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

NCT ID: NCT06297512

Last Updated: 2024-03-07

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-12-09
• Study Completion Date: 2028-03-09

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

pGBM patients therapy

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

Group Type: EXPERIMENTAL

Radiotherapy, Temozolomide, Doxorubicin

Intervention Type: 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);

Interventions

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);

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Iacopo Sardi

OTHER

Sponsor Role: lead

Responsible Party

Iacopo Sardi

Princiapl Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Iacopo Sardi

Role: PRINCIPAL_INVESTIGATOR

Meyer Children's Hospital IRCCS

Locations

Meyer Children's Hospital IRCCS

Florence, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Iacopo Sardi

Role: CONTACT

iacopo.sardi@meyer.it

0555662631

Facility Contacts

Iacopo Sardi

Role: primary

iacopo.sardi@meyer.it

Other Identifiers

pGBM-WBRT/DOX2020

Identifier Type: -

Identifier Source: org_study_id