Prolonged Exposure to Doxorubicin in Patients With Glioblastoma Multiforme and Diffuse Intrinsic Pontine Glioma

Meyer Children's Hospital IRCCS

Status and phase: Terminated; Phase 2

Conditions: Gliomatosis Cerebri; Midline Diffuse Glioma; Glioblastoma (GBM); Diffuse Spinal Glioma; Bilateral Thalamic Glioma; Brainstem Glioma, Pediatric; Anaplastic Astrocytoma; DIPG

Treatments: Drug: Doxorubicin

Study type: Interventional

Funder types: Other

Identifiers

NCT02758366

2015-002307-28 (EudraCT Number)

GBMTMZ/DOX2015

Details and patient eligibility

About

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).

Enrollment: 21 patients

Sex: All

Ages: 3 to 30 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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21 participants in 1 patient group

Doxorubicin

Experimental group

Description:

Patients are treated with Weller-Stupp protocol: initial radiotherapy (1.8 Gy/die, days 1-5; total dose 54-60 Gy) with concomitant oral temozolomide (75mg/m2/die, days 1-7) per 6 weeks. At week 10 (4 weeks after the chemo-radiotherapy treatment completion): 1 cycle of oral temozolomide (150-180 mg/m2, days 1-5) At week 14 (8 weeks after the chemo-radiotherapy treatment completion) 1 cycle of prolonged infusion of Doxorubicin (25mg/m2/die in 24 hours, days 1-4; total cumulative dose 100 mg/m2). At week 18 (4 weeks after the end of doxorubicin administration): 16 cycles of oral temozolomide (initial dose of 150 mg/m2 increasing to 180 mg/m2 days 1-5, 28-day cycle). Oral valproic acid (20-30 mg/Kg/die bid) is administered from week 1 until the last treatment day.

Treatment:

Drug: Doxorubicin