Anaplastic Astrocytoma, Bilateral Thalamic Glioma, Brainstem Glioma, Pediatric, Diffuse Spinal Glioma, DIPG, Glioblastoma (GBM), Gliomatosis Cerebri, Midline Diffuse Glioma
Conditions
Keywords
glioblastoma multiforme, high grade glioma, diffuse intrinsic pontine glioma, DIPG, doxorubicin, temozolomide, malignant glioma, Brainstem Glioma, diffuse spinal glioma, bilateral thalamic glioma, Anaplastic Astrocytoma, Gliomatosis Cerebri, Midline Diffuse Glioma
Brief summary
The standard therapy of glioblastoma (GBM) consists of gross total resection followed by focal irradiation to the tumor bed with concomitant and adjuvant temozolomide (TMZ). The association of valproic acid and TMZ during radiotherapy improves survival of GBM. Preclinical studies suggested that doxorubicin had a strong antineoplastic activity against human gliomas. Moreover, some studies showed that the continuous infusion of anthracyclines in patients with solid tumor ensured a better safety profile compared with bolus administration. Based on these findings, the purpose of this study is to evaluate safety and efficacy of prolonged administration of doxorubicin in combination with radiotherapy, temozolomide and valproic acid in pediatric and adult patients with newly diagnosed GBM and diffuse intrinsic pontine glioma (DIPG).
Interventions
DRUGDoxorubicin
Sponsors
Meyer Children's Hospital IRCCS
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 30 Years
Healthy volunteers
No
Inclusion criteria
* Males and females patients, aged \>3 years and \< 30 years; * Newly diagnosed of GBM, DIPG, diffuse brainstem glioma, diffuse spinal glioma, 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); * Adherence to trial treatment and compliance with the protocol
Exclusion criteria
* Any disease or condition that contraindicates the use of the study drug (es. serious mental retardation, brain palsy, congenital syndrome, cardiomyopathy) * Prior anti-cancer therapy * Pregnancy or breastfeeding * Non adequate contraception
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of patients who undergone to withdrawal of doxorubicin | 6 months | Rate of early suspension of the study drug (doxorubicin) |
| Time to early discontinuation of the study drug (doxorubicin) | 6 months | — |
| Number of participants with treatment-related serious adverse events (SAE) as assessed by CTCAE v4.0 | 32 months | Number of patients with SAE and SAE leading to withdrawal from the study |
| Number of patients who died for SAE as assessed by CTCAE v4.0 | 32 months | Mortality due to adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Event free survival | 2 months | Event free survival (EFS) defined as time (days) 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. |
| Overall survival | 2 months | Overall survival (OS) defined as time between the date of the enrolment and the death to any cause |
| Progression free survival | 2 months | Progression free survival (PFS) defined as time between the date of the enrolment and the date tumor progression based on RECIST 1.1criteria |
| Rate of treatment response | 2 months | Rate of treatment response (CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease) based on RECIST 1.1 criteria |
Countries
Italy
Outcome results
None listed