Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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.
 
ClinicalTrials.gov 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
Sponsor:
Information provided by (Responsible Party):
Iacopo Sardi, Meyer Children's Hospital

Tracking Information
First Submitted Date  ICMJE April 27, 2016
First Posted Date  ICMJE May 2, 2016
Last Update Posted Date February 9, 2021
Actual Study Start Date  ICMJE February 2016
Actual Primary Completion Date January 16, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 28, 2016)
  • 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)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 28, 2016)
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Prolonged Exposure to Doxorubicin in Patients With Glioblastoma Multiforme and Diffuse Intrinsic Pontine Glioma
Official Title  ICMJE 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)
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Glioblastoma (GBM)
  • DIPG
  • Brainstem Glioma, Pediatric
  • Diffuse Spinal Glioma
  • Bilateral Thalamic Glioma
  • Gliomatosis Cerebri
  • Anaplastic Astrocytoma
  • Midline Diffuse Glioma
Intervention  ICMJE Drug: Doxorubicin
Study Arms  ICMJE 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.

Intervention: Drug: Doxorubicin
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: February 4, 2021)
21
Original Estimated Enrollment  ICMJE
 (submitted: April 28, 2016)
20
Actual Study Completion Date  ICMJE January 16, 2020
Actual Primary Completion Date January 16, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 3 Years to 30 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02758366
Other Study ID Numbers  ICMJE GBMTMZ/DOX2015
2015-002307-28 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Iacopo Sardi, Meyer Children's Hospital
Study Sponsor  ICMJE Meyer Children's Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Meyer Children's Hospital
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP