT, - 68Ga-octreotate uptake on 68Ga-octreotate PET/CT, - Apparent Diffusion Coefficient on Diffusion Weighted-MRI, [for these three parameters, absolute values at baseline will be assessed] - Tumor dosimetry on post-177Lu-octreotate SPECT/CT after the first cycle.;Secondary Objective: Secondary objective: To generate a patient-based response model based on the previously defined parameters. Exploratory objectives: For each lesion: to assess the value of the parameters mentioned in section 3.1 for predicting the lesion-by-lesion PRRT treatment outcome: - absolute values of the three imaging parameters and their relative changes after each cycle; - serial tumor dosimetry on post-177Lu-octreotate SPECT/CT after each cycle;Primary end point(s): The time to progression (TTP) for each target lesion assessed on MRI (or on CT scan if MRI is not applicable). TTP is defined as the time between treatment initiation and objective tumor progression with censoring of patients who die as a result of any cause. Progression is defined in the Treatment Modalities paragraph.;Timepoint(s) of evaluation of this end point: After morphological progression of the patient (according to RECIST 1.1) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints: • Best morphological response according to RECIST 1.1, • Progression Free Survival (PFS). PFS is defined as the time between treatment initiation and the first of the following events: disease progression (clinical or radiological) or death resulting from any cause. Progression is defined in the Treatment Modalities paragraph. • Biochemical response (evolution of NET-specific tumoral markers, as for inclusion). Exploratory endpoints: The time to progression (TTP) for each target lesion assessed on MRI (or on CT scan if MRI is not applicable). Progression is defined in the Treatment Modalities paragraph.;Timepoint(s) of evaluation of this end point: For the secondary endpoint: After morphological progression of the patient (according to RECIST 1.1) For the exploratory endpoints: After each cycle of treatment | — |
Countries
Belgium
Contacts
Public ContactIoannis Karfis
Jules Bordet Institute
Outcome results
None listed