Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ongoing, recruiting
Participants planned
23
Countries
1
Sites
5
Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) in adults
68Ga-DOTA-peptides uptake (SUVmax) in up to 5 liver metastases on PET-scan obtained after intra-hepatic radiolabeled somatostatin analogs (SSA) infusion and on PET-scan obtained after intravenous radiolabeled SSA administration
Key facts
- Sponsor
- Centre Hospitalier Universitaire De Bordeaux
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01], Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutics [E02]
- Trial duration
- 24 Sep 2021 → ongoing
- Decision date (initial)
- 2024-11-04
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- Programme Hospitalier de Recherche Clinique Inter régional 2017 (PHRC I 2017)
External identifiers
- EU CT number
- 2024-514785-39-00
- EudraCT number
- 2019-003023-38
- ClinicalTrials.gov
- NCT04837885
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy, Safety, Diagnosis, Efficacy
68Ga-DOTA-peptides uptake (SUVmax) in up to 5 liver metastases on PET-scan obtained after intra-hepatic radiolabeled somatostatin analogs
(SSA) infusion and on PET-scan obtained after intravenous radiolabeled SSA administration
Secondary objectives 5
- Safety profile : safety of 177Lu-DOTA-peptide after intra-arterial hepatic administration
- 68Ga-DOTA-peptide uptake (SUVmax) on dose limiting organs (kidney, spleen, healthy liver, bone marrow) after 68Ga-DOTA-peptides by arterial intrahepatic and intravenous injections
- 68Ga-DOTA-peptide uptake (SUVmax) on extra-hepatic lesion after 68Ga-DOTA-peptides by arterial intrahepatic and intravenous injections
- Estimate the lesional and organ (kidney, spleen, healthy liver, bone marrow) absorbed doses after 177Lu-DOTA-peptide administration by intra-arterial hepatic and intravenous injections
- Efficacy evaluation of the fifth cycle of 177Lu-DOTA-peptide therapy administered by intra-arterial hepatic infusion according to RECIST1.1 criteria
Conditions and MedDRA coding
Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) in adults
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | LLT | 10077560 | Gastroenteropancreatic neuroendocrine tumor disease | 10029104 |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 11
- Histologically proven well differentiated neuroendocrine tumor (NET) of gastrointestinal or pancreatic origin (GEP)
- Liver Metastatic disease dominant or exclusive and assessable by RECIST 1.1, and not amenable to surgical resection after the 4 cycles
- Patients are progressive after treatment with cold somatostatin analog (within 12 months according to RECIST), or as soon as the diagnosis is made in case of hepatic invasion > 50% without waiting for tumour progression
- Patient has received 4 standard of care LUTATHERA® cycles
- ECOG performance status 0-2
- Adequate kidney and liver function: creatinine clearance ≥ 50 mL/min, ALT/AST ≤ 2,5x the upper limit of normal
- With no evidence of hematologic alteration after 4 LUTATHERA® cycles: hemoglobin ≥ 8 g/dL, neutrophils ≥ 1500/ mm3, platelets ≥ 75.000/mm3
- Age ≥ 18 years, no superior limit
- Highly effective contraception for women of childbearing potential (Intrauterine device, Progestin Pills, Combined Oral Contraceptives, Monthly Injectables, Progestin Injectables, Combined Patch, Combined Vaginal Ring, Female Sterilization, Vasectomised partner, sexual abstinence, Implant). Contraception for men (condom) or their sexual partner (effective contraception) (CTFG recommandations : https://www.hma.eu/fileadmin/dateien/Human_Medicines/01- About_HMA/Working_Groups/CTFG/2020_09_HMA_CTFG_Contraceptio n_guidance_Version_1.1_updated.pdf). Contraception must be maintained for at least 7 months after the last LUTATHERA ® injection for women with childbearing capacity and at least 4 months for men who have female partners with childbearing capacity
- Patient´s signed written informed consent
- Patient affiliated to a social security system
Exclusion criteria 12
- Patients with complete response defined by the absence of lesion according to RECIST 1.1 realized during morphological imaging at inclusion (chest-abdomen-pelvis CT scan and hepatic MRI)
- Or no residual uptake according to standard 177-Lu tomoscintigraphy performed in the clinical routine 24 hours after the last LUTATHERA IV treatment
- Carcinoid heart disease (LVEF < 40%)
- Dominant or threatening extrahepatic metastases or that may affect vital prognosis
- Contraindications to intra-hepatic arterial infusion (coagulation disorders, portal thrombosis, intra-hepatic biliary tract dilatation, digestive or biliary anastomosis or fistula, cirrhosis (Child Pugh B8 or C…)
- Serum albumin <30 g/L unless prothrombin time is within the normal range.
- Heart failure, myocardial infarction, stroke, uncontrolled arterial hypertension under optimal treatment (≥ 160/95 mmHg), pulmonary embolism or revascularization procedure, unstable angina pectoris, uncontrolled cardiac arrhythmia, and clinically significant bradycardia during the last 12 months.
- Pregnancy or breast feeding
- Currently participating to another category 1 or 2 clinical research protocol
- Individuals under legal protection or unable of giving their informed consent
- MRI scan contraindicated
- LUTATHERA® contraindicated or toxicity during one of the IV administrations leading to a reduction or cancellation of the following dose
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- 68Ga-DOTA-peptides uptake (Maximum Standardized Uptake Value) in up to 5 liver metastases on PET-scan obtained after intra-hepatic injection
Secondary endpoints 5
- Safety profile : safety of 177Lu-DOTA-peptide after intra-arterial hepatic administration
- 68Ga-DOTA-peptide uptake (SUVmax) on dose limiting organs (kidney, spleen, healthy liver, bone marrow) after 68Ga-DOTA-peptides by arterial intrahepatic and intravenous injections
- 68Ga-DOTA-peptide uptake (SUVmax) on extra-hepatic lesion (if present) after 68Ga-DOTA-peptides by arterial intrahepatic and intravenous injections
- Estimate the lesional and organ (kidney, spleen, healthy liver, bone marrow) absorbed doses after 177Lu-DOTA-peptide administration by intra-arterial hepatic and intravenous injections
- Efficacy evaluation of the fifth cycle of 177Lu-DOTA-peptide therapy administered by intra-arterial hepatic infusion according to RECIST1.1 criteria
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 2
Lutathera 370 MBq/mL solution for infusion
PRD5434501 · Product
- Active substance
- Lutetium (177LU) Oxodotreotide
- Substance synonyms
- 177LU-DOTA-TYR3-OCTREOTATE, 177LU-DOTA0-TYR3-OCTREOTATE, 177LU-DOTATATE, DOTATATE LUTENIUM LU-177, LUTETIUM (177LU) DOTATATE, LUTETIUM (177LU)-N-[(4,7,10-TRICARBOXYMETHYL-1,4,7,10-TETRAAZACYCLODODEC-1-YL)ACETYL]-D-PHENYLALANYL-L-CYSTEINYL-L-TYROSYL-D-TRYPTOPHANYL-L-LYSYL-L-THREONINYL-L-CYSTEINYL-L-THREONINE-CYCLIC(2-7)DISULPHIDE
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAARTERIAL USE
- Max daily dose
- 370 MBq/ml megabecquerel(s)/millilitre
- Max total dose
- 370 MBq/ml megabecquerel(s)/millilitre
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- V10XX04 — -
- Marketing authorisation
- EU/1/17/1226/001
- MA holder
- ADVANCED ACCELERATOR APPLICATIONS
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- Yes
- Orphan designation number
- EU/3/07/523
- Modified vs. Marketing Authorisation
- No
SomaKit TOC 40 micrograms kit for radiopharmaceutical preparation
PRD4592308 · Product
- Active substance
- Edotreotide
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAARTERIAL USE
- Max daily dose
- 200 MBq megabecquerel(s)
- Max total dose
- 200 MBq megabecquerel(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- V09IX09 — -
- Marketing authorisation
- EU/1/16/1141/001
- MA holder
- ADVANCED ACCELERATOR APPLICATIONS
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- Yes
- Orphan designation number
- EU/3/15/1450
- Modified vs. Marketing Authorisation
- No
Auxiliary 9
LASILIX 40 mg, comprimé sécable
PRD430161 · Product
- Active substance
- Furosemide
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 60 mg milligram(s)
- Max total dose
- 60 mg milligram(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- C03CA01 — FUROSEMIDE
- Marketing authorisation
- 34009 372 377 9 6
- MA holder
- SANOFI WINTHROP INDUSTRIE
- MA country
- France
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
ZOPHREN 8 mg, comprimé pelliculé
PRD10107630 · Product
- Active substance
- Ondansetron Hydrochloride Dihydrate
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 8 mg milligram(s)
- Max total dose
- 40 mg milligram(s)
- Max treatment duration
- 5 Day(s)
- Authorisation status
- Authorised
- ATC code
- A04AA01 — ONDANSETRON
- Marketing authorisation
- 34009 335 387 4 3
- MA holder
- SANDOZ
- MA country
- France
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD10009789 · Product
- Active substance
- Amlodipine Besilate
- Pharmaceutical form
- CAPSULE, HARD
- Route of administration
- ORAL USE
- Max daily dose
- 10 mg milligram(s)
- Max total dose
- 50 mg milligram(s)
- Max treatment duration
- 5 Day(s)
- Authorisation status
- Authorised
- ATC code
- C08CA01 — AMLODIPINE
- Marketing authorisation
- 34009 372 438 8 9
- MA holder
- VIATRIS UP
- MA country
- France
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
HYDROXYZINE RENAUDIN 100 mg/2 mL, solution injectable
PRD2902926 · Product
- Active substance
- Hydroxyzine Hydrochloride
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SOLUTION FOR INFUSION
- Max daily dose
- 100 mg milligram(s)
- Max total dose
- 500 mg milligram(s)
- Max treatment duration
- 5 Week(s)
- Authorisation status
- Authorised
- ATC code
- N05BB01 — HYDROXYZINE
- Marketing authorisation
- 34009 361 356 5 9
- MA holder
- LABORATOIRE RENAUDIN
- MA country
- France
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
LysaKare 25 g/25 g solution for infusion
PRD7492562 · Product
- Active substance
- Arginine Hydrochloride
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 1 l litre(s)
- Max total dose
- 1 l litre(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- V03AF11 — -
- Marketing authorisation
- EU/1/19/1381/001
- MA holder
- ADVANCED ACCELERATOR APPLICATIONS
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Galliad, 0,74 à 1,85 GBq, générateur radiopharmaceutique
PRD7292120 · Product
- Active substance
- Germanium (68GE) Chloride
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 200 MBq megabecquerel(s)
- Max total dose
- 200 MBq megabecquerel(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- V09X — OTHER DIAGNOSTIC RADIOPHARMACEUTICALS
- Marketing authorisation
- 34009 550 579 0 1
- MA holder
- IRE ELIT
- MA country
- France
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
GalliaPharm 0,74 – 1,85 GBq Radionuklidgenerator
PRD2047327 · Product
- Active substance
- Gallium (68GA) Chloride
- Substance synonyms
- Gallium trichloride (GA68)
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 200 MBq megabecquerel(s)
- Max total dose
- 200 MBq megabecquerel(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- V09X — OTHER DIAGNOSTIC RADIOPHARMACEUTICALS
- Marketing authorisation
- 89872.00.00
- MA holder
- ECKERT & ZIEGLER RADIOPHARMA GMBH
- MA country
- Germany
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
XENETIX 350 (350 mg d’Iode/mL), solution injectable
PRD10944961 · Product
- Active substance
- Iobitridol
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAARTERIAL USE
- Max daily dose
- 150 ml millilitre(s)
- Max total dose
- 150 ml millilitre(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- V08AB11 — IOBITRIDOL
- Marketing authorisation
- 34009 302 822 1 2
- MA holder
- GUERBET
- MA country
- France
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD10864690 · Product
- Active substance
- Loperamide Hydrochloride
- Pharmaceutical form
- CAPSULE
- Route of administration
- ORAL
- Max daily dose
- 16 mg milligram(s)
- Max total dose
- 80 mg milligram(s)
- Max treatment duration
- 5 Day(s)
- Authorisation status
- Authorised
- ATC code
- A07DA03 — LOPERAMIDE
- Marketing authorisation
- 34009 362 197 8 6
- MA holder
- JOHNSON & JOHNSON SANTÉ BEAUTÉ FRANCE
- MA country
- France
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Centre Hospitalier Universitaire De Bordeaux
- Sponsor organisation
- Centre Hospitalier Universitaire De Bordeaux
- Address
- 12 Rue Dubernat, Cs 91286 Cs 91286
- City
- Talence
- Postcode
- 33400
- Country
- France
Scientific contact point
- Organisation
- Centre Hospitalier Universitaire De Bordeaux
- Contact name
- Coordinating Investigator
Public contact point
- Organisation
- Centre Hospitalier Universitaire De Bordeaux
- Contact name
- Coordinating Investigator
Locations
1 EU/EEA country · 5 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| France | Ongoing, recruiting | 23 | 5 |
| Rest of world | — | 0 | — |
Investigational sites
Institut Regional Du Cancer De Montpellier
Médecine nucléaire, 208 Avenue Des Apothicaires, 34298, Montpellier Cedex 5
Centre Hospitalier Universitaire De Bordeaux
Médecine nucléaire, Avenue De Magellan, 33600, Pessac
Centre Hospitalier Universitaire De Nimes
Médecine nucléaire, 4 Place Du Professeur Robert Debre, Bp 40026, Nimes Cedex 9
Institut Bergonie
Médecine nucléaire, 180 R De Saint Genes, 229 Cours De L Argonne, Bordeaux
Oncopole Claudius Regaud
Médecine nucléaire, 1 Avenue Irene Joliot Curie, 31100, Toulouse
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| France | 2021-09-24 | 2021-09-24 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 7 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocole 2024-514785-39-00 public | 8.0 |
| Recruitment arrangements (for publication) | Document not required | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Patient 2024-514785-39-00 | 7.0 |
| Subject information and informed consent form (for publication) | L2_SIS Contraception 2024-514785-39-00 | 1.0 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Lutathera | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Somakit Toc | 1 |
| Synopsis of the protocol (for publication) | D1_Protocole Synopsis FR 2024-514785-39-00 public | 8.0 |
Application history
1 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-10-01 | France | Acceptable 2024-10-21
|
2024-11-04 |