Clinical trial · Interventional
Prolonged Exposure to Doxorubicin in Patients With Glioblastoma Multiforme and Diffuse Intrinsic Pontine Glioma
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)
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Why stopped (as posted): Study was terminated due to high heterogeneity of enrolled patients
Summary
Brief summary (as posted)
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).
Conditions
Conditions (8)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Anaplastic Astrocytoma | Anaplastic Astrocytoma | CURATED_BROADER | 0.80 |
| Bilateral Thalamic Glioma | Thalamic Glioma | CURATED_BROADER | 0.78 |
| Brainstem Glioma, Pediatric | Childhood Brain Stem Glioma | ALIAS | 0.90 |
| Diffuse Spinal Glioma | — | UNRESOLVED | — |
| DIPG | Diffuse Intrinsic Pontine Glioma | ALIAS | 0.90 |
| Glioblastoma (GBM) | Glioblastoma | CURATED_BROADER | 0.80 |
| Gliomatosis Cerebri | Gliomatosis Cerebri | ONTOLOGY_EXACT | 0.90 |
| Midline Diffuse Glioma | — | UNRESOLVED |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Doxorubicin | Drug | Doxorubicin | ALIAS |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- Doxorubicin
- description
- Patients are treated with Weller-Stupp protocol: initial radiotherapy (1.8 Gy/die, days 1-5; total dose 54-60 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): 1 cycle of oral temozolomide (150-180 mg/m2, days 1-5) At week 14 (8 weeks after the chemo-radiotherapy treatment completion) 1 cycle of prolonged infusion of Doxorubicin (25mg/m2/die in 24 hours, days 1-4; total cumulative dose 100 mg/m2). At week 18 (4 weeks after the end of doxorubicin administration): 16 cycles of oral temozolomide (initial dose of 150 mg/m2 increasing to 180 mg/m2 days 1-5, 28-day cycle). Oral valproic acid (20-30 mg/Kg/die bid) is administered from week 1 until the last treatment day.
- interventionNames
- Drug: Doxorubicin
Primary outcomes (4)
- measure
- Time to early discontinuation of the study drug (doxorubicin)
- timeFrame
- 6 months
- measure
- Number of participants with treatment-related serious adverse events (SAE) as assessed by CTCAE v4.0
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 3 Years
- Maximum age
- 30 Years
Show eligibility criteria text
Inclusion Criteria: * Males and females patients, aged \>3 years and \< 30 years; * Newly diagnosed of GBM, DIPG, diffuse brainstem glioma, diffuse spinal glioma, bilateral thalamic glioma, gliomatosis cerebri, anaplastic astrocytoma; * Patients undergone either surgery or biopsy only; * No prior chemotherapy and/or radiotherapy; * Life expectancy ≥ 4 weeks; * Karnofsky/Lansky ≥ 40 %; * Written informed consent obtained from the patient/parents or legal representative; * Adequate hematological function (leucocyte ≥ 2.0 x 10\^9/l -Hemoglobin ≥ 10 g/dl - platelet ≥ 50 x 10\^9 /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); * Adherence to trial treatment and compliance with the protocol Exclusion Criteria: * Any disease or condition that contraindicates the use of the study drug (es. serious mental retardation, brain palsy, congenital syndrome, cardiomyopathy) * Prior anti-cancer therapy * Pregnancy or breastfeeding * Non adequate contraception
References
Publications (12)
- BACKGROUNDEramo A, Ricci-Vitiani L, Zeuner A, Pallini R, Lotti F, Sette G, Pilozzi E, Larocca LM, Peschle C, De Maria R. Chemotherapy resistance of glioblastoma stem cells. Cell Death Differ. 2006 Jul;13(7):1238-41. doi: 10.1038/sj.cdd.4401872. Epub 2006 Feb 3. No abstract available. PMID 16456578
- BACKGROUNDStupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005 Mar 10;352(10):987-96. doi: 10.1056/NEJMoa043330. PMID 15758009
- BACKGROUNDAnanda S, Nowak AK, Cher L, Dowling A, Brown C, Simes J, Rosenthal MA; Cooperative Trials Group for Neuro-Oncology (COGNO). Phase 2 trial of temozolomide and pegylated liposomal doxorubicin in the treatment of patients with glioblastoma multiforme following concurrent radiotherapy and chemotherapy. J Clin Neurosci. 2011 Nov;18(11):1444-8. doi: 10.1016/j.jocn.2011.02.026. Epub 2011 Aug 2. PMID 21813279
- BACKGROUNDBeier CP, Schmid C, Gorlia T, Kleinletzenberger C, Beier D, Grauer O, Steinbrecher A, Hirschmann B, Brawanski A, Dietmaier C, Jauch-Worley T, Kolbl O, Pietsch T, Proescholdt M, Rummele P, Muigg A, Stockhammer G, Hegi M, Bogdahn U, Hau P. RNOP-09: pegylated liposomal doxorubicine and prolonged temozolomide in addition to radiotherapy in newly diagnosed glioblastoma--a phase II study. BMC Cancer. 2009 Sep 2;9:308. doi: 10.1186/1471-2407-9-308. PMID 19725960
- BACKGROUNDCohen KJ, Heideman RL, Zhou T, Holmes EJ, Lavey RS, Bouffet E, Pollack IF. Temozolomide in the treatment of children with newly diagnosed diffuse intrinsic pontine gliomas: a report from the Children's Oncology Group. Neuro Oncol. 2011 Apr;13(4):410-6. doi: 10.1093/neuonc/noq205. Epub 2011 Feb 22. PMID 21345842