E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
pediatric patients with HGG/DIPG |
pazienti pediatrici affetti da gliomi ad alto grado o tumori intrinseci diffusi del ponte |
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E.1.1.1 | Medical condition in easily understood language |
pediatric patients (aged between 5 and 18 years) with HGG/DIPG |
pazienti pediatrici (età compresa tra i 5 e i 18 anni) affetti da glioma ad alto grado o tumori diffusi intrinseci del ponte |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10029104 |
E.1.2 | Term | Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Evaluate the diagnostic accuracy of 64CuCl2-PET / CT in identifying HGG and DIPG Correlate the intensity of 64CuCl2 with tumor aggressiveness Evaluate the prognostic impact of 64CuCl2 (i.e. the ability to identify patients at increased risk of disease progression) |
Valutare l’accuratezza diagnostica della 64CuCl2- PET/CT nell’identificare gli HGG e i DIPG; Correlare l’intensità del 64CuCl2 con l’aggressività tumorale; Valutare l’impatto prognostico del 64CuCl2 (i.e. la capacità di identificare i pazienti a maggior rischio di progressione di malattia) |
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E.2.2 | Secondary objectives of the trial |
To study biodistribution, kinetics and dosimetry based on MIRD method of 64CuCl2 both in the tumor lesion and in the organs Evaluating the Tumor to Background ratio (TBR) of 64CuCl2 in function of time Evaluate the safety and tolerance of 64CuCl2 and possible occurrence of adverse events |
Studiare la biodistribuzione, la cinetica e la dosimetria basata sul metodo MIRD del 64CuCl2 sia nella lesione tumorale sia negli organi; Valutare l’andamento temporale del Tumour to Background ratio (TBR) del 64CuCl2; Valutare la sicurezza e la tolleranza del 64CuCl2 e l’eventuale insorgenza di eventi avversi |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Histologically or radiologically confirmed High grade Glioma or diffuse intrinsic pontine glioma (DIPG)
2. Measurable disease (at least one objectively bi-dimensionally measurable lesion (> 1 cm in its largest dimension by RM scan) as demonstrated by RM scan.
3.KPS = 60.
4. A life expectancy > 3 months.
5. Male or female aged ranging from 5 to 18 years. 6. Normal marrow function defined as: a. Absolute neutrophil count = 1.5 x 109/l b. Platelet count = 150 x 109/l c. Haemoglobin = 9 g/dl. 7. Adequate hepatic function, defined as: a. AST/ALT = 2.5 x upper limit of normal (ULN) (or = 5.0 x ULN if liver involvement by primary disease) direct bilirubin = 1.5 ULN b. Normal ALP values c. Normal coagulation parameters. 8. Adequate renal function as demonstrated by a serum creatinine = 1.5 mg/dl or a creatinine clearance > 60 ml/min. 9. Negative human chorionic gonadotropin (hCG) test in women of childbearing potential. Sexually active male and female patients of childbearing potential must agree to use an effective method of birth control (e.g. barrier methods with spermicides, oral or parenteral contraceptives and/or intrauterine devices) during the entire duration of the study and for 4 months after final administration of 64CuCl2, or the patient must be sterile (with documentation in the patient’s medical records). Note: Sterility (in female patients) must be confirmed in the patients’ medical records and can be defined as any of the following: surgical hysterectomy with bilateral oophorectomy; radiation-induced oophorectomy with last menses >1 year ago; chemotherapy-induced menopause with 1 year interval since last menses. 10. Written, informed consent prior to the present study and to any study-specific screening procedures, with the understanding that the consent may be withdrawn by the patient or by the parents/legal tutors at any time without prejudice. 11. Capable of understanding the protocol requirements, is willing and able to comply with the study protocol procedures, and has signed the informed consent document.
15.TBR > 5 |
1. HGG/DIPG istologicamente o radiologicamente confermati; 2. Malattia misurabile (almeno una lesione oggettivamente misurabile bi-dimensionalmente >1.0 cm nel suo diametro massimo) con RM; 3. KPS = 60; 4. Aspettativa di vita maggiore di 3 mesi; 5. Maschio o Femmina collaborativi di età compresa tra i 5 e i 18 anni; 6. Funzione midollare normale definita come: a. Conteggio assoluto neutrofili = 1.5x109/L b. Conteggio piastrine = 150x109/L c. Emoglobina = 9 g/L 7. Funzione epatica adeguata, definita come: a. AST/ALT = 2.5 x limite superiore di normalità (ULN) (o = 5.0 x ULN se presenti localizzazioni epatiche di malattia) bilirubina diretta = 1.5 ULN; funzione renale adeguata con creatinina sierica = 1.5 mg/dl o clearance della creatinina > 60 ml/min b. Valori normali di ALP c. Parametri di coagulazione normali 8. Funzione renale adeguata con creatinina sierica = 1.5 mg/dl o clearance della creatinina > 60 ml/min; 9. Gonadotropina corionica umana negativa (hCG) nelle ragazze potenzialmente in gravidanza. I pazienti di entrambi i sessi con attività sessuale attiva useranno metodi a scopo anticoncezionale (e.s. metodi barriera con spermicidi, contraccettivi orali o parenterali e/o dispositivi intrauterini) durante ‘intera durata dello studio e per i 6 mesi successivi al termine della somministrazione finale di 64CuCl2. Nota: la sterilità (nelle pazienti di sesso femminile) deve essere confermata nelle cartelle mediche e può essere definita con le seguenti: istero-annessiectomia bilaterale chirurgica, ovariectomia radio-indotta con ultime mestruazioni > 1 anno; menopausa indotta da chemioterapia con un intervallo di 1 anno dalle ultime mestruazioni; 10. Consenso informato scritto precedente ad ogni procedura specifica dello studio. Procedure di screening, con la conoscenza che il consenso potrebbe essere ritirato dal paziente o dai parenti/tutori legali in qualsiasi momento senza pregiudizio; 11. Capacità di comprendere le richieste del protocollo e abilita di rispettare le procedure del protocollo di studio. |
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E.4 | Principal exclusion criteria |
1. Histology other than High Grade Glioma. 2. Contraindication to MRI with gadolinium. 3. Copper metabolic disorders (i.e. known Wilson disease or Menkes disease). 4. Patients who have not recovered from adverse events Grade > 1 due to diagnostic injection of Cuprymina. 5. Pregnant or breastfeeding women. 6.Sexually active male and female patients of childbearing potential without use of an effective method of birth control. 7.Known HIV disease or acquired immunodeficiency syndrome-related illness or active hepatitis B or C infection. 8. Uncontrolled Diabetes |
1. Istologia e/o imaging RM non compatibile con HGG/DIPG; 2. Controindicazioni alla RM con gadolinio; 3. Disordini metabolici del rame (e.s. diagnosi di malattia di Wilson o di Menkes); 4. Pazienti con malattia intercorrente non controllata: infezione attiva o in corso, insufficienza cardiaca congestizia sintomatica, angina pectoris instabile, aritmia cardiaca o malattie psichiatriche/situazioni sociali che limiterebbero la conformità ai requisiti dello studio; 5. Donne in gravidanza o in allattamento; 6. Pazienti di entrambi i sessi sessualmente attivi che non utilizzano dispositivi anticoncezionali; 7. Pazienti HIV positivi o con sindrome da immunodeficienza acquisita o epatite B o C attiva; 8. Diabete non controllato. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Evaluate the diagnostic accuracy of 64CuCl2-PET / CT in identifying HGG and DIPG Correlate the intensity of 64CuCl2 with tumor aggressiveness Evaluate the prognostic impact of 64CuCl2 (i.e. the ability to identify patients at increased risk of disease progression) |
Valutare l’accuratezza diagnostica della 64CuCl2- PET/CT nell’identificare gli HGG e i DIPG; Correlare l’intensità del 64CuCl2 con l’aggressività tumorale; Valutare l’impatto prognostico del 64CuCl2 (i.e. la capacità di identificare i pazienti a maggior rischio di progressione di malattia) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
To study biodistribution, kinetics and dosimetry based on MIRD method of 64CuCl2 both in the tumor lesion and in the organs Evaluating the Tumor to Background ratio (TBR) of 64CuCl2 in function of time Evaluate the safety and tolerance of 64CuCl2 and possible occurrence of adverse events |
Studiare la biodistribuzione, la cinetica e la dosimetria basata sul metodo MIRD del 64CuCl2 sia nella lesione tumorale sia negli organi; Valutare l’andamento temporale del Tumour to Background ratio (TBR) del 64CuCl2; Valutare la sicurezza e la tolleranza del 64CuCl2 e l’eventuale insorgenza di eventi avversi |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
to assess whether 64CuCI2 could eventually influence patient management |
impatto clinico eventuale |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
studio pilota di efficacia diagnostica nello stesso gurppo di pazienti |
pilot study of diagnostic accuracy |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial 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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |