Evaluate the Role of Anthracycline After Radio Therapy in Patients With Glioblastoma (pGBM).

Interventional, Single-arm, Open-label Open-label, Phase II Trial to Evaluate the Role of Anthracycline Infusion After Radio Therapy (RT) in Pediatric and Young Adults With Glioblastoma (pGBM).

Glioblastoma (GBM) and diffuse intrinsic bridge gliomas (DIPG) only the most aggressive forms of cancer, and their prognosis remains bleak. Currently, the standard of treatment is TMZ concomitant with radiotherapy, and, at the end of combined treatment, as adjuvant therapy. In vitro and in vivo experimental studies have suggested that anthracyclines are effective antineoplastics for the treatment of gliomas. In patients with solid tumors treated with anthracyclines, continuous infusion administration compared with bolus administration has been shown to provide a better safety profile especially with regard to cardiotoxicity. Based on this evidence, this study aims to evaluate the safety and antitumor activity of combined treatment with Dox, WBRT (whole body radiotherapy), and TMZ in pediatric and young adult patients affected by GMB

Study Overview

• Status: Recruiting
• Conditions: Glioblastoma
• Intervention / Treatment: Drug: Radiotherapy, Temozolomide, Doxorubicin

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Iacopo Sardi; Phone Number: 0555662631; Email: iacopo.sardi@meyer.it

Study Locations

• Italy
  • Florence, Italy
    • Recruiting
    • Meyer Children's Hospital IRCCS
    • Contact: Iacopo Sardi; Email: iacopo.sardi@meyer.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with histological-molecular diagnosis according to WHO 2016 classification: IDH-wildtype glioblastoma (9440/3), giant cell glioblastoma (9441/3), gliosarcoma (9442/3), epithelioid glioblastoma (9440/3), IDH-mutated glioblastoma (9445/3), glioblastoma NOS (9440/3), diffuse astrocytoma (9400/3), diffuse midline glioma H3 K27M mutated, including multifocal, metastatic or gliomatosis cerebri pictures of first diagnosis Not previously treated (with chemo and radiotherapy) or treated only surgically (total, near partial, partial, biopsy).
• Males and females between the ages of 3 and 30 years old
• Life expectancy ≥ 12 months
• karnofsky/Lansky ≥ 80 %
• Adequate hematologic function: Absolute leukocyte count ≥ 2.0 x 109/l, Hemoglobin ≥ 10 g/dl, Platelet count ≥ 50 x 109/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
• Written informed consent from the patient, parents or legal guardians
• Patient's willingness during treatment and ability to comply with the protocol

Exclusion Criteria:

• Evidence of any other serious disease or condition that is a contraindication to study therapy (e.g. severe mental retardation, severe cerebral palsy, severe syndromes congenital syndromes, heart disease)
• Performance of a course of 1st-line chemotherapy at the same time as study initiation
• Concurrent participation in other research projects
• Pregnancy or lactation status
• Use of inappropriate contraceptive methods

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: pGBM patients therapy; Whole therapy radiation therapy; Temozolomide concomitant; After 1 month adjuvant Temozolomide,; After 3 months Doxorubicine; adjuvant Temozolomide

Drug: Radiotherapy, Temozolomide, Doxorubicin; Radiation treatment Concomitant TMZ: 75mg/m2/day per OS for 7 days per week, from the first day of radiotherapy to the last (maximum cumulative dose 3150mg/m2), with possibility of earlier initiation on clinician's judgment. After 1 month (4-5 weeks ± 7 days) from the end of RT/TMZ treatment they will receive: Adjuvant TMZ: 2 cycles at increasing doses (150-180 mg/m2) per OS for 5 consecutive days 28 days apart After 3 months (12 weeks ± 7 days) from the end of RT/TMZ treatment they will receive: Dox 4 cycles with 37.5mg/m2/day by continuous infusion over 48 hours (2 days) every 28 days (maximum cumulative dose 300mg/m2) And after 4 weeks ± 7 days from the end of Dox treatment they will receive: TMZ adjuvant 12 cycles at increasing doses (150-180 mg/m2) by OS for 5 consecutive days 28 days apart (maximum cumulative dose 16200 mg/m2);

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation prolonged Dox	Time to early withdrawal from experimental treatment with Dox	through study completion, an average of 1 year
Percentage of Withdrawal from the study rate	Percentage of subjects with SAE leading to withdrawal from the study	through study completion, an average of 1 year
Percentage of SAEs	Percentage of SAEs	through study completion, an average of 1 year
Mortality rate	Mortality from adverse events	through study completion, an average of 1 year
Early discontinuation of dox treatment rate	Proportion of early discontinuation of experimental treatment with Dox	through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event-free survival (EFS), disease progression (PFS), and overall survival (OS)	Event-free survival (EFS) calculated as the time between the date of enrolment and the date of occurrence of one of the events: disease progression established according to the modified RANO criteria for paediatric age; clear progression of non-measurable lesions (T1);; - any new lesion;; clinical deterioration due to the tumour and not attributable to other causes (e.g, seizures, adverse drug effects, complications of therapy, cerebrovascular events infections and so on);; failure to return for evaluation following death (from any cause) or deterioration of condition;; and other described in the protocol	through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Iacopo Sardi
• Investigators: Principal Investigator: Iacopo Sardi, Meyer Children's Hospital IRCCS

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2022
• Primary Completion (Estimated): November 9, 2027
• Study Completion (Estimated): March 9, 2028

Study Registration Dates

• First Submitted: February 20, 2024
• First Submitted That Met QC Criteria: February 29, 2024
• First Posted (Actual): March 7, 2024

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: February 29, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Temozolomide; Doxorubicin
• Other Study ID Numbers: pGBM-WBRT/DOX2020

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No