Prove cliniche Nct

Summary
EudraCT Number:2020-002951-39
Sponsor's Protocol Code Number:CAAA601A32201
National Competent Authority:Italy - Italian Medicines Agency
Clinical Trial Type:EEA CTA
Trial Status:Ongoing
Date on which this record was first entered in the EudraCT database:2021-06-04
Trial results
Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL
A. Protocol Information
A.1Member State ConcernedItaly - Italian Medicines Agency
A.2EudraCT number2020-002951-39
A.3Full title of the trial
A multicenter open-label study to evaluate safety and dosimetry of Lutathera in adolescent patients with somatostatin receptor positive gastroenteropancreatic neuroendocrine (GEP-NET) tumors, pheochromocytoma and paragangliomas
Studio in aperto multicentrico per valutare la sicurezza e la dosimetria di Lutathera in pazienti adolescenti con tumori neuroendocrini gastroenteropancreatici (GEP-NET) positivi al recettore della somatostatina, con feocromocitoma e con paragangliomi
A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
Phase 2 study to evaluate safety and dosimetry of Lutathera in adolescent patients with GEP-NETs, pheochromocytoma and paragangliomas
Studio di fase 2 per valutare la sicurezza e la dosimetria di Lutathera in pazienti adolescenti con GEP-NET, feocromocitoma e paragangliomi
A.3.2Name or abbreviated title of the trial where available
NETTER-P
NETTER-P
A.4.1Sponsor's protocol code numberCAAA601A32201
A.7Trial is part of a Paediatric Investigation Plan No
A.8EMA Decision number of Paediatric Investigation Plan
B. Sponsor Information
B.Sponsor: 1
B.1.1Name of SponsorAdvanced Accelerator Applications SA
B.1.3.4CountryFrance
B.3.1 and B.3.2Status of the sponsorCommercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1Name of organisation providing supportAdvanced Accelerator Applications SA
B.4.2CountryFrance
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1Name of organisationAdvanced Accelerator Applications International SA
B.5.2Functional name of contact pointMatthieu Ruffin
B.5.3 Address:
B.5.3.1Street AddressRue de la Tour-de-l'Ile 4
B.5.3.2Town/ cityGeneva
B.5.3.3Post code1204
B.5.3.4CountrySwitzerland
B.5.4Telephone number0041225190700
B.5.5Fax number0033450993071
B.5.6E-mailmatthieu.ruffin@novartis.com
D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation Yes
D.2.1.1.1Trade name Lutathera 370 MBq/mL solution for infusion
D.2.1.1.2Name of the Marketing Authorisation holderAdvanced Accelerator Applications
D.2.1.2Country which granted the Marketing AuthorisationItaly
D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
D.2.5.1Orphan drug designation numberEU/3/07/523
D.3 Description of the IMP
D.3.1Product nameLutathera 370 MBq/mL solution for infusion
D.3.2Product code [Lutathera 370 MBq/mL solution for infusion]
D.3.4Pharmaceutical form Concentrate for solution for infusion
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPIntravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNLUTETIUM (177LU) OXODOTREOTIDE
D.3.9.1CAS number 437608-50-9
D.3.9.2Current sponsor codeLUTETIUM (177LU) OXODOTREOTIDE
D.3.9.4EV Substance CodeSUB180110
D.3.10 Strength
D.3.10.1Concentration unit MBq/ml megabecquerel(s)/millilitre
D.3.10.2Concentration typeequal
D.3.10.3Concentration number370
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin Yes
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
D.3.11.3.2Gene therapy medical product Information not present in EudraCT
D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product Yes
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product No
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.IMP: 2
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation Yes
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.1Product nameLysaKare 25 g/25 g solution for infusion
D.3.2Product code [LysaKare 25 g/25 g solution for infusion]
D.3.4Pharmaceutical form Concentrate for solution for infusion
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPIntravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNL-ARGININA CLORIDRATO
D.3.9.1CAS number 1119-34-2
D.3.9.2Current sponsor codeArginine
D.3.9.4EV Substance CodeSUB22706
D.3.10 Strength
D.3.10.1Concentration unit g/l gram(s)/litre
D.3.10.2Concentration typeequal
D.3.10.3Concentration number25
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNL-LISINA MONOCLORIDRATO
D.3.9.1CAS number 657-27-2
D.3.9.2Current sponsor codeLysine
D.3.9.4EV Substance CodeSUB127503
D.3.10 Strength
D.3.10.1Concentration unit g/l gram(s)/litre
D.3.10.2Concentration typeequal
D.3.10.3Concentration number25
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin Yes
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
D.3.11.3.2Gene therapy medical product Information not present in EudraCT
D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product No
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.8 Information on Placebo
E. General Information on the Trial
E.1 Medical condition or disease under investigation
E.1.1Medical condition(s) being investigated
somatostatin receptor positive gastroenteropancreatic neuroendocrine (GEP-NET) tumors, pheochromocytoma and paragangliomas
Tumori neuroendocrini gastroenteropancreatici (GEP-NET) positivi al recettore della somatostatina, feocromocitoma e paragangliomi
E.1.1.1Medical condition in easily understood language
Tumours that have a specific target (somatostatin receptor)
Tumori che hanno un target specifico (recettore della somatostatina)
E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
MedDRA Classification
E.1.2 Medical condition or disease under investigation
E.1.2Version 21.0
E.1.2Level PT
E.1.2Classification code 10052399
E.1.2Term Neuroendocrine tumour
E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
E.1.2 Medical condition or disease under investigation
E.1.2Version 20.0
E.1.2Level PT
E.1.2Classification code 10077559
E.1.2Term Gastroenteropancreatic neuroendocrine tumour disease
E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
E.1.2 Medical condition or disease under investigation
E.1.2Version 20.0
E.1.2Level LLT
E.1.2Classification code 10077560
E.1.2Term Gastroenteropancreatic neuroendocrine tumor disease
E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
E.1.2 Medical condition or disease under investigation
E.1.2Version 20.1
E.1.2Level LLT
E.1.2Classification code 10034876
E.1.2Term Pheochromocytoma
E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
E.1.2 Medical condition or disease under investigation
E.1.2Version 20.0
E.1.2Level LLT
E.1.2Classification code 10073860
E.1.2Term Paraganglioma
E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
E.1.3Condition being studied is a rare disease Yes
E.2 Objective of the trial
E.2.1Main objective of the trial
- To evaluate organ absorbed radiation doses from PRRT with Lutathera in adolescent patients with SSTR-positive GEP-NETs
- To evaluate safety and tolerability of Lutathera in adolescents with SSTR-positive GEP-NETs
- Per valutare le dosi di radiazioni assorbite dagli organi da PRRT con Lutathera in pazienti adolescenti con GEP-NET SSTR-positivi
- Valutare la sicurezza e la tollerabilità di Lutathera negli adolescenti con GEP-NET SSTR-positivi
E.2.2Secondary objectives of the trial
- To evaluate cumulative safety of Lutathera in adolescents with SSTR-positive GEP-NETs
- To evaluate long-term safety of Lutathera in adolescents with SSTR-positive GEP-NETs
- To perform comparative assessment of dosimetry and pharmacokinetics (PK) between adolescent patients with GEP-NET and adult patients using the extrapolation model developed for the clinical study
- Valutare la sicurezza cumulativa di Lutathera negli adolescenti con GEP-NET SSTR-positivi
- Valutare la sicurezza a lungo termine di Lutathera negli adolescenti con GEP-NET SSTR-positivi
- Eseguire una valutazione comparativa della dosimetria e farmacocinetica (PK) tra pazienti adolescenti con GEP-NET e pazienti adulti utilizzando il modello di estrapolazione sviluppato per lo studio clinico
E.2.3Trial contains a sub-study No
E.3Principal inclusion criteria
1. GEP-NET cohort: Presence of metastasized or locally advanced, inoperable (curative intent), histologically proven, G1 or G2 (Ki-67 index =20%), well differentiated GEP-NET.
PPGL cohort: presence of metastasized or locally advanced, inoperable (curative intent), histologically proven PPGL.
2. Patients from 12 to < 18 years of age at the time of enrollment.
3. Expression of somatostatin receptors confirmed by a somatostatin receptor imaging (SRI) modality within 3 months prior to enrollment, with tumor uptake observed in the target lesions more or equal to the normal liver uptake.
4. Performance status as determined by Karnofsky score = 50 or Lansky Play-Performance Scale score = 50.
1. Coorte GEP-NET: presenza di GEP-NET metastatizzato o localmente avanzato, inoperabile (intento curativo), istologicamente provato, G1 o G2 (indice Ki-67 = 20%), ben differenziato.
Coorte PPGL: presenza di PPGL metastatizzato o localmente avanzato, inoperabile (intento curativo), istologicamente provato.
2. Pazienti di età compresa tra 12 e <18 anni al momento dell'arruolamento.
3. Espressione dei recettori della somatostatina confermata da una modalità di imaging del recettore della somatostatina (SRI) entro 3 mesi prima dell'arruolamento, con assorbimento del tumore osservato nelle lesioni target più o uguale al normale assorbimento epatico.
4. Performance status come determinato dal punteggio Karnofsky = 50 o dal punteggio Lansky Play-Performance Scale = 50.
E.4Principal exclusion criteria
Laboratory parameters:
• Estimated creatinine clearance calculated by the Cockroft-Gault method < 70 mL/min
• Hb concentration <5.0 mmol/L (<8.0 g/dL); WBC <2x109/L; platelets <75x109/L.
• Total bilirubin >3 x ULN for age.
• Serum albumin <3.0 g/dL unless prothrombin time is within the normal range.
Parametri di laboratorio:
• Clearance della creatinina stimata calcolata con il metodo Cockroft-Gault <70 mL / min
• Concentrazione di Hb <5,0 mmol / L (<8,0 g / dL); WBC <2x109 / L; piastrine <75x109 / L.
• Bilirubina totale> 3 x ULN per età.
• Albumina sierica <3,0 g / dL a meno che il tempo di protrombina non rientri nel range normale.
E.5 End points
E.5.1Primary end point(s)
- Target organ (e.g. kidney and bone marrow) absorbed radiation doses in adolescents with SSTR-positive GEP-NETs
- The incidence of adverse events (AEs) and laboratory toxicities after the 1st Lutathera administration in adolescents with SSTR-positive GEP-NETs
- Dosi di radiazioni assorbite da organi bersaglio (ad es. Rene e midollo osseo) negli adolescenti con GEP-NET SSTR-positivi
- L'incidenza di eventi avversi (EA) e tossicità di laboratorio dopo la prima somministrazione di Lutathera negli adolescenti con GEP-NET SSTR-positivi
E.5.1.1Timepoint(s) of evaluation of this end point
After 1st administration
Dopo la prima somministrazione
E.5.2Secondary end point(s)
- The incidence of adverse events (AEs) and laboratory toxicities until 6 months after the last Lutathera dose (short-term follow-up) in adolescents with SSTR-positive GEP-NETs
- The incidence of adverse events (AEs) and laboratory abnormalities during the long term follow-up of 5 years after the last Lutathera dose in adolescents with SSTR-positive GEP-NETs
- Calculated organ absorbed doses and PK parameters based on imaging/blood radioactivity concentration data from adolescent patients with SSTR-positive GEP-NETs compared to the predicted distribution / organ absorbed doses
- L'incidenza di eventi avversi (EA) e tossicità di laboratorio fino a 6 mesi dopo l'ultima dose di Lutathera (follow-up a breve termine) negli adolescenti con GEP-NET SSTR-positivi
- L'incidenza di eventi avversi (EA) e anomalie di laboratorio durante il follow-up a lungo termine di 5 anni dopo l'ultima dose di Lutathera negli adolescenti con GEP-NET SSTR-positivi
- Dosi assorbite dall'organo calcolate e parametri PK sulla base dei dati di imaging / concentrazione di radioattività nel sangue di pazienti adolescenti con GEP-NET SSTR-positivi rispetto alla distribuzione prevista / dosi assorbite dall'organo
E.5.2.1Timepoint(s) of evaluation of this end point
After 1st administration, until 6 months after the last Lutathera dose and until 5 years after the last Lutathera dose
Dopo la prima somministrazione, fino a 6 mesi dopo l'ultima dose di Lutathera e fino a 5 anni dopo l'ultima dose di Lutathera
E.6 and E.7 Scope of the trial
E.6Scope of the trial
E.6.1Diagnosis No
E.6.2Prophylaxis No
E.6.3Therapy No
E.6.4Safety Yes
E.6.5Efficacy No
E.6.6Pharmacokinetic Yes
E.6.7Pharmacodynamic No
E.6.8Bioequivalence No
E.6.9Dose response No
E.6.10Pharmacogenetic No
E.6.11Pharmacogenomic No
E.6.12Pharmacoeconomic No
E.6.13Others Yes
E.6.13.1Other scope of the trial description
Dosimetry
Dosimetria
E.7Trial type and phase
E.7.1Human pharmacology (Phase I) No
E.7.1.1First administration to humans No
E.7.1.2Bioequivalence study No
E.7.1.3Other No
E.7.1.3.1Other trial type description
E.7.2Therapeutic exploratory (Phase II) Yes
E.7.3Therapeutic confirmatory (Phase III) No
E.7.4Therapeutic use (Phase IV) No
E.8 Design of the trial
E.8.1Controlled No
E.8.1.1Randomised No
E.8.1.2Open No
E.8.1.3Single blind No
E.8.1.4Double blind No
E.8.1.5Parallel group No
E.8.1.6Cross over No
E.8.1.7Other Yes
E.8.1.7.1Other trial design description
Aperto
Open
E.8.2 Comparator of controlled trial
E.8.2.1Other medicinal product(s) No
E.8.2.2Placebo No
E.8.2.3Other No
E.8.2.4Number of treatment arms in the trial1
E.8.3 The trial involves single site in the Member State concerned Yes
E.8.4 The trial involves multiple sites in the Member State concerned No
E.8.4.1Number of sites anticipated in Member State concerned1
E.8.5The trial involves multiple Member States Yes
E.8.5.1Number of sites anticipated in the EEA11
E.8.6 Trial involving sites outside the EEA
E.8.6.1Trial being conducted both within and outside the EEA Yes
E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
Canada
United States
Belgium
France
Italy
Netherlands
Poland
Portugal
Spain
Sweden
United Kingdom
E.8.7Trial has a data monitoring committee Yes
E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
The last follow-up visit (5 years after the last dose of Lutathera) will be considered as End of Study (EoS) visit for each patient.
L'ultima visita di follow-up (5 anni dopo l'ultima dose di Lutathera) sarà considerata come visita di fine studio (EoS) per ciascun paziente.
E.8.9 Initial estimate of the duration of the trial
E.8.9.1In the Member State concerned years7
E.8.9.1In the Member State concerned months1
E.8.9.1In the Member State concerned days0
E.8.9.2In all countries concerned by the trial years7
E.8.9.2In all countries concerned by the trial months1
E.8.9.2In all countries concerned by the trial days0
F. Population of Trial Subjects
F.1 Age Range
F.1.1Trial has subjects under 18 Yes
F.1.1.1In Utero No
F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
F.1.1.3Newborns (0-27 days) No
F.1.1.4Infants and toddlers (28 days-23 months) No
F.1.1.5Children (2-11years) No
F.1.1.6Adolescents (12-17 years) Yes
F.1.1.6.1Number of subjects for this age range: 12
F.1.2Adults (18-64 years) No
F.1.3Elderly (>=65 years) No
F.2 Gender
F.2.1Female Yes
F.2.2Male Yes
F.3 Group of trial subjects
F.3.1Healthy volunteers No
F.3.2Patients Yes
F.3.3Specific vulnerable populations Yes
F.3.3.1Women of childbearing potential not using contraception No
F.3.3.2Women of child-bearing potential using contraception Yes
F.3.3.3Pregnant women No
F.3.3.4Nursing women No
F.3.3.5Emergency situation No
F.3.3.6Subjects incapable of giving consent personally No
F.3.3.7Others No
F.4 Planned number of subjects to be included
F.4.1In the member state1
F.4.2 For a multinational trial
F.4.2.1In the EEA 5
F.4.2.2In the whole clinical trial 12
F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
Study Treatment will not be provided to the enrolled patients after completion of the study as Lutathera is administered as 4 doses and this is a full regimen. No provision of Lutathera post-trial is considered necessary.
Il trattamento in studio non sarà fornito ai pazienti arruolati dopo il completamento dello studio poiché Lutathera viene somministrato in 4 dosi e questo è un regime completo. Nessuna disposizione di Lutathera dopo il processo è considerata necessaria.
G. Investigator Networks to be involved in the Trial
N. Review by the Competent Authority or Ethics Committee in the country concerned
N.Competent Authority Decision Authorised
N.Date of Competent Authority Decision2021-04-07
N.Ethics Committee Opinion of the trial applicationFavourable
N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
N.Date of Ethics Committee Opinion2021-02-24
P. End of Trial
P.End of Trial StatusOngoing

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