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

NCT06297512 | Recruiting Phase 2

• 1 other identifier: pGBM-WBRT/DOX2020
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Glioblastoma

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (1)

• Event-free survival (EFS), disease progression (PFS), and overall survival (OS)

  through study completion, an average of 1 year

Study Arms (1)

pGBM patients therapy

EXPERIMENTAL

* Whole therapy radiation therapy * Temozolomide concomitant * After 1 month adjuvant Temozolomide, * After 3 months Doxorubicine * adjuvant Temozolomide

Drug: Radiotherapy, Temozolomide, Doxorubicin

Interventions

Radiotherapy, Temozolomide, Doxorubicin DRUG

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);

pGBM patients therapy

Eligibility Criteria

• Age: 3 Years - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Iacopo Sardi: lead

Study Sites (1)

Meyer Children's Hospital IRCCS

Florence, Italy

RECRUITING

MeSH Terms

Conditions

Glioblastoma

Interventions

Radiotherapy; Temozolomide; Doxorubicin

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Therapeutics; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Iacopo Sardi

  Meyer Children's Hospital IRCCS

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Iacopo Sardi

CONTACT

0555662631; iacopo.sardi@meyer.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Princiapl Investigator

Study Record Dates

• First Submitted: February 20, 2024
• First Posted: March 7, 2024
• Study Start: December 9, 2022
• Primary Completion (Estimated): November 9, 2027
• Study Completion (Estimated): March 9, 2028
• Last Updated: March 7, 2024

Record last verified: 2024-02

Locations

IT (1)