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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02758366
Recruitment Status : Terminated (Study was terminated due to high heterogeneity of enrolled patients)
First Posted : May 2, 2016
Last Update Posted : February 9, 2021
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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 21 participants
Allocation: N/A
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)
Actual Study Start Date : February 2016
Actual Primary Completion Date : January 16, 2020
Actual Study Completion Date : January 16, 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

Information from the National Library of Medicine

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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 identifier (NCT number): NCT02758366

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Meyer Children's Hospital
Florence, Italy, 50145
Sponsors and Collaborators
Meyer Children's Hospital

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Responsible Party: Iacopo Sardi, MD, PhD, Meyer Children's Hospital Identifier: NCT02758366    
Other Study ID Numbers: GBMTMZ/DOX2015
2015-002307-28 ( EudraCT Number )
First Posted: May 2, 2016    Key Record Dates
Last Update Posted: February 9, 2021
Last Verified: February 2021
Keywords provided by Iacopo Sardi, Meyer Children's Hospital:
glioblastoma multiforme
high grade glioma
diffuse intrinsic pontine glioma
malignant glioma
Brainstem Glioma
diffuse spinal glioma
bilateral thalamic glioma
Anaplastic Astrocytoma
Gliomatosis Cerebri
Midline Diffuse Glioma
Additional relevant MeSH terms:
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Diffuse Intrinsic Pontine Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Brain Stem Neoplasms
Infratentorial Neoplasms
Brain Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action