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

Phase 2

Terminated

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

• Registration Number: NCT02758366
• Lead Sponsor: Meyer Children's Hospital IRCCS

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).

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2016-02
• Study First Submitted: 2016-04-27
• Study First Submitted QC: 2016-04-28
• Study First Posted: 2016-05-02
• Primary Completion: 2020-01-16
• Study Completion: 2020-01-16
• Status Verified: 2021-02
• Last Update Submitted: 2021-02-04
• Last Update Posted: 2021-02-09

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 21

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Doxorubicin	Doxorubicin	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.

Primary Outcome Measures

Name	Time	Method
Time to early discontinuation of the study drug (doxorubicin)	6 months
Number of patients who undergone to withdrawal of doxorubicin	6 months	Rate of early suspension of the study drug (doxorubicin)
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 Outcome Measures

Name	Time	Method
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
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
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

Trial Locations

Locations (1)

Meyer Children's Hospital; 🇮🇹 Florence, Italy