Patients with inoperable, progressive, somatostatin receptor-positive(SSTR+), neuroendocrine tumours of gastroenteric or pancreatic origin (GEP-NET) MedDRA version: 20.0 Level: PT Classification code 10077559 Term: Gastroenteropancreatic neuroendocrine tumour disease System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: 177Lu-Edotreotide
Product Code: 177Lu-DOTATOC
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: 177Lu-Edotreotide
CAS Number: 321835-55-6
Other descriptive name: 177LU-EDOT
Sponsors
ITM Solucin GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: All patients must meet all of the following criteria: 1. Written informed consent 2. Male or female = 18 years of age 3. Histologically confirmed diagnosis of well-differentiated neuroendocrine tumour of non-functional gastroenteric origin (GE-NET) or both functional or non-functional pancreatic origin (P-NET), tumour grade G1 or G2 (Ki-67 =65 years) yes F.1.3.1 Number of subjects for this age range 100
Exclusion criteria
Exclusion criteria: A patient will be excluded from participation in the trial if one or more of the following criteria are met: 1. Known hypersensitivity to edotreotide or everolimus 2. Known hypersensitivity to DOTA, lutetium-177, or any excipient of edotreotide or everolimus or any other Rapamycin derivative 3. Known hypersensitivity to lysine, arginine, or any excipient of the nephroprotective amino acid solution 4. Prior exposure to any peptide receptor radionuclide therapy (PRRT), including 177Lu-edotreotide, 90Y-edotreotide or other SSTR-targeting agents (e.g. 177Lu-octreotate or high-dose 111In-pentetreotide) 5. Prior therapy with mTOR inhibitors 6. Prior EFR (external field radiation) to GEP-NET lesions within 90 days before randomization or radioembolisation therapy (e.g. 90Y microspheres, 131I-lipiodol) with administration to the liver 7. Prior therapy with chemotherapy, immunotherapy, interferon, chemo-embolisation, bland embolisation, cyclosporine-A within 4 weeks before randomisation; any new cancer treatment between screening and randomisation 8. Therapy with an investigational compound and/or medical device within 30 days or 5 half-life periods (whichever is longer) prior to randomisation 9. Subjects who have received a live vaccine up to 4 weeks prior to first dose 10. Current therapy with any prohibited medication (see 6.1.1) 11. Ongoing toxicity grade 2 according to CTCAE version 4.03 from previous standard or investigational therapies 12. Indication for surgical lesion removal with curative potential 13. Planned (for the period of study participation): chemotherapy, immunotherapy, interferon, radiation therapy, chemo-embolisation, bland embolisation, radio-embolisation, treatment with cyclosporine-A 14. Neuroendocrine tumours, not meeting the inclusion criteria: • With known non-GEP-NET origin (e.g. pulmonary or gonadal primaries) • Functional GE-NET • Explicit diagnosis of unknown primary (CUP) • G3 neuroendocrine tumours and neuroendocrine carcinomas • NET for which no histological specimen for secondary histological analysis can be obtained 15. Total hepatic tumour burden > 70% 16. Brain metastases 17. Other malignancy within previous 5 years (except basal cell carcinomas and in situ squamous cell carcinomas of the skin) 18. Serious non-malignant disease (e.g. psychiatric, infectious, autoimmune or metabolic), that may interfere with the objectives of the study or with the safety or compliance of the subject, as judged by the investigator 19.Clinically relevant renal, hepatic, cardiovascular, or haematological organ dysfunction, potentially interfering with the safety of the study treatments, as follows: • Renal o Renal obstruction Hepatic o Total bilirubin >1.5 x ULN o AST or ALT >2.5 x ULN o Alkaline phosphatase >5 x ULN o Albumin <3 g/dL, unless prothrombin time is within normal range • Cardiovascular o New York Heart Association classification III and IV o Uncontrolled hypertension • Haematopoietic o Platelets =80 × 109/L o Absolute neutrophil count (ANC) <1 x 109 cells/L 20.Pregnant or breast-feeding women. Female patients of childbearing potential or male patients with female partners of childbearing potential, unless willing to practice full and true sexual abstinence or who are being surgically/permanently sterile (bilateral tubal occlusion, hysterectomy, or vasectomy), or female patients whose male partners have medically successful vasectomy (provided the partner is the sole sexual partner of the female patient of childbe
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate the efficacy of PRRT with 177Lu-edotreotide to prolong progression-free survival (mPFS) in patients with inoperable, progressive, SSTR+ GEP-NET, compared to everolimus;Secondary Objective: 1. To assess objective response rates (ORR), defined as the proportion of patients achieving partial response (PR) or complete response (CR) as best outcome after treatment with 177Lu-edotreotide vs. everolimus 2. To assess overall survival (OS), defined as the time from date of randomisation until death Exploratory secondary objectives: 3. To assess duration of disease control (DDC) defined as the time of initial diagnosis of response (SD, PR or CR) until diagnosis of progression, after treatment with 177Lu-edotreotide vs. everolimus 4. To determine disease control rates (DCR) 5. To determine response rates (RR) 6. To assess the safety and tolerability of 177Lu-edotreotide in GEP-NET patients 7. To determine the health-related quality of life (HRQL) in GEP-NET patients during and after therapy 8. To evaluate symptomatic tumour response 9. To evaluate the impact of patient characteristics on tumor response 10. To evaluate the impact of tumour histology on tumor response ;Primary end point(s): The primary endpoint is progression-free survival (PFS). Diagnosis of progression and liver tumour burden will be established based on radiological information from morphological imaging (MRI and/or CT) according to RECIST 1.1. Stratification will be made for primary tumour origin (GE-NET vs. P-NET) and prior medical therapy (1st line vs. 2nd line). Tumour grade (G1, G2), and baseline Karnofsky score will be used for further statistical subgroup analyses.;Timepoint(s) of evaluation of this end point: Progression-free survival (PFS) will be determined as time elapsed between randomisation, and the date of first objective report of tumour progression (evaluated by RECIST criteria, 1.1), or death. Diagnosis of Progression will be established based on radiological I | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints include parameters of morphological and functional tumour response, such as objective response rate (ORR), overall survival (OS) , disease control rates (DCR), and duration of disease control (DDC), as well as safety, health-related quality of life (HRQL).Furthermore, exploratory analyses will be performed on patient and tumour characteristics, as well as the degree of 177Lu-edotreotide uptake as possible predictors of PRRT efficacy.;Timepoint(s) of evaluation of this end point: At the end of study | — |
Countries
Australia, Austria, Belgium, Czechia, Czech Republic, France, Germany, Italy, Netherlands, Poland, South Africa, Spain, Switzerland, United Kingdom, United States
Contacts
Public ContactTim Hammer
ABX-CRO advanced pharmaceutical services mbH
Outcome results
None listed