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

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ClinicalTrials.gov Identifier: NCT02758366
Recruitment Status : Recruiting
First Posted : May 2, 2016
Last Update Posted : February 15, 2018
Information provided by (Responsible Party):
Iacopo Sardi, Meyer Children's Hospital

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).

Condition or disease Intervention/treatment Phase
Glioblastoma (GBM) DIPG Brainstem Glioma, Pediatric Diffuse Spinal Glioma Bilateral Thalamic Glioma Gliomatosis Cerebri Anaplastic Astrocytoma Midline Diffuse Glioma Drug: Doxorubicin Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : February 2016
Estimated Primary Completion Date : July 2020
Estimated Study Completion Date : July 2020

Arm Intervention/treatment
Experimental: 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.

Drug: Doxorubicin

Primary Outcome Measures :
  1. Time to early discontinuation of the study drug (doxorubicin) [ Time Frame: 6 months ]
  2. Number of participants with treatment-related serious adverse events (SAE) as assessed by CTCAE v4.0 [ Time Frame: 32 months ]
    Number of patients with SAE and SAE leading to withdrawal from the study

  3. Number of patients who died for SAE as assessed by CTCAE v4.0 [ Time Frame: 32 months ]
    Mortality due to adverse events

  4. Number of patients who undergone to withdrawal of doxorubicin [ Time Frame: 6 months ]
    Rate of early suspension of the study drug (doxorubicin)

Secondary Outcome Measures :
  1. Event free survival [ Time Frame: 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.

  2. Overall survival [ Time Frame: 2 months ]
    Overall survival (OS) defined as time between the date of the enrolment and the death to any cause

  3. Progression free survival [ Time Frame: 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

  4. Rate of treatment response [ Time Frame: 2 months ]
    Rate of treatment response (CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease) based on RECIST 1.1 criteria

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Ages Eligible for Study:   3 Years to 30 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02758366

Contact: Iacopo Sardi, MD, PhD +390555662631 iacopo.sardi@meyer.it

Meyer Children's Hospital Recruiting
Florence, Italy, 50145
Contact: Iacopo Sardi, MD, PhD    +390555662631    iacopo.sardi@meyer.it   
Sponsors and Collaborators
Meyer Children's Hospital


Responsible Party: Iacopo Sardi, MD, PhD, Meyer Children's Hospital
ClinicalTrials.gov Identifier: NCT02758366     History of Changes
Other Study ID Numbers: GBMTMZ/DOX2015
2015-002307-28 ( EudraCT Number )
First Posted: May 2, 2016    Key Record Dates
Last Update Posted: February 15, 2018
Last Verified: February 2018

Keywords provided by Iacopo Sardi, Meyer Children's Hospital:
diffuse intrinsic pontine glioma
glioblastoma multiforme
high grade glioma
malignant glioma
Brainstem Glioma
diffuse spinal glioma
bilateral thalamic glioma
Anaplastic Astrocytoma
Gliomatosis Cerebri
Midline Diffuse Glioma

Additional relevant MeSH terms:
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Liposomal doxorubicin
Valproic Acid
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Alkylating Agents
GABA Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs