E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Neuroblastoma and Other pediatric solid tumours. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066595 |
E.1.2 | Term | Neuroblastoma recurrent |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the response rate of Temozolomide in combination with Topotecan in patients with relapsed or refractory neuroblastoma, and to describe response in patients with relapsed or refractory brain tumours other than medulloblastoma and in patients with relapsed or refractory other solid tumours |
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E.2.2 | Secondary objectives of the trial |
- To determine duration of response, time to progressive disease, time to treatment failure and overall survival - To assess adverse events and toxicity profile of the combination. - To evaluate MGMT expression on archive tumour material by multiple technical modalities : MS-HRM, COBRA, HPLC and pyrosequencing and correlate with response
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Histologically or cytologically confirmed neuroblastoma, medulloblastoma, CNS tumor, or other non-CNS solid tumor (at diagnosis) -Relapsed or refractory tumours in which correct standard treatment approaches have failed -No more than 2 lines of prior chemotherapy -Measurable primary and/or metastatic disease on CT/MRI: at least one bi-dimensionally measurable lesion -Age at inclusion: 6 months to ≤ 20 years -Lansky play score ³ 70% or ECOG performance status ≤ 1- Life expectancy ³ 3 months- Adequate organ function:Adequate hematological function: hemoglobin ³ 80 g/L, neutrophil count ³ 1.0 x 109/L, platelet count ³ 100 x 109/L; in case of bone marrow disease: neutrophils ³ 0.5 x 109/L and platelets ≥ 75 x 109/L; Adequate renal function: normal creatinine related to patient’s age: 0 – 1 year: ≤ 40 µmol/L1 – 15 years: ≤ 65 µmol/L 15 – 20 years: ≤ 110 µmol/L Adequate hepatic function: bilirubin £ 1.5 x ULN; AST and ALT £ 2.5 x ULN (AST, ALT ≤ 5 x ULN in case of liver metastases) -Wash out of 4 weeks in case of prior chemotherapy, 6 weeks if treatment included nitrosoureas, 2 weeks in case of vincristine alone; 6 weeks in case of prior radiotherapy (except palliative radiotherapy on non measurable lesions). Patients must have recovered from the acute toxic effects of all prior therapy before enrollment into the study -Patients previously treated with only one of the 2 drugs are eligible -Able to comply with scheduled follow-up and with management of toxicity -All patients with reproductive potential must practice an effective method of birth control while on study. Female patients aged > 12 years must have a negative pregnancy test within 7 days before study treatment -Written informed consent from patient, parents or legal guardian
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E.4 | Principal exclusion criteria |
-Concurrent administration of any other antitumor therapy -Serious concomitant systemic disorder (for example, active infection including HIV or cardiac disease) that in the opinion of the investigator, would compromise the patient’s ability to complete the study -History of allergic reaction to the compounds or their solvents -History of allergic reaction to Dacarbazin (DITC) -Galactosemia, Glucose-galactose malabsorption or lactase deficiency -Pregnant or breast feeding young women -Presence of symptomatic brain metastases in patients with solid non-CNS tumors
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the percentage of patients achieving complete or partial response, after having received 2 cycles of Temozolomide - Topotecan (8 weeks) |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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 | No |
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 | |
E.8.9.1 | In the Member State concerned months | 30 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 30 |