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

Primary Purpose

Glioblastoma (GBM), DIPG, Brainstem Glioma, Pediatric

Status
Terminated
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Doxorubicin
Sponsored by
Meyer Children's Hospital IRCCS
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glioblastoma (GBM) focused on measuring glioblastoma multiforme, high grade glioma, diffuse intrinsic pontine glioma, DIPG, doxorubicin, temozolomide, malignant glioma, Brainstem Glioma, diffuse spinal glioma, bilateral thalamic glioma, Anaplastic Astrocytoma, Gliomatosis Cerebri, Midline Diffuse Glioma

Eligibility Criteria

3 Years - 30 Years (Child, Adult)All SexesDoes not accept 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

Sites / Locations

  • Meyer Children's Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Doxorubicin

Arm 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.

Outcomes

Primary Outcome Measures

Time to early discontinuation of the study drug (doxorubicin)
Number of participants with treatment-related serious adverse events (SAE) as assessed by CTCAE v4.0
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
Mortality due to adverse events
Number of patients who undergone to withdrawal of doxorubicin
Rate of early suspension of the study drug (doxorubicin)

Secondary Outcome Measures

Event free survival
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
Overall survival (OS) defined as time between the date of the enrolment and the death to any cause
Progression free survival
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
Rate of treatment response (CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease) based on RECIST 1.1 criteria

Full Information

First Posted
April 27, 2016
Last Updated
February 4, 2021
Sponsor
Meyer Children's Hospital IRCCS
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1. Study Identification

Unique Protocol Identification Number
NCT02758366
Brief Title
Prolonged Exposure to Doxorubicin in Patients With Glioblastoma Multiforme and Diffuse Intrinsic Pontine Glioma
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 Type
Interventional

2. Study Status

Record Verification Date
February 2021
Overall Recruitment Status
Terminated
Why Stopped
Study was terminated due to high heterogeneity of enrolled patients
Study Start Date
February 2016 (Actual)
Primary Completion Date
January 16, 2020 (Actual)
Study Completion Date
January 16, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Meyer Children's Hospital IRCCS

4. Oversight

Data Monitoring Committee
No

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma (GBM), DIPG, Brainstem Glioma, Pediatric, Diffuse Spinal Glioma, Bilateral Thalamic Glioma, Gliomatosis Cerebri, Anaplastic Astrocytoma, Midline Diffuse Glioma
Keywords
glioblastoma multiforme, high grade glioma, diffuse intrinsic pontine glioma, DIPG, doxorubicin, temozolomide, malignant glioma, Brainstem Glioma, diffuse spinal glioma, bilateral thalamic glioma, Anaplastic Astrocytoma, Gliomatosis Cerebri, Midline Diffuse Glioma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
21 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Doxorubicin
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Doxorubicin
Primary Outcome Measure Information:
Title
Time to early discontinuation of the study drug (doxorubicin)
Time Frame
6 months
Title
Number of participants with treatment-related serious adverse events (SAE) as assessed by CTCAE v4.0
Description
Number of patients with SAE and SAE leading to withdrawal from the study
Time Frame
32 months
Title
Number of patients who died for SAE as assessed by CTCAE v4.0
Description
Mortality due to adverse events
Time Frame
32 months
Title
Number of patients who undergone to withdrawal of doxorubicin
Description
Rate of early suspension of the study drug (doxorubicin)
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Event free survival
Description
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.
Time Frame
2 months
Title
Overall survival
Description
Overall survival (OS) defined as time between the date of the enrolment and the death to any cause
Time Frame
2 months
Title
Progression free survival
Description
Progression free survival (PFS) defined as time between the date of the enrolment and the date tumor progression based on RECIST 1.1criteria
Time Frame
2 months
Title
Rate of treatment response
Description
Rate of treatment response (CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease) based on RECIST 1.1 criteria
Time Frame
2 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
3 Years
Maximum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Meyer Children's Hospital
City
Florence
ZIP/Postal Code
50145
Country
Italy

12. IPD Sharing Statement

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

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