NCT02758366

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)

Terminated Phase 2 Last updated 4 February 2021

What this trial tests

Phase 2 trial testing Doxorubicin in Glioblastoma (GBM) in 21 participants. Terminated before completion.

Timeline

1 February 2016

Primary endpoint
16 January 2020

16 January 2020

Quick facts

Lead sponsor	Meyer Children's Hospital IRCCS
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	21
Start date	1 February 2016
Primary completion	16 January 2020
Estimated completion	16 January 2020
Sites	1 location across Italy

Drugs / interventions tested

• Doxorubicin (doxorubicin) — full drug profile →

Conditions studied

• Glioblastoma (GBM) — all drugs for Glioblastoma (GBM) →
• DIPG — all drugs for DIPG →
• Brainstem Glioma, Pediatric — all drugs for Brainstem Glioma, Pediatric →
• Diffuse Spinal Glioma — all drugs for Diffuse Spinal Glioma →

Sponsor

Meyer Children's Hospital IRCCS

Who can join

Adults 3 to 30, any sex, with Glioblastoma (GBM) or DIPG. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Time to early discontinuation of the study drug (doxorubicin)
  Time frame: 6 months
• Number of participants with treatment-related serious adverse events (SAE) as assessed by CTCAE v4.0
  Time frame: 32 months
  Number of patients with SAE and SAE leading to withdrawal from the study
• Number of patients who died for SAE as assessed by CTCAE v4.0
  Time frame: 32 months
  Mortality due to adverse events
• Number of patients who undergone to withdrawal of doxorubicin
  Time frame: 6 months
  Rate of early suspension of the study drug (doxorubicin)

Sponsor's own description

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).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Therapeutic strategies for diffuse midline glioma from high-throughput combination drug screening.
   Lin GL, Wilson KM, Ceribelli M, Stanton BZ, et al · · 2019 · cited 158× · PMID 31748226 · DOI 10.1126/scitranslmed.aaw0064
2. Nanomedicine and macroscale materials in immuno-oncology.
   Sun Q, Barz M, De Geest BG, Diken M, et al · · 2019 · cited 95× · PMID 30465669 · DOI 10.1039/c8cs00473k
3. Role of Radiation Therapy in the Management of Diffuse Intrinsic Pontine Glioma: A Systematic Review.
   Gallitto M, Lazarev S, Wasserman I, Stafford JM, et al · · 2019 · cited 73× · PMID 31360809 · DOI 10.1016/j.adro.2019.03.009
4. Nanotechnology Meets Oncology: Nanomaterials in Brain Cancer Research, Diagnosis and Therapy.
   Zottel A, Videtič Paska A, Jovčevska I. · · 2019 · cited 70× · PMID 31096609 · DOI 10.3390/ma12101588
5. Next Generation Sequencing and Machine Learning Technologies Are Painting the Epigenetic Portrait of Glioblastoma.
   Jovčevska I. · · 2020 · cited 28× · PMID 32500035 · DOI 10.3389/fonc.2020.00798
6. Local delivery of doxorubicin prodrug via lipid nanocapsule-based hydrogel for the treatment of glioblastoma.
   Wang M, Bergès R, Malfanti A, Préat V, et al · · 2024 · cited 16× · PMID 37889402 · DOI 10.1007/s13346-023-01456-y
7. Topoisomerase II Poisons for Glioblastoma; Existing Challenges and Opportunities to Personalize Therapy.
   Mehta A, Awah CU, Sonabend AM. · · 2018 · cited 14× · PMID 29988316 · DOI 10.3389/fneur.2018.00459
8. Introducing HDAC-Targeting Radiopharmaceuticals for Glioblastoma Imaging and Therapy.
   Everix L, Seane EN, Ebenhan T, Goethals I, et al · · 2023 · cited 11× · PMID 37259375 · DOI 10.3390/ph16020227