RecruitingPhase 2NCT06297512

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).

Sponsor

Iacopo Sardi

Enrollment

20 participants

Start Date

Dec 9, 2022

Study Type

INTERVENTIONAL

Conditions

Glioblastoma

Summary

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

Eligibility

Min Age: 3 YearsMax Age: 30 Years

Inclusion Criteria9

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 Criteria5

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

Interventions

DRUGRadiotherapy, 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);