NCT04267978

Study of Recombinant Human Endostatin Combined with Temozolomide and Irinotecan in Recurrent Gliomas

Recruiting now Phase 2 Last updated 15 October 2024

What this trial tests

Phase 2 trial testing recombinant human endostatin,temozolomide,irinotecan in Glioblastoma, Recurrent in 109 participants. Currently enrolling.

Timeline

13 February 2020

Primary endpoint
31 December 2025

31 December 2025

Quick facts

Lead sponsor	Beijing Sanbo Brain Hospital
Phase	Phase 2
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	109
Start date	13 February 2020
Primary completion	31 December 2025
Estimated completion	31 December 2025
Sites	1 location across China

Drugs / interventions tested

• recombinant human endostatin,temozolomide,irinotecan — full drug profile →

Conditions studied

• Glioblastoma, Recurrent — all drugs for Glioblastoma, Recurrent →
• Lower Grade Glioma, Recurrent — all drugs for Lower Grade Glioma, Recurrent →

Sponsor

Beijing Sanbo Brain Hospital

Who can join

Adults 18 to 70, any sex, with Glioblastoma, Recurrent or Lower Grade Glioma, Recurrent. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Almost all gliomas relapse. After temozolomide rechallenge or combination with irinotecan, the progression-free survival rate at 6 months (PFS-6%) of recurrent glioblastoma was about 21%. After treatment with irinotecan-based chemotherapy regimen, the PFS-6% of recurrent lower-grade gliomas was 40%. The optimal chemotherapeutics of recurrent gliomas has yet to be determined.

Anti-angiogenesis is a promising therapeutic strategy. Vascular endothelial growth factor-A (VEGF) is the primary driver of angiogenesis in tumors. Bevacizumab, a humanized monoclonal antibody directed against VEGF, is the prototypical anti-angiogenic drug and received accelerated approval of the United States Food and Drug Administration (FDA) for the treatment of recurrent glioblastoma. Bevacizumab inproved the PFS-6% (36%), but had no effect on the overall survival (OS) (9.2 months). Moreover, the effects of bevacizumab are transient and most patients' tumors progress just after a median time of 3-5 months. Recombinant human endostatin (rh-ES) is an endogenous broad-spectrum angiogenesis inhibitor that has been shown to significantly improve therapeutic efficacy when combining with conventional chemotherapy agents in non-small-cell lung cancer, breast cancer and melanoma.

In our previous study, we retrospectively analyzed the effect and toxicity of rh-ES when combined with temozolomide and irinotecan on adult recurrent disseminated glioblastoma. After combined treatment, PFS-6% was 23.3%; the median PFS and OS were 3.2 and 6.9 months, respectively, which were promising compared with that in other studies. Once patients get radiographic remission in a short time (4 months), they may get a long PFS.The combined regimen did not reduce the sensitivity of tumor to bevacizumab. After tumor progression from the combined chemotherapy, bevacizumab usage could help to prolong the survival time (5.1 months versus 2.4 months). Moreover, the toxicities of the combination therapy in this study were manageable.

On the basis of prior clinical experience, we carry out this prospective trial to confirm the efficacy and safety of the combination of rh-ES, temozolomide and irinotecan in patients with recurrent gliomas.

Publications & conference data

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

1. Glioblastoma multiforme (GBM): An overview of current therapies and mechanisms of resistance.
   Wu W, Klockow JL, Zhang M, Lafortune F, et al · · 2021 · cited 532× · PMID 34302977 · DOI 10.1016/j.phrs.2021.105780
2. A Systematic Review of Glioblastoma-Targeted Therapies in Phases II, III, IV Clinical Trials.
   Cruz Da Silva E, Mercier MC, Etienne-Selloum N, Dontenwill M, et al · · 2021 · cited 99× · PMID 33918704 · DOI 10.3390/cancers13081795
3. Understanding the Role of Endothelial Cells in Glioblastoma: Mechanisms and Novel Treatments.
   Hovis G, Chandra N, Kejriwal N, Hsieh KJ, et al · · 2024 · cited 11× · PMID 38892305 · DOI 10.3390/ijms25116118
4. Investigational treatment strategies in glioblastoma: progress made and barriers to success.
   Nelson TA, Dietrich J. · · 2023 · cited 11× · PMID 37796104 · DOI 10.1080/13543784.2023.2267982
5. Current evidence and challenges of multitarget anti-angiogenic agents for glioblastoma: Results from clinical trials.
   Liu X, Chen Z, Wang X, Yan P, et al · · 2025 · cited 1× · PMID 41050932 · DOI 10.1016/j.isci.2025.113521