ivolumab in combination with temozolomide and radiotherapy in children and adolescents with newly diagnosed high-grade glioma
- Conditions
- ewly diagnosed High-Grade Gliomas (HGG)MedDRA version: 20.0 Level: PT Classification code 10065443 Term: Malignant glioma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0 Level: PT Classification code 10018338 Term: Glioma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-002688-24-FR
- Lead Sponsor
- Gustave Roussy
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 40
1.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
2.Age at inclusion: ? 3 to <18 years of age
3.Patients should be able and willing to comply with study visits and procedures as per protocol.
4.Patients must be affiliated to a social security system or beneficiary of the same according to local requirements
5.Sexually actice 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. Acceptable contraception is listed in Appendix 7.
6.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 pleïomorphic astrocytoma will be eligible.
7.Local histological diagnosis has been confirmed centrally by a designated reference pathologist.
8.Able to commence trial treatment within 6 weeks following the last major surgery.
9.Adequate Bone Marrow Function : Hemoglobin ? 10 g/dL (transfusion independent), Neutrophil count ? 1.0 ? 109/L. Platelet count ? 100 ? 109/L (transfusion independent)
10.Absence of Coagulation Disorder
11.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
12.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
Are the trial subjects under 18? yes
Number of subjects for this age range: 40
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
1.Any disease or condition that contraindicates the use of the study medication/treatment (for TMZ, see the approved product labelling) or places the patient at an unacceptable risk of experiencing treatment related complications.
2.Patients should not be on high-dose steroids (ie > 1mg/kg) before study entry; doses should be stable for at least two weeks or decreasing.
3.Low probability of protocol compliance.
4.Radiological evidence of surgically related intracranial bleeding (excluding asymptomatic, resolving hemorrhagic changes associated with recent surgery and the presence of punctuate hemorrhage in the tumor).
5.Subjects with concommitant second malignanices are excluded unless a complete remission is achieved as it is empirically determined based on the malignancy and treatment provided prior to study entry and no additional therapy is required or anticipated to be required during the study period.
6.Previous cranial irradiation.
7.Any known auto-immune disease, previous or ongoing.
8.Known chronic inflammatory digestive disease, previous or ongoing.
9.Chronic asthma receiving corticotherapy, even only with inhalation.
10.Vaccinated with live attenuated vaccines within 4 weeks of the first dose of study drug
11.Pregnant or breastfeeding women
12.Known hypersensitivity to any component of the products (study drug or ingredients)
13.Clinically significant, uncontrolled heart disease (including history of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality within 12 months of screening).
14.Patients who are currently receiving another investigational drug or anticancer agent
15.Patient who have an uncontrolled infection
16.Patient with known human immunodeficiency virus (HIV) / AIDS infection or acute / chronic Hepatitis B or C
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective will be to evaluate the feasability of nivolumab administration when added to postoperative radiotherapy with concomitant and adjuvant temozolomide and to determine whether the addition of nivolumab to the initial management of pediatric patients with newly diagnosed supratentorial high-grade glioma shows a signal of clinical benefit.;<br> Secondary Objective: i)To assess clinical benefit with alternative efficacy outcomes<br> ii)To assess response to treatment<br><br> ;<br> Primary end point(s): Assessment of Toxicity and Safety according to NCI – CTCAE v5.0 (proportion of DLT)<br> ;Timepoint(s) of evaluation of this end point: First 6 weeks
- Secondary Outcome Measures
Name Time Method <br> Secondary end point(s): i)1-year Overall Survival (OS)<br> ii)6 month EFS,<br> iii)Best response rate according to the RANO criteria. When the pediatric criteria will be available, they will be incorporated in the response assessment<br> iv)Immune-related response criteria (irRC)<br> ;Timepoint(s) of evaluation of this end point: 12 months after the end of treatment