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A study of doxorubicin in combination with radiotherapy, temozolomide and valproic acid in pediatric and adolescent patients with newly diagnosed high grade glioma (glioblastoma multiforme (GBM) and diffuse intrinsic pontine glioma (DIPG)).

Phase 1
Conditions
Glioblastoma multiforme, diffuse intrisic pontine glioma, diffuse glioma of the brain stem and spinal cord, bilateral thalamic glioma, gliomatosis cerebri, anaplastic astrocytoma
MedDRA version: 20.0Level: PTClassification code 10018338Term: GliomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]
Registration Number
EUCTR2015-002307-28-IT
Lead Sponsor
AZIENDA OSPEDALIERO-UNIVERSITARIA MEYER
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
Sex
All
Target Recruitment
20
Inclusion Criteria

Males and females patients, aged >3 years and < 30 years;
Histologically confirmed newly diagnosed glioblastoma multiforme, diffuse intrisic pontine glioma, diffuse glioma of the brain stem and spinal cord, bilateral thalamic glioma, gliomatosis cerebri, anaplastic astrocytoma;
Patients undergone either surgery or biopsy only;
No prior chemotherapy and/or radiotherapy;
Life expectancy = 4 weeks;
Karnofsky/Lansky = 40 %;
Written informed consent obtained from the patient/parents or legal representative;
Adequate hematological function (leucocyte = 2.0 x 10^9/l - Hemoglobin = 10 g/dl - platelet = 50 x 10^9 /l);
Adequate liver function (total bilirubin = 2.5 x ULN - ALT/AST = 5.0 x ULN);
Adequate renal function (serum creatinine = 1.5 x ULN);
Availability to trial treatment and ability to be compliant with the protocol

Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 2
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Any disease or condition that contraindicates the use of the study treatment (es. serious mental retardation, brain palsy, congenital syndrome, cardiomyopathy)
Prior anti-cancer therapy
Pregnancy or breastfeeding
Non adequate contraception

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Main Objective: To assess safety and tolerability of continuous infusion of doxorubicin when added to standard therapy in pediatric and adult patients with newly diagnosed glioblastoma multiforme, diffuse intrisic pontine glioma, diffuse glioma of the brain stem and spinal cord, bilateral thalamic glioma, gliomatosis cerebri, anaplastic astrocytoma;Secondary Objective: To evaluate efficacy of the treatment through assessment of event free survival (EFS) defined as tumor progression, tumor recurrence and death attributable to any cause, and overall survival (OS).;Primary end point(s): Primary safety end points: <br>-Time to early discontinuation of the experimental treatment (doxorubicin) <br>-Percentage of subjects with SAE leading to withdrawal from the study <br>-Percentage of SAE <br>-Mortality due to adverse events <br>-Rate of early suspension of experimental treatment with doxorubicin;Timepoint(s) of evaluation of this end point: 6 months
Secondary Outcome Measures
NameTimeMethod
Secondary end point(s): Secondary efficacy end points:<br>-Event free survival (EFS) defined as time frame between the date of enrolment and the earliest occurence of anyone of the following: progression based on RECIST 1.1 criteria; tumor recurrence; death to any cause.<br>-Overall survival (OS) defined as time frame between the date of the enrolment and the death to any cause<br>-Progression free survival (PFS) defined as time frame between the date of the enrolment and the date tumor progression based on RECIST 1.1 criteria<br>-Rate of treatment response (CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease) based on RECIST 1.1 criteria;Timepoint(s) of evaluation of this end point: Every 2 months
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