Clinical trial • Phase III • Oncology

lutetium (177lu) edotreotide for Gastroenteropancreatic neuroendocrine tumour (GEP-NET)

Phase III trial of lutetium (177lu) edotreotide for Gastroenteropancreatic neuroendocrine tumour (GEP-NET).

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Gastroenteropancreatic neuroendocrine tumour (GEP-NET)
Trial Stage
Phase III
Drug Modality
Radiopharmaceutical | Small molecule
Orphan Drug
Yes

Key dates

Initial CTIS Submission Date
30-05-2024
First CTIS Authorization Date
25-06-2024

Trial design

Randomised, open-label, everolimus (afinitor) 10 mg orally once daily until diagnosis of progression; dose may be reduced for tolerability according to product information.-controlled Phase III trial in Austria, Germany, Poland and others.

Randomised
Yes
Open Label
Yes
Comparator
Everolimus (Afinitor) 10 mg orally once daily until diagnosis of progression; dose may be reduced for tolerability according to product information.
Target Sample Size
300
Trial Duration For Participant
2070

Eligibility

Recruits 300 Participants unable to provide meaningful informed consent themselves are excluded. Exclusion wording: "Subjects not able to declare meaningful informed consent on their own (e.g. with legal guardian for mental disorders) or any other vulnerable population to that sense (e.g. persons institutionalised, incarcerated etc.)" Written informed consent is required from each participant (see inclusion criterion 1)..

Pregnancy Exclusion
11. Pregnant or breast-feeding women
Vulnerable Population
Participants unable to provide meaningful informed consent themselves are excluded. Exclusion wording: "Subjects not able to declare meaningful informed consent on their own (e.g. with legal guardian for mental disorders) or any other vulnerable population to that sense (e.g. persons institutionalised, incarcerated etc.)" Written informed consent is required from each participant (see inclusion criterion 1).

Inclusion criteria

  • {"criterion_text":"- 1. Written informed consent\n- 2. Male or female ≥18 years of age\n- 3. Histologically confirmed diagnosis of well-differentiated neuro-endocrine tumour of non-functional gastroenteric origin (GE-NET) or both functional or non-functional pancreatic origin (P-NET)\n- 4. Measurable disease per RECIST 1.1\n- 5. Somatostatin receptor positive (SSTR+) disease\n- 6. Progressive disease based on RECIST 1.1. criteria as evidenced by two morphological imaging examinations made with the same imaging method (either CT or MRI)"}

Exclusion criteria

  • {"criterion_text":"- 1. Known hypersensitivity to edotreotide or everolimus\n- 10. Clinically relevant renal, hepatic, cardiovascular, or haematological organ dysfunction, potentially interfering with the safety of the study treatments\n- 11. Pregnant or breast-feeding women\n- 12. Subjects not able to declare meaningful informed consent on their own (e.g. with legal guardian for mental disorders) or any other vulnerable population to that sense (e.g. persons institutionalised, incarcerated etc.)\n- 2. Known hypersensitivity to DOTA, lutetium-177, or any excipient of edotreotide or everolimus or any other Rapamycin derivative.\n- 3. Prior exposure to any peptide receptor radionuclide therapy (PRRT)\n- 4. Prior therapy with mTor inhibitors\n- 5. Prior EFR (external field radiation) to GEP-NET lesions within 90 days before randomisation or radioembolisation therapy.\n- 6. Therapy with an investigational compound and/or medical device within 30 days prior to randomization\n- 7. Indication for surgical lesion removal with curative potential\n- 8. Planned alternative therapy (for the period of study participation)\n- 9. Serious non-malignant disease"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- 1. Progression-free survival (PFS)","definition_or_measurement_approach":""}

Secondary endpoints

  • {"endpoint_text":"- 1. Objective response rate (ORR), % patients achieving PR or CR as best outcome\n- 2. Overall survival (OS)\n- 3. Safety and tolerability-Measured TER, percentage depart from baseline value\n- 4. Safety and tolerability-Calculated GFR, percentage depart from baseline value\n- 5. Safety and tolerability-Renal volume (Vkidney), percentage depart from baseline value\n- 6. Safety and tolerability-Frequency of occurrence and severity of abnormal findings in safety investigations (vital signs, 12-lead ECG, clinical laboratory, adverse events)\n- 7. Health-related quality of life (HRQL)- Maximum HRQL improvement (EORTC QLQ-C30 and GI.NET21 questionnaires) total scores, relative to baseline\n- 8. Health-related quality of life (HRQL)- Duration of maximum HRQL improvement\n- 9. Health-related quality of life (HRQL)- Time to HRQL deterioration, defined as the time from randomisation to first HRQL deterioration\n- 10. Dosimetry- Full dosimetry assessments of target organs and tumour lesions\n- 11. Dosimetry- Cumulative absorbed dose (in Gy) from 177Lu-edotreotide to target tumour lesions, estimated from 177Lu-edotreotide dosimetry after first dose\n- 12. Dosimetry- Sub-study A patients: cumulative absorbed dose to kidneys and to tumour lesions extrapolated from absorbed dose estimated at D1 compared with the cumulative absorbed dose measured at the different administration times (i.e. D1 to D4)\n- 13. Dosimetry- Sub-study B patients: absorbed dose (in Gy) determined by 3D dosimetry compared to absorbed dose values obtained by planar (2D) and hybrid (2D/3D) dosimetry\n- 14. Dosimetry- Sub-study C patients: bone marrow absorbed dose (in Gy) extrapolated from blood radioactivity\n- 15. Pharmacokinetics (Sub-study C) Urine radioactivity in percentage of injected activity (%IA) at pre-defined intervals within 48 hours post-injection to assess excretion pattern\n- 16. Pharmacokinetics (Sub-study C) Blood radioactivity in %IA at pre-defined time points within 7 days post-injection to assess clearance pattern\n- 17. Pharmacokinetics (Sub-study C)_Radiochemical purity assessed through HPLC of urine samples collected within 48 hours post-injection","definition_or_measurement_approach":"- ORR: defined as the proportion of patients achieving partial response (PR) or complete response (CR) as best outcome (explicitly stated in objectives).\n- OS: defined as the time from the date of randomisation until death (explicitly stated).\n- HRQL endpoints: measured using EORTC QLQ-C30 and GI.NET21 questionnaires (explicitly stated).\n- Dosimetry and pharmacokinetics: defined by protocol sub-studies (full dosimetry assessments, cumulative absorbed dose in Gy, 3D vs 2D dosimetry comparisons, bone marrow dose extrapolated from blood radioactivity, urine and blood %IA at defined intervals, radiochemical purity by HPLC) as described in endpoint listings."}

Recruitment

Planned Sample Size
300
Recruitment Window Months
131
Consent Approach
Written informed consent required from each participant (inclusion criterion: "1. Written informed consent"). Participants must be ≥18 years old. Inability to provide meaningful informed consent (e.g. requiring a legal guardian) is an exclusion. Subject information and consent forms (L1_SIS and ICF) and lay synopses are available in multiple country/language versions (documents exist in German, French, Spanish, Polish, Dutch, Italian, Czech and language variants for BE/NL/FR), and a re-consent document is available.

Geography

Total Number Of Sites
33
Total Number Of Participants
268

Austria

Earliest CTIS Part Ii Submission Date
18-06-2024
Latest Decision Or Authorization Date
03-07-2024
Processing Time Days
15
Number Of Sites
1
Number Of Participants
2

Sites

Site Name
Medical University Of Vienna
Department Name
Nuclear Medicine
Contact Person Name
Marcus Hacker
Contact Person Email
nuk@meduniwien.ac.at

Germany

Earliest CTIS Part Ii Submission Date
18-06-2024
Latest Decision Or Authorization Date
27-06-2024
Processing Time Days
9
Number Of Sites
11
Number Of Participants
57

Sites

Site Name
Universitaetsklinikum Giessen und Marburg GmbH (Marburg)
Department Name
Nuclear Medicine
Contact Person Name
Anja Rinke
Contact Person Email
gastro@med.uni-marburg.de
Site Name
Universitaetsklinikum Ulm AöR
Department Name
Nuclear Medicine
Contact Person Name
Thomas Ettrich
Site Name
Universitaetsklinikum Bonn AöR
Department Name
Nuclear Medicine
Contact Person Name
Markus Essler
Site Name
Universitaetsklinikum Erlangen AöR
Department Name
Nuclear Medicine
Contact Person Name
Marianne Pavel
Contact Person Email
marianne.pavel@uk-erlangen.de
Site Name
Charite Universitaetsmedizin Berlin KöR
Department Name
Nuclear Medicine
Contact Person Name
Peter Richard Steinhagen
Contact Person Email
peter.steinhagen@charite.de
Site Name
Klinikum rechts der Isar der TU Muenchen AöR
Department Name
Nuclear Medicine
Contact Person Name
Wolfgang Weber
Contact Person Email
nukmed.sekretariat@mri.tum.de
Site Name
Universitaetsklinikum Essen AöR
Department Name
Nuclear Medicine
Contact Person Name
Ken Herrmann
Site Name
Zentralklinik Bad Berka GmbH
Department Name
Nuclear Medicine
Contact Person Name
Dieter Hörsch
Contact Person Email
nuk@zentralklinik.de
Site Name
Universitaetsklinikum Wuerzburg AöR
Department Name
Nuclear Medicine
Contact Person Name
Andreas Buck
Contact Person Email
buck_a@ukw.de
Site Name
Universitaetsklinikum Magdeburg AöR
Department Name
Nuclear Medicine
Contact Person Name
Michael Kreißl
Contact Person Email
michael.kreissl@med.ovgu.de
Site Name
University Medical Center Hamburg-Eppendorf
Department Name
Nuclear Medicine
Contact Person Name
Ivayla Apostolova
Contact Person Email
i.apostolova@amsterdamumc.nl

Poland

Earliest CTIS Part Ii Submission Date
01-07-2024
Latest Decision Or Authorization Date
22-07-2024
Processing Time Days
21
Number Of Sites
2
Number Of Participants
12

Sites

Site Name
Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
Department Name
Zakład Medycyny Nuklearnej i Endokrynologii Onkologicznej
Contact Person Name
Daria Handkiewicz - Junak
Contact Person Email
onkologia@io.gliwice.pl
Site Name
"GAMMED" IZABELA CHUCHROWSKA
Department Name
Centrum Diagnostyczno-Lecznicze "GAMMED"
Contact Person Name
Jarosław Ćwikła
Contact Person Email
gammed@poczta.fm

Netherlands

Earliest CTIS Part Ii Submission Date
18-06-2024
Latest Decision Or Authorization Date
25-06-2024
Processing Time Days
7
Number Of Sites
1
Number Of Participants
10

Sites

Site Name
Amsterdam UMC Stichting
Department Name
Oncology
Contact Person Name
J.W. Wilmink
Contact Person Email
j.w.wilmink@amsterdamumc.nl

Spain

Earliest CTIS Part Ii Submission Date
18-06-2024
Latest Decision Or Authorization Date
16-07-2024
Processing Time Days
28
Number Of Sites
5
Number Of Participants
70

Sites

Site Name
Hospital Universitario Y Politecnico La Fe
Department Name
Endocrinology Service
Contact Person Name
Maria Isabel Del Olmo Garcia
Contact Person Email
maribeldelolmo@gmail.com
Site Name
Institut Catala D'oncologia
Department Name
Oncology Service
Contact Person Name
Alexandre Teule Vega
Contact Person Email
ateule@iconcologia.net
Site Name
Hospital Universitario Central De Asturias
Department Name
Medical Oncology
Contact Person Name
Paula Jimenez-Fonseca
Contact Person Email
palucaji@hotmail.com
Site Name
Hospital Universitario 12 De Octubre
Department Name
Medical Oncology
Contact Person Name
Rocio Garcia-Carbonero
Contact Person Email
rgcarbonero@gmail.com
Site Name
Hospital Universitari Vall D Hebron
Department Name
Medical Oncology Department
Contact Person Name
Jaume Capdevila
Contact Person Email
comunicacio.imatge@vhebron.net

France

Earliest CTIS Part Ii Submission Date
18-06-2024
Latest Decision Or Authorization Date
28-06-2024
Processing Time Days
10
Number Of Sites
6
Number Of Participants
93

Sites

Site Name
Hopital Beaujon
Department Name
Gastroentérologie Pancréatologie/ Médecine Nucléaire
Contact Person Name
Louis de Mestier du Bourg
Contact Person Email
louis.demestier@aphp.fr
Site Name
Centre Jean Perrin
Department Name
Médecine Nucléaire/ Hépato-Gastro-Entérologie
Contact Person Name
Antony Kelly
Site Name
Centre Hospitalier Universitaire De Nantes
Department Name
Médecine Nucléaire/ Hépato-gastro-entérologie et oncologie digestive
Contact Person Name
Catherine Ansquer
Site Name
Hospital Edouard Herriot
Department Name
Hépato-Gastro-Entérologie/Médecine Nucléaire
Contact Person Name
Thomas Walter
Contact Person Email
thomas.walter@chu-lyon.fr
Site Name
Institut Universitaire Du Cancer Toulouse-Oncopole
Department Name
Médecine Nucléaire/Oncologie Médicale Digestive
Contact Person Name
Lawrence Dierickx
Site Name
Institut Regional Du Cancer De Montpellier
Department Name
Médecine Nucléaire/ Oncologie Digestive
Contact Person Name
Emmanuel Deshayes

Italy

Earliest CTIS Part Ii Submission Date
18-06-2024
Latest Decision Or Authorization Date
01-07-2024
Processing Time Days
13
Number Of Sites
3
Number Of Participants
13

Sites

Site Name
Fondazione IRCCS Istituto Nazionale Dei Tumori
Department Name
Nuclear Medicine
Contact Person Name
Marco Maccauro
Site Name
European Institute Of Oncology S.r.l.
Department Name
Nuclear Medicine
Contact Person Name
Chiara Maria Grana
Contact Person Email
chiara.grana@ieo.it
Site Name
Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.
Department Name
Nuclear Medicine
Contact Person Name
Maddalena Sansovini
Contact Person Email
info@irst.emr.it

Czechia

Earliest CTIS Part Ii Submission Date
18-06-2024
Latest Decision Or Authorization Date
01-07-2024
Processing Time Days
13
Number Of Sites
2
Number Of Participants
6

Sites

Site Name
Fakultni Nemocnice V Motole
Department Name
Onkologická klinika 2.LF UK a FN Motol
Contact Person Name
Kateřina Kopečková
Contact Person Email
studie@fnmotol.cz
Site Name
University Hospital Olomouc
Department Name
Klinika nukleární medicíny
Contact Person Name
Pavel Koranda
Contact Person Email
pavel.koranda@fnol.cz

Belgium

Earliest CTIS Part Ii Submission Date
18-06-2024
Latest Decision Or Authorization Date
27-06-2024
Processing Time Days
9
Number Of Sites
2
Number Of Participants
5

Sites

Site Name
Institut Jules Bordet
Department Name
Nuclear medicine
Contact Person Name
Ioannis Karfis
Contact Person Email
ioannis.karfis@hubruxelles.be
Site Name
UZ Leuven
Department Name
Nuclear medicine
Contact Person Name
Christophe Deroose
Contact Person Email
christophe.deroose@uzleuven.be

Sponsor

Primary sponsor

Full Name
ITM Solucin GmbH
Organisation Type
Pharmaceutical company
Country Of Registered Address
Germany

Contract research organisations

Name
ABX CRO advanced pharmaceutical services Forschungsgesellschaft mbH
Responsibilities
Medical image analysis
Name
Psi Cro AG

Third parties

  • {"country":"Germany","full_name":"ABX CRO advanced pharmaceutical services Forschungsgesellschaft mbH","duties_or_roles":"Medical image analysis","organisation_type":"Pharmaceutical company"}
  • {"country":"Spain","full_name":"Asphalion S.L.","duties_or_roles":"Pharmacovigilance","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"Promedim","duties_or_roles":"Medical Monitoring","organisation_type":"Industry"}
  • {"country":"Germany","full_name":"ABX CRO advanced pharmaceutical services Forschungsgesellschaft mbH","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"Switzerland","full_name":"Psi Cro AG","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"Bionical-EMAS","duties_or_roles":"Medical Monitoring","organisation_type":"Industry"}
  • {"country":"Switzerland","full_name":"Inselspital University Hospital Bern","duties_or_roles":"Histopathology","organisation_type":"Hospital/Clinic/Other health care facility"}
  • {"country":"Canada","full_name":"Centre for Probe Development and Commercialization, Tandem Accelerator Building, McMaster University","duties_or_roles":"manufacturing of 177-Lu-Edotreotide","organisation_type":"Industry"}
  • {"country":"Germany","full_name":"FORMULA Pharmazeutische Produkte GmbH","duties_or_roles":"manufacturing Everolimus (packaging, labeling)(","organisation_type":"Pharmaceutical company"}
  • {"country":"Belgium","full_name":"Cerba Research","duties_or_roles":"urine and blood analysis","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"Austria","full_name":"Seibersdorf Labor GmbH","duties_or_roles":"Manufacturing 177Lu-Edotreotide","organisation_type":"Pharmaceutical company"}
  • {"country":"Germany","full_name":"Nuvisan GmbH","duties_or_roles":"Analytical chemistry, Parent- metabolite ratio analysis in urine","organisation_type":"Pharmaceutical company"}
  • {"country":"Germany","full_name":"Universitaetsklinikum Erlangen AöR","duties_or_roles":"manufacturing of nephroprotective amino acid","organisation_type":"Hospital/Clinic/Other health care facility"}

Investigational products

Investigational Product Name
177Lu-Edotreotide
Active Substance
lutetium (177lu) edotreotide
Modality
Radiopharmaceutical
Routes Of Administration
INTRAVENOUS USE
Route
Intravenous infusion
Orphan Designation
Yes
Starting Dose
7.5 GBq
Dose Levels
7.5 ± 0.7 GBq per cycle, up to 4 cycles
Frequency
Every 3 months (3-monthly intervals) up to 9 months (maximum of four cycles)
Maximum Dose
30 GBq
Investigational Product Name
Afinitor (everolimus) 10 mg tablets
Active Substance
everolimus
Modality
Small molecule
Routes Of Administration
ORAL USE
Route
Oral tablet
Authorisation Status
Marketing authorisation (EU) (marketingAuthNumber: EU/1/09/538/003 or /004 indicated)
Starting Dose
10 mg daily
Dose Levels
10 mg daily; dose reductions permitted for tolerability per product information
Frequency
Once daily
Maximum Dose
10 mg daily
Investigational Product Name
Arginine-Lysine solution for infusion
Active Substance
L-LYSINE HYDROCHLORIDE, L-ARGININE HYDROCHLORIDE
Modality
Other
Routes Of Administration
INTRAVENOUS USE
Route
Intravenous infusion
Maximum Dose
2000 ml
Combination Treatment
Yes

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