Radiochemotherapy trial with radiotherapy and temozolomide chemotherapy for children and young adolescents 3 years and older to 18 years of age with primary high grade glioma, pontine glioma or gliomatosis cerebri
| ISRCTN | ISRCTN19852453 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN19852453 |
| EudraCT/CTIS number | 2007-000128-42 |
| Secondary identifying numbers | EudraCT 2007-000128-42; BfArM 4034262 |
- Submission date
- 25/05/2009
- Registration date
- 05/06/2009
- Last edited
- 01/07/2016
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year
Plain English summary of protocol
Not provided at time of registration
Contact information
Dr Christof Kramm
Scientific
Scientific
University Children's Hospital
Ernst-Grube-Str.40
Halle
06120
Germany
| christoph.kramm@medizin.uni-halle.de |
Study information
| Study design | Multinational prospective non-randomised phase II trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | International cooperative phase II trials of the HIT-HGG study group for the treatment of high grade glioma, diffuse intrinsic pontine glioma, and gliomatosis cerebri in children and adolescents 3 years and older up to 18 years |
| Study acronym | HIT-HGG-2007 |
| Study objectives | Based on the experience of the Adult Glioblastoma EORTC trial with oral temozolomide and radiotherapy, a phase II trial with oral temozolomide in parallel to radiotherapy and as subsequent consolidation treatment will be performed. This will be investigated if the resulting 6-month event-free-survival (EFS) will support the initiation of a phase III trial in which long term EFS and the randomised evaluation of the therapeutic efficiency of an immune therapeutic approach in parallel to oral temozolomide consolidation chemotherapy will be successful. Main general objectives: 1. Is a simultaneous radiochemotherapy with radiotherapy and a 5 - 6 weeks course of oral temozolomide at 75 mg/m^2/d followed by additional 12 cycles of oral temozolomide given as a 5 day course at 150 - 200 mg/m^2/d every 28 days efficacious? 2. EFS and treatment related toxicities for each treatment element will be evaluated in comparison to the results of the previous paediatric HIT-GBM-C and -D trials for treatment of primary high grade glioma, diffuse intrinsic pontine glioma, and gliomatosis cerebri Primary objectives: 1. Is treatment with temozolomide efficacious? Treatment is considered to be efficacious if the probability for "no event within the first 6 months after diagnosis" is not inferior in comparison with the corresponding 6-months EFS rates of the HIT-GBM-C and D cohort. That means that the probability for "no event within the first 6 months after diagnosis" is not less than or equal to 46% for patients with a pontine tumour and not less than or equal to 53% for patients with a non-pontine tumour. The probability for being event-free 6 months after diagnosis is different for patients with and without a pontine tumour. Secondary objectives: 1. Do the overall survival (OS) and event-free survival (EFS) of patients of the HIT-HGG-2007 trial differ from the OS/EFS of patients of the historical control groups (HIT-GBM-C and -D)? 2. Does the HIT-HGG-2007 treatment leads to different toxicity rates in comparison to the historical control group (HIT-GBM-C and -D)? 3. Has the methylation of the O6-MGMT (O6-methylguanine-DNA methyltransferase) gene promoter within the primary tumour an influence on the EFS? (similar to reports in adult patients with glioblastoma) 4. Do the following clinical parameters have an influence on EFS or OS? 4.1. Tumour location (ICD-O classification) 4.2. Tumour grading 4.3. Centrally reviewed histology (World Health Organization [WHO] classification) 4.4. Extent of tumour resection (as defined by early post surgical imaging, preferentially magnetic resonance imaging) 4.5. Genetic syndromes 4.6. Secondary malignancies 4.7. Age at diagnosis 4.8. Gender 4.9. Relapse treatment 5. Is there an association between these clinical parameters and the affiliation to one of the two patient groups HIT-HGG-2007 and HIT-GBM-C/-D? Tertiary objectives: 1. Neuropsychological testing and evaluation of the quality of life during different time points in the course of disease and treatment. By establishing this testing program future treatment modalities can be directly compared in regards to neuropsychological outcome and resulting quality of life. 2. Establishment of routine sterile fresh frozen tumour sampling and mailing on dry ice to the tumour tissue bank of the HIT network at the Institute of Neuropathology, Bonn, Germany. Is there an increase of the current tumour bank entry rate which was approximately 15 % of all possible cases within HIT-GBM-D? 3. Establishment of routine investigation of tumour paraffin material for potential therapeutic targets for individualised relapse treatment. These targets include: epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor alpha (PDGFR alpha), c-kit, PTEN, vascular endothelial growth factor receptor (VEGFR) 1,2. Investigations will be performed during central neuropathological review. |
| Ethics approval(s) | Ethics Board of the Medical Faculty of the Martin Luther University of Halle-Wittenberg approved on the 19th March 2009 |
| Health condition(s) or problem(s) studied | Primary high grade glioma, pontine glioma or gliomatosis cerebri |
| Intervention | 1. Surgery with best possible extent of tumour resection 2. Induction with simultaneous radiochemotherapy: 2.1. Fractionated, locoregional radiotherapy, total dose 54 - 60 Gy 2.2. Simultaneous chemotherapy with oral temozolomide, 7 days per week at 75 mg/m^2/d, starting at day 1 for the entire period of radiotherapy (at maximum 49 days) 3. Consolidation chemotherapy: four weeks after simultaneous radiochemotherapy initiation of a 5 day-course of oral temozolomide [150 - 200 mg/m^2/d], repeated every 28 days for in total 12 courses |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Temozolomide |
| Primary outcome measure | Event-status 6 months after diagnosis: event/no event (i.e. by magnetic resonance imaging). An "event" is defined as: 1. Progression/relapse of disease 2. Diagnosis of a secondary malignancy 3. Death of any cause |
| Secondary outcome measures | 1. Event-free survival defined as time from diagnosis until the first event, measured after 1 year and 2 years 2. Overall survival defined as time from diagnosis until death of any cause, measured after 6 months, 1 year, and 2 years 3. Common Toxicity Criteria (CTC) toxicity levels of treatment elements A follow-up of 2 years after study entry is required, however, a long term follow-up is highly recommended. Thus, event-free survival and overall survival will possibly be evaulated after 5 years and longer. |
| Overall study start date | 01/06/2009 |
| Completion date | 31/12/2017 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Child |
| Lower age limit | 3 Years |
| Upper age limit | 18 Years |
| Sex | Both |
| Target number of participants | 135 |
| Key inclusion criteria | 1. Newly diagnosed, previously untreated high grade glioma with central neuropathological review including glioblastoma multiforme (WHO IV), anaplastic astrocytoma (WHO III), anaplastic oligodendroglioma (WHO III), anaplastic mixed glioma/anaplastic oligoastrocytoma (WHO III), anaplastic pilocytic astrocytoma (WHO III), anaplastic ganglioglioma (WHO III), anaplastic pleomorphic xanthoastrocytoma (WHO III), giant cell glioblastoma (WHO IV), and gliosarcoma (WHO IV) 2. Newly diagnosed, previously untreated diffuse intrinsic pontine glioma of all tumour grades with central neuroradiological review 3. Newly diagnosed, previously untreated gliomatosis cerebri of all tumour grades with central neuropathological review 4. Patient aged 3 years and older but under 18 years at time of diagnosis, either sex 5. Written informed consent of the patient and/or the patient's parents or legal guardian according to national laws |
| Key exclusion criteria | 1. Pre-treatment of glioblastoma multiforme (WHO IV), anaplastic astrocytoma (WHO III), anaplastic oligodendroglioma (WHO III), anaplastic mixed glioma/anaplastic oligoastrocytoma (WHO III), anaplastic pilocytic astrocytoma (WHO III), anaplastic ganglioglioma (WHO III), anaplastic pleomorphic xanthoastrocytoma (WHO III), giant cell glioblastoma (WHO IV), gliosarcoma (WHO IV), diffuse intrinsic pontine glioma and gliomatosis cerebri differing from study protocol 2. Known hypersensitivity or contraindication to study drugs and/or dacarbazine 3. Prior chemotherapy or radiotherapy which prevents adequate performance of radiotherapy as outlined by the present protocol. This may mainly apply to patients with secondary malignant glioma after previous malignant brain tumour, e.g. medulloblastoma, supratentorial PNET. If previous treatment does not prevent the adequate performance of the outlined treatment protocol patients with secondary malignant glioma will be eligible for the present trial. 4. Other (simultaneous) malignancies 5. Pregnancy and/or lactation 6. Patients who are sexually active refusing to use effective contraception (oral contraception, intrauterine devices, barrier method of contraception in conjunction with spermicidal jelly or surgical sterile) 7. Current or recent (within 30 days prior to start of trial treatment) treatment with another investigational drug or participation in another investigational trial 8. Very poor clinical condition as defined by demand of mechanical ventilation and/or demand for intravenous catecholamines and/or very severe neurological damage equivalent to a coma and/or tetraplegia with complete incapability for communication (deafness, blindness, mutism) 9. Severe concomitant diseases (e.g. immune deficiency syndrome) 10. Known human immunodeficiency virus (HIV) positivity Country-specifically very young patients may be excluded to comply with national laws or formal insurance requirements. |
| Date of first enrolment | 10/06/2009 |
| Date of final enrolment | 31/12/2015 |
Locations
Countries of recruitment
- Austria
- Germany
- Switzerland
Study participating centre
University Children's Hospital
Halle
06120
Germany
06120
Germany
Sponsor information
Martin Luther University Halle-Wittenberg (Germany)
University/education
University/education
c/o Dr. Siegfried Bauer
Magdeburgerstr. 8
Halle
06097
Germany
| prodekanat.forschung@medizin.uni-halle.de | |
| Website | http://www.medizin.uni-halle.de/ |
"ROR" |
https://ror.org/05gqaka33 |
Funders
Funder type
Charity
The German Children's Cancer Foundation (Deutsche Kinderkrebsstiftung) (Germany) (ref: DKS 2009.06)
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
