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

This study is currently recruiting participants.
See Contacts and Locations
Verified April 2016 by Iacopo Sardi, Meyer Children's Hospital
Sponsor:
Information provided by (Responsible Party):
Iacopo Sardi, Meyer Children's Hospital
ClinicalTrials.gov Identifier:
NCT02758366
First received: April 27, 2016
Last updated: April 28, 2016
Last verified: April 2016
  Purpose

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 Intervention Phase
Glioblastoma (GBM) DIPG Drug: Doxorubicin Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: 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)

Resource links provided by NLM:


Further study details as provided by Iacopo Sardi, Meyer Children's Hospital:

Primary Outcome Measures:
  • Time to early discontinuation of the study drug (doxorubicin) [ Time Frame: 6 months ]
  • 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

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

  • 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:
  • 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.

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

  • 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

  • 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


Estimated Enrollment: 20
Study Start Date: February 2016
Estimated Study Completion Date: July 2020
Estimated Primary Completion Date: July 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Doxorubicin

Patients with new diagnose of GBM and DIPG are treated with Weller-Stupp protocol: initial radiotherapy (1.8 Gy/die, days 1-5; total dose 54 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): 3 cycles of prolonged infusion of Doxorubicin (25mg/m2/die in 24 hours, days 1-4, 28-day cycle; total cumulative dose 300 mg/m2).

At week 12: 18 cycles of oral temozolomide (initial dose of 150 mg/m2 increasing to 180 mg/m2 days 1-5, 28-day cycle; total cumulative dose 16200 mg/m2).

Oral valproic acid (20-30 mg/Kg/die bid) is administered from week 1 until the last treatment day.

Drug: Doxorubicin

  Eligibility

Ages Eligible for Study:   3 Years to 30 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Males and females patients, aged >3 years and < 30 years;
  • Histologically confirmed newly diagnosed GBM and MRI T2-scans confirmed DIPG;
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02758366

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

Locations
Italy
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
  More Information

Publications:

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 )
Study First Received: April 27, 2016
Last Updated: April 28, 2016

Keywords provided by Iacopo Sardi, Meyer Children's Hospital:
glioblastoma multiforme
high grade glioma
diffuse intrinsic pontine glioma
DIPG
doxorubicin
temozolomide
malignant glioma

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

ClinicalTrials.gov processed this record on June 23, 2017