Clinical trial NCT02758366: Prolonged Exposure to Doxorubicin in Patients With Glioblastoma Multiforme and Diffuse Intrinsic Pontine Glioma
Official title: An Open-label, Single-arm, Phase II Study to Evaluate Safety and Efficacy of Doxorubicin in Combination With Radiotherapy, Temozolomide and Valproic Acid in Patients With Glioblastoma Multiforme (GBM) and Diffuse Intrinsic Pontine Glioma (DIPG)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Glioblastoma (GBM)
DIPG
Brainstem Glioma, Pediatric
Diffuse Spinal Glioma
Bilateral Thalamic Glioma
Gliomatosis Cerebri
Anaplastic Astrocytoma
Midline Diffuse Glioma
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
Lead sponsor: Meyer Children's Hospital IRCCS
Sponsor class: OTHER
First posted: 2016-05-02
Enrollment: 21
Sex: ALL
Minimum age (years): 3
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

Primary outcomes:
measure: Time to early discontinuation of the study drug (doxorubicin)
timeFrame: 6 months
measure: Number of participants with treatment-related serious adverse events (SAE) as assessed by CTCAE v4.0
timeFrame: 32 months
measure: Number of patients who died for SAE as assessed by CTCAE v4.0
timeFrame: 32 months
measure: Number of patients who undergone to withdrawal of doxorubicin
timeFrame: 6 months
Secondary outcomes:
measure: Event free survival
timeFrame: 2 months
measure: Overall survival
timeFrame: 2 months
measure: Progression free survival
timeFrame: 2 months
measure: Rate of treatment response
timeFrame: 2 months
Other outcomes:
Locations:
city: Florence
country: Italy
facility: Meyer Children's Hospital
Study officials:
References:
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