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| ID | Type | Description | Link |
|---|---|---|---|
| 2019/2797 | Other Identifier | CSET number |
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Multicenter, open label, prospective study including successively a phase I trial and then a phase II trial Phase I : Open label, non-randomized, safety run study in nine patients. In case of safety issue a -1 dose level will be tested.
Phase II : Open label, non randomized, efficacy study of nivolumab in addition to radiotherapy and temozolomide. This phase will start when the RP2D has been defined after the last patients evaluable for DLT achieved the first 6 weeks of treatment (the radio-chemotherapy period) with a DLT rate below 30% during the the phase I study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| newly diagnosed high-grade glioma | Experimental | Phase I : Open label, non-randomized, safety run study in nine patients. In case of safety issue a -1 dose level will be tested. Phase II : Open label, non randomized, efficacy study of nivolumab in addition to radiotherapy and temozolomide. This phase will start when the RP2D has been defined after the last patients evaluable for DLT achieved the first 6 weeks of treatment (the radio-chemotherapy period) with a DLT rate below 30% during the the phase I study. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Nivolumab | Drug | Solution for intravenous injection 10 mg/ml. Initial dose : 3 mg/kg Nivolumab will be given at 3 mg/kg/injection every two weeks from the first day of radiotherapy to the last day of chemotherapy. One de-escalation dose : 1 mg/kg |
| Measure | Description | Time Frame |
|---|---|---|
| Event Free Survival | The clinical activity of the combined treatment will be evaluated by the 1-year event free survival (EFS) |
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Inclusion Criteria:
Written informed consent from parents/legal representative, patient, and age-appropriate assent before any study-specific screening procedures are conducted according to local, regional or national guidelines
Age at inclusion: >/= 3 to <18 years of age
Patients should be able and willing to comply with study visits and procedures as per protocol.
Patients must be affiliated to a social security system or beneficiary of the same according to local requirements
Sexually active females of childbearing potential must have a negative serum pregnancy test within 24 hours prior to initiation of treatment. Sexually active women of childbearing potential must agree to use acceptable and appropriate contraception during the study and for at least 5 months after the last study treatment administration. Sexually active males patients (and their female partner) must agree to use condom during the study and for at least 7 months after the last study treatment administration.
Newly diagnosed non-brainstem WHO grade III and IV HGG and neuroglial tumors; gliomatosis cerebri or diffuse glioma, metastatic malignant glial tumors, multifocal gliomas and bithalamic gliomas are eligible for the study. Diffuse midline gliomas with H3K27M mutation are not eligible. Anaplastic ganglioglioma and anaplastic pleomorphic astrocytoma will be eligible.
Local histological diagnosis after either stereotactic biopsy or surgical procedure has been confirmed centrally by a designated reference pathologist.
Able to commence trial treatment within 6 weeks following the last major surgery.
Adequate Bone Marrow Function : Hemoglobin >/= 10 g/dL (transfusion independent), Neutrophil count >/= 1.0 x 10^9/L.
Platelet count >/= 1.0 x 10^9/L (transfusion independent)
Absence of Coagulation Disorder
Adequate Liver Function : AST </= 2.5x institutional ULN for age, ALT </= 2.5x institutional ULN for age, Total Bilirubin </= 1.5x institutional ULN for age
Adequate Renal Function : Serum creatinine must be </= 1.5x ULN for age, absence of clinically significant proteinuria as defined by a screening early morning urine (first sample) dipstick urinalysis of </= 2
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Gustave Roussy | Villejuif | Val De Marne | 94800 | France | ||
| CHU Angers |
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Multicenter, open label, prospective study including successively a phase I trial and then a phase II trial
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| Temozolomide | Drug | Capsules: 5, 20, 100, 140, 180 and 250 mg orally. Temozolomide will be given at 75mg/m2/day from the day of start of radiotherapy to the last day of radiotherapy, then, after one month rest at 200mg/m2/day for five consecutive days for 12 cycles (28 days cycle). |
|
| Radiotherapy | Radiation | Total dose of 54 Gray(Gy) units delivered in 30 daily fractions of 1.8 Gy over 6 weeks during the chemoradiation period. |
|
| Angers |
| 49100 |
| France |
| Centre Oscar Lambret | Lille | 59000 | France |
| Centre Léon Bérard | Lyon | 69008 | France |
| Institut Curie | Paris | 75005 | France |
| CHU Hautepierre | Strasbourg | 67200 | France |
| Hôpital des enfants | Toulouse | 31300 | France |
| ID | Term |
|---|---|
| D005910 | Glioma |
| ID | Term |
|---|---|
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
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| ID | Term |
|---|---|
| D000077594 | Nivolumab |
| D000077204 | Temozolomide |
| D011878 | Radiotherapy |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D003606 | Dacarbazine |
| D014226 | Triazenes |
| D009930 | Organic Chemicals |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D013812 | Therapeutics |
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