E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of relapsed or refractory high grade gliomas and diffuse intrinsic pontine gliomas in paediatric patients ≥ 3 years and < 18 years of age. |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10002224 |
E.1.2 | Term | Anaplastic astrocytoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10030288 |
E.1.2 | Term | Oligodendroglioma malignant |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10065443 |
E.1.2 | Term | Malignant glioma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10060971 |
E.1.2 | Term | Astrocytoma malignant |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10017701 |
E.1.2 | Term | Ganglioglioma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10018337 |
E.1.2 | Term | Glioblastoma multiforme |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003572 |
E.1.2 | Term | Astrocytoma malignant NOS |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10018336 |
E.1.2 | Term | Glioblastoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008093 |
E.1.2 | Term | Cerebral astrocytoma, high grade |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10026659 |
E.1.2 | Term | Malignant oligodendroglioma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10018340 |
E.1.2 | Term | Gliosarcoma |
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 efficacy of a combined treatment with Cilengitide and metronomic oral Temozolomide in children and adolescents with relapsed or refractory high-grade malignant glioma and diffuse intrinsic pontine glioma, as indicated by 6 months overall survival (OS) after diagnosis of relapse or tumour progression, in comparison to a historical control group of paediatric HGG relapse patients from the HIT-GBM/HIT-HGG data base. |
|
E.2.2 | Secondary objectives of the trial |
1. To evaluate the safety and toxicity of the study treatment by common toxicity criteria (CTC; version 4.0).
2. To assess
- the response rates at 6 months (continuous complete response = CCR, complete response = CR, partial response = PR, stable disease = SD, progressive disease = PD) and
- progression-free survival (PFS) at 6 months, and
- response rates, OS, and PFS at 12 months
after relapse diagnosis or diagnosis of tumor progression.
Response will be presented including histopathological variants.
3. To assess the pharmacokinetics of cilengitide administered as part of the study treatment.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Diagnosis of high-grade malignant glioma confirmed by central neuropathological review (last MRI diagnosis not older than 4 weeks) - including glioblastoma multiforme (WHO IV), anaplastic astrocytoma (WHO III), anaplastic oligodendroglioma (WHO III), anaplastic oligoastrocytoma (WHO III), anaplastic pilocytic astrocytoma (WHO III), anaplastic ganglioglioma (WHO III), anaplastic pleomorphic xanthoastrocytoma (analogous to WHO III), giant cell glioblastoma (WHO IV), and gliosarcoma (WHO IV) - or diagnosis of diffuse intrinsic pontine glioma confirmed by central neuroradiological review - refractory to standard treatment, or relapsed or progressive after first-line therapy.
2. Patient aged 3 years and older but under 18 years at time of relapse diagnosis
3. Written informed consent of the patient (mandatory from 15 years of age) or the parents (mandatory till 18 years of age). |
|
E.4 | Principal exclusion criteria |
1. Known hypersensitivity or contraindication to any study drugs
2. Other (simultaneous) malignancies
3. Pregnancy and / or lactation
4. 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)
5. Current or recent (within 30 days prior to start of trial treatment) treatment with another investigational drug or participation in another investigational trial
6. Severe concomitant diseases (e.g. immune deficiency syndrome) or HIV infection
7. Severe psychological disease or neurological damage without possibility to communicate
8. Clinical signs of intracranial pressure
9. Intracerebral hemorrhage or history of intracerebral hemorrhage
10. Following laboratory test results (not older than 2 weeks before patient´s inclusion):
•Platelets < 100 000/µl (< 100 Gpt/l)
•PT, INR and PTT above normal range
•Absolute neutrophil count ≤ 1 500/µl (< 1,5 Gpt/l)
•Hemoglobin < 10g/dl (< 6,4 mmol/L)
•Serum creatinine ≥ 1,5 x upper limit of normal range or creatinine clearance rate ≤ 60 ml/min/m2 (corrected for body surface area)
•Total bilirubin ≥ 1,5 x upper limit of normal range
•SGOT (ASAT) and SGPT (ALAT) ≥ 2,5 x upper limit of normal range
•Alkaline phosphatase ≥ 2,5 x upper limit of normal range
11. Hereditary Intrinsic Platelet Disorders
12.Ongoing irradiation or chemotherapy (within the last 4 weeks)
13. Estimated life expectancy of less than 2 months |
|
E.5 End points |
E.5.1 | Primary end point(s) |
6 month OS rate after diagnosis of relapse or tumour progression |
|
E.5.2 | Secondary end point(s) |
1. Safety and toxicity according to NCI CTC, version 4.0)
2. Response rates (CCR, CR, PR, SD, PD) and PFS at 6 months and response rates, PFS, and OS at 12 months after diagnosis of relapse or tumour progression
3. Pharmacokinetics of cilengitide in the study population
|
|
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 | Yes |
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 | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
historical study population from the HIT-GBM data base |
|
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 | Yes |
E.8.2.3.1 | Comparator description |
historical study population from the HIT-GBM data base |
|
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 | 54 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 54 |
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
|
The recruitment period for the trial will last 24 months. Individual
follow-up for at least 1 year after study entry is required for this
protocol. The study will be finished 30 days after completion of study
treatment of the last patient enrolled. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 30 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
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 | 30 |