E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary refractory or relapsed high-risk neuroblastoma.
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Pirminė gydymui atspari ar recidyvavusi didelės rizikos neuroblastoma. |
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E.1.1.1 | Medical condition in easily understood language |
Primary refractory or relapsed high-risk neuroblastoma. |
Pirminė gydymui atspari ar recidyvavusi didelės rizikos neuroblastoma. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029260 |
E.1.2 | Term | Neuroblastoma |
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 |
To confirm the dose and assess response to single agent 177Lutetium-DOTATATE treatment in patients with relapsed or refractory high-risk neuroblastoma. |
Patvirtinti dozę ir įvertinti atsaką į vieną vaistą 177Letecio-DOTATATE, skiriamą pacientams, kuriems yra recidyvuojanti ar refrakterinė didelės rizikos neuroblastoma. |
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E.2.2 | Secondary objectives of the trial |
To assess long term survival and response - To assess treatment-related toxicity - To correlate tumour dosimetry with response - To correlate somatostatin type 2 receptor (SSTR-2) expression with 68Ga-DOTATOC PET/CT uptake - To correlate the uptake on 68Ga-DOTATOC PET/CT with response to 177Lu-DOTATATE therapy |
Įvertinti ilgalaikį išgyvenamumą ir atsaką - Įvertinti su gydymu susijusį toksiškumą - Susieti naviko gydymui skiriamą dozimetriją su atsaku į gydymą - koreliuoti 2 tipo somatostatino receptoriaus (SSTR-2) išraišką su 68Ga-DOTATOC PET / CT įsisavinimu - Koreguoti 68Ga-DOTATOC PET / CT pasisavinimą su atsaku į 177Lu-DOTATATE terapiją |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Pathology 1.1. Histologically confirmed diagnosis of neuroblastoma 1.2. Immunohistochemical staining for somatostatin receptors (SSTR) performed from primary tumor tissue when available
2. Relapsed or primary refractory high-risk neuroblastoma: INSS stage 4 disease or INRGSS stage M disease
3. Age >18 months and < 18 years of age at the time of enrolment into this study
4. Life expectancy of greater than 3 months
5. Performance Status 5.1. Karnofsky > 50% (for patients > 12 years of age) 5.2. Lansky > 50% (for patients ≤ 12 years of age)
6. Prior treatment 6.1. Two-week washout from any prior treatment 6.2. Patients must have recovery of hematological toxicity following previous therapy 6.3. Adequate recovery from major surgery prior to receiving study treatment
7. Diagnostic imaging 7.1. Uptake in the primary tumor or metastatic tumour deposits on 68Ga-DOTATATE PET/CT at least higher than the liver uptake and performed within two months prior to registration 7.2. 123I-mIBG scintigraphy to be performed within two months prior to registration 7.3. CT or MRI of the primary tumor and bulky metastatic sites within two months prior to registration
8. Laboratory requirements to be performed within 7 days prior to commencing trial treatment: 8.1. Hematology: 8.1.1. Hemoglobin, If Hb is <120 g/L then patient will receive a blood transfusion prior to commencing trial treatment 8.1.2. Absolute neutrophil count > 1.0 x 109/L 8.1.3. Absolute Platelets > 100 x 109/L 8.2. Biochemistry: 8.2.1. Bilirubin within 1.5 x ULN 8.2.2. ALT within 2.5 x ULN 8.2.3. ALP within 5 x ULN 8.2.4. Glomerular filtration rate >50mL/min/1.73m2 assessed using Iohexol clearance or creatinine clearance and performed within 2 months prior to registration 8.2.5. Urinary catecholamine metabolites measured within 2 months prior to registration
9. Peripheral blood stem cells (PBSC) 9.1. A minimum of 4 x106 CD34+ cells/kg (optimally 6 x106 CD34+ cells/kg) must be available for each study subject prior to registering
10. Parents or appointed legal guardian to sign the written informed consent prior to registration or any trial-related screening procedures |
1. Patologija 1.1. Histologiškai patvirtinta neuroblastomos diagnozė 1.2. Imunohistocheminis somatostatino receptorių dažymas, atliekamas iš pirminio naviko audinio, jeigu taikoma
2. Atsinaujinusi arba pirminė refrakterinė didelės rizikos neuroblastoma: INSS 4 stadijos liga arba INRGSS M stadijos liga
3. Amžius> 18 mėnesių ir <18 metų dalyvaujant šiame tyrime
4. Gyvenimo trukmė ilgesnė nei 3 mėnesiai
5. Veiklos būsena 5.1. Karnofsky> 50% (pacientams> 12 metų) 5.2. Lansky> 50% (pacientams iki 12 metų)
6. Išankstinis gydymas 6.1. Dviejų savaičių plovimas nuo bet kokio ankstesnio gydymo 6.2. Po ankstesnio gydymo pacientams turi atsistatyti hematologinis toksiškumas. 6.3. Tinkamas atsigavimas po didelės operacijos prieš pradedant gydymą tiriamuoju
7. Diagnostinis vaizdavimas 7.1. Pirminio naviko arba metastazavusio naviko pasisavinimas ant 68Ga-DOTATATE PET / CT bent jau didesnis nei kepenų pasisavinimas ir atliktas per du mėnesius iki registracijos 7.2. 123I-mIBG scintigrafija turi būti atlikta per du mėnesius iki registracijos 7.3. Pirminio naviko ir didelių metastazių vietų KT ar MRT per du mėnesius iki registracijos
8. Laboratorijos reikalavimai, kurie turi būti įvykdyti per 7 dienas prieš pradedant bandomąjį gydymą: 8.1. Hematologija: 8.1.1. Hemoglobinas, jei Hb yra <120 g / l, prieš pradedant gydymą pacientui bus perpiltas kraujas 8.1.2. Absoliutus neutrofilų skaičius> 1,0 x 109 / L 8.1.3. Absoliutiosios trombocitai> 100 x 109 / L 8.2. Biochemija: 8.2.1. Bilirubinas neviršija 1,5 x ULN 8.2.2. ALT 2,5 x ULN ribose 8.2.3. ALP 5 x ULN ribose 8.2.4. Glomerulų filtracijos greitis> 50mL / min / 1,73m2 įvertintas naudojant ioheksolio klirensą arba kreatinino klirensą ir atliktas per 2 mėnesius iki registracijos 8.2.5. Šlapimo katecholamino metabolitai išmatuoti per 2 mėnesius iki registracijos
9. Periferinio kraujo kamieninės ląstelės (PBSC) 9.1. Kiekvienam tiriamajam prieš registruojantis turi būti mažiausiai 4 x 106 CD34 + ląstelės / kg (optimaliai - 6 x 106 CD34 + ląstelės / kg).
10. Tėvai ar paskirtas teisėtas globėjas pasirašo rašytinį informuotą sutikimą prieš registruodamiesi ar atlikdami bet kokią su bandymu susijusią patikrinimo procedūrą
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E.4 | Principal exclusion criteria |
1. Not fit enough to undergo proposed study treatment, as assessed by national PI
2. Pregnant or lactating patient
3. Concurrent treatment with any anti-tumor agents
4. Prior treatment with other radiolabeled somatostatin analogues
5. Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient or legal guardian before registration in the trial
6. Hypersensitivity to any component of the investigational drug Lutathera® |
1. Nepakankamas, kad būtų atliktas siūlomas tyrimo gydymas, kaip įvertino pagrindinis tyrėjas
2. Besilaukianti arba maitinanti pacientė
3. Kartu vartojami priešnavikiniai vaistai
4. Ankstesnis gydymas kitais radioaktyviai žymėtais somatostatino analogais
5. Bet kokia psichologinė, šeimos, sociologinė ar geografinė būklė, galinti trukdyti laikytis tyrimo protokolo ir tolesnio plano
6. Padidėjęs jautrumas bet kuriam tiriamojo vaisto „Lutathera®“ komponentui |
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E.5 End points |
E.5.1 | Primary end point(s) |
Response by the Revised International Neuroblastoma Response Criteria (INRC). |
Atsakymas pagal patikslintus tarptautinius neuroblastomos atsako kriterijus. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At 1 month after the completion of therapy. |
Praėjus 1 mėnesiui po gydymo pabaigos. |
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E.5.2 | Secondary end point(s) |
1 Response by the Revised INRC criteria 2 Progression free survival (PFS) 3 Overall survival (OS) 4 Hematological and renal toxicity according to CTCAE 5.0 |
1 Atsakymas pagal tarptautinius neuroblastomos atsako kriterijus 2 Išgyvenamumas be progresavimo 3 Bendras išgyvenamumas 4 Hematologinis ir inkstų toksiškumo vertinimas |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1 At 4 months after the completion of therapy. 2 From registration until objective tumour progression or death or to date of censoring for patients who do not experience the event during trial follow-up. 3 From registration into the trial until date of death from any cause or to date of censoring for patients who do not experience the event during trial follow-up. 4 From registration until the 4 months' follow-up. |
1 Praėjus 4 mėnesiams po gydymo pabaigos. 2 Nuo registracijos iki objektyvaus naviko progresavimo ar mirties 3 Nuo registracijos iki tyrimo iki mirties dėl bet kokios priežasties dienos 4 Nuo registracijos iki 4 mėnesių tolesnių veiksmų. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
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 | No |
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 | Yes |
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 | No |
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.8.3 |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
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 | No |
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 | 6 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |