E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Neuroblastoma that hasn't responded to standard treatment or that has relapsed. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
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 |
The trial will evaluate how effective 177Lutetium DOTATATE is in children with high-risk relapsed or refractory neuroblastoma and determine the safety and adverse events of the treatment experienced by patients on the study. |
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E.2.2 | Secondary objectives of the trial |
The trial aims to determine whether there is a relationship between the absorbed dose to the tumour and response to 177Lutetium DOTATATE. To correlate the somatostatin receptor sub-type 2 expression in the original histology specimens from primary surgery with 68Gallium DOTATATE PET/CT uptake (SUVmax values) To correlate the uptake on 68Gallium DOTATATE PET/CT by SUVmax scores with response to 177Lutetium DOTATATE therapy. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Histologically confirmed diagnosis of neuroblastoma - Relapsed or primary refractory high risk neuroblastoma (International Neuroblastoma Staging System stage 4 or International Neuroblastoma Risk Group staging System M) - Age >18 months and <18 years of age at the time of enrolment into the study - Life expectancy of greater than 3 months - Performance Status: Karnofsky 50% or more (for patients >12 years of age) Lansky 50% or more (for patients <12 years of age) - Adequate recovery from major surgery prior to receiving study treatment - Uptake in primary tumour or metastatic tumour deposits on 68Gallium DOTATATE PET/CT at least as high as the liver uptake and performed within a month prior to trial - I-MIBG and FDG PET/CT within a month prior to trial entry - Two week washout from any prior treatment - Patients must have recovery of hematological toxicity following previous therapy - Laboratory requirements within 7 days of commencement of therapy • Haemoglobin, If Hb is <12g/dl then patient will receive a blood transfusion prior to treatment • Absolute neutrophil count > 1.0 x 10^9/L • Absolute Platelets > 100 x 10^9/L Biochemistry: • Bilirubin within normal range • ALT within 2.5 x ULN • ALP within 5 x ULN - Glomerular Filtration rate >50mL/min/1.73m2 - Before patient registration, written informed consent. - Parents or other appropriate adult to sign the local Comforters and Carers consent before patient registration. - Agreed to a follow up of 5 years. |
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E.4 | Principal exclusion criteria |
- Not fit enough to undergo proposed study treatment - Concurrent treatment with any anti-tumour agents - Prior treatment with other radiolabelled somatostatin analogues - 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
Response rate by International Neuroblastoma Response Criteria at one month after the completion of therapy. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Evaluated at 1 month, 4 months, and then every 6 months until progression |
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E.5.2 | Secondary end point(s) |
ToxicityProgression free survival Overall survival Response rate by International Neuroblastoma Response criteria at four months after completion of therapy. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Toxic effects - To be evaluated during treatment at 1 month and 4 months post therapy or until all treatment related events have resolved. Progression free survival - at point of relapse Overall survival - up to 5 years of completion of therapy. |
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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 | Yes |
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 | 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 | 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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
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 | 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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The trial end date is deemed to be 6 months after the last patient has completed study treatment. |
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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 | 2 |
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 | 0 |
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 |