Prolonged Exposure to Doxorubicin in Patients With Glioblastoma Multiforme and Diffuse Intrinsic Pontine Glioma
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).
|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)|
- 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)
- 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
|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)|
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02758366
|Contact: Iacopo Sardi, MD, PhDfirstname.lastname@example.org|
|Meyer Children's Hospital||Recruiting|
|Florence, Italy, 50145|
|Contact: Iacopo Sardi, MD, PhD +390555662631 email@example.com|