E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diffuse pontine glioma in children |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10006143 |
E.1.2 | Term | Brain stem glioma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
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 evaluate the time to death in patients with newly diagnosed diffuse pontine gliomas, when treated with the combination of concomitant low dose oral Temozolomide and radiation therapy, followed by up to 12 months maintenance therapy with extended low dose Temozolomide. • To assess the quality of life in patients with diffuse pontine gliomas during and after the above treatment. |
|
E.2.2 | Secondary objectives of the trial |
• To evaluate the time to tumour progression in patients with newly diagnosed diffuse pontine gliomas. • To evaluate and document toxicities from study treatment. • To document radiological response to treatment with an MRI scan (measures the size of the tumour) and where available through functional imaging (assesses the activity of the tumour rather than size alone) |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
a) Newly diagnosed diffuse intrinsic lesion centred in the pons on MRI imaging. No requirement for histological diagnosis. Clinical history of < 6 months. Clinical findings must include at least one of the 3 following signs of brainstem tumour i) cranial nerve deficit ii) long tract signs iii) ataxia b) Age between 2 and 21 years at initial diagnosis (i.e. up to but not including 22nd birthday) c) Patient has a Karnofsky Performance Status (KPS) or a Lansky play score of greater than or equal to 60 unless reason for decrease in status is a direct result of neurological involvement of the brainstem glioma (Appendix B). d) Patient’s laboratory values (performed within 14 days prior to study drug administration, inclusive) are as follows: i) Absolute neutrophil count (ANC) greater than or equal to 1.0 x 109/L ii) Platelet count greater than or equal to 100 x 109/L iii) Haemoglobin greater than or equal to 10 g/dL iv) Urea and serum creatinine <1.5 times upper limit of laboratory normal. v) Total and direct bilirubin <1.5 times upper limit of laboratory normal. vi) Serum AST and ALT <3 times upper limit of laboratory normal. e) Patient has life expectancy of greater than 12 weeks. f) A negative pregnancy test within 7 days prior to administration of Temozolomide for women of childbearing potential, and sexually active patients and partners agreeing to undertake adequate contraceptive measures g) Parent (and patient if appropriate) has given written informed consent. h) National and local ethical approval and regulatory approval. |
|
E.4 | Principal exclusion criteria |
a) Focal lesions of brainstem. b) Predominantly exophytic tumours. c) Patient has received prior chemotherapy or radiotherapy. d) Patient has frequent vomiting and/or medical condition, which could interfere with oral medication intake (e.g. partial bowel obstruction). e) Pregnant or breastfeeding women. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
• Median survival times to tumour progression and to death after study entry. The response rate will be summarised and compared to historical controls treated with standard radiotherapy alone. • Quality of Life assessments will measure health status, behaviour and the subjective experience using HUI and SDQ methods. • Evaluation of toxicity, steroid usage, radiological response will be undertaken. • Adverse events including abnormal laboratory parameters will be tabulated and changes from baseline using CTC criteria will be summarized |
|
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 | 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 | 21 |
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 | 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
|
At maximum 12 months from start of temozolomide maintenance administration providing there is no tumour progression. Patients will then be followed up for survival until death. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |