E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
children with recurrent or refractory medulloblastoma and newly diagnosed high-grade glioma |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10061030 |
E.1.2 | Term | Brain tumour |
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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 assess the rate of objective confirmed tumor response of irinotecan in combination with temozolomide in children with recurrent or refractory medulloblastoma and in children with newly diagnosed high-grade glioma.
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E.2.2 | Secondary objectives of the trial |
• To determine the duration of tumor response, time to tumor progression (TTP), time to treatment failure (TTF), and overall survival (OS)
• To assess the safety and tolerability of the combination of irinotecan and temozolomide
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
CLINICAL PHARMACOGENOMICS SUPPLEMENT. PHASE 2 SINGLE-ARM, OPEN LABEL STUDY OF IRINOTECAN IN COMBINATION WITH TEMOZOLOMIDE IN CHILDREN WITH RECURRENT OR REFRACTORY MEDULLOBLASTOMA AND IN CHILDREN WITH NEWLY DIAGNOSED HIGH-GRADE GLIOMA (October 6th, 2006 - Final) The objective of this additional research component is to allow for the collection, storage, and use of samples to investigate possible associations between genomic variation in O6-methylguanine-DNA-methyltransferase (MGMT) and microsatellite instability (MSI), among others, in relation to response to the combination of irinotecan and temozolomide and in relation to characteristics of refractory or recurrent medulloblastoma and newly diagnosed high-grade glioma and related conditions. |
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E.3 | Principal inclusion criteria |
1. Histologically or cytologically confirmed tumors 2. Cohort 1: Recurrent or refractory medulloblastoma in which current standard treatment approaches have failed; biopsy is not required for recurrent disease.
Cohort 2: Newly-diagnosed high-grade glioma (WHO grade 3 or 4) 3. Measurable primary and/or metastatic disease: at least one bi-dimensionally measurable lesion on MRI 4. No previous treatment with temozolomide or irinotecan 5. Age at inclusion: 6 months to ≤ 18 years 6. Lansky-Play scale ≥ 70% or ECOG performance status ≤ 1 as appropriate based on age 7. Life expectancy ≥ 3 months 8. Adequate organ function: Hematological function: neutrophil count ≥ 1 x 109/L, platelet count ≥ 100 x 109/L, hemoglobin ≥ 8 g/dL. Renal function: creatinine ≤ 1.5 x ULN for age. If serum creatinine is > 1.5 ULN of age, then creatinine clearance (or radioisotope GFR) must be > 70 mL/min/1.73 m². Hepatic function: bilirubin ≤ 1.5 x ULN; AST and ALT ≤ 2.5 x ULN 9. For medulloblastoma: wash out period of 3 weeks in case of prior chemotherapy, 6 weeks if treatment included nitrosoureas; 6 weeks in case of prior radiotherapy. Subjects must have recovered from the acute toxic effects of all prior therapy before enrollment into the study 10. Able to comply with scheduled follow-up and with management of toxicity 11. All subjects with reproductive potential must practice an effective method of birth control while on study. Female subjects with childbearing potential must have a negative pregnancy test within 8 days before study treatment 12. Written informed consent from subject, parent(s) or legal guardian(s) provided prior to enrollment in this study
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E.4 | Principal exclusion criteria |
1. Diagnosis of brainstem glioma 2. Concurrent administration of any other anti-tumor therapy 3. Pre-existing uncontrolled diarrhea 4. Pregnant or breast feeding 5. Current participation in another clinical trial 6. A serious concomitant systemic disorder (for example, active infection including HIV or cardiac disease) that in the opinion of the investigator, would compromise the subject’s ability to complete the study 7. Subjects with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is defined as the proportion of subjects who had a documented complete or partial tumor response (occurring within the first 2 or 4 cycles of treatment for glioma and medulloblastoma, respectively) which must be confirmed by a follow-up objective tumor response assessment obtained ≥ 4 weeks after the initial documentation. |
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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 | No |
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 | Yes |
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 | 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) | 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 | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 60 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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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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End of trial in all participating countries is defined as the date of the last follow-up visit. The overall survival is an endpoint. |
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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 | 18 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 30 |