Actively Recruiting

Phase 2
Age: 18Years - 70Years
All Genders
NCT04267978

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

Led by Beijing Sanbo Brain Hospital · Updated on 2024-10-15

109

Participants Needed

1

Research Sites

306 weeks

Total Duration

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AI-Summary

What this Trial Is About

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.

CONDITIONS

Official Title

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

Who Can Participate

Age: 18Years - 70Years
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Age between 18 and 70 years
  • Histologically confirmed supratentorial glioblastoma or lower-grade gliomas
  • Recurrence confirmed by biopsy or MRI with measurable tumor lesion at least 10 mm in size
  • Prior standard chemoradiotherapy and at least one chemotherapy cycle after initial diagnosis
  • At least 3 months since last radiotherapy
  • At least one chemotherapy cycle interval since last chemotherapy with recovery from toxic effects
  • Karnofsky Performance Status of 60 or higher
  • Stable or decreased glucocorticoid hormone dose for at least 5 days before baseline MRI
  • Replacement of enzyme-inducing antiepileptic drugs with non-enzyme-inducing ones for at least 1 week before enrollment
  • Estimated survival of at least 12 weeks
  • Adequate organ function within 7 days before treatment including hemoglobin 6 g/L, neutrophil count 1.5 x 10�9/L, platelet count 8 x 10�9/L, serum bilirubin 1.5 times upper limit, ALT and AST 2.5 times upper limit, creatinine 1.5 times upper limit or creatinine clearance 60 ml/min, and normal ECG
  • Both men and women of childbearing potential agree to use effective contraception during the study
  • Voluntary participation with signed informed consent
Not Eligible

You will not qualify if you...

  • MRI examination not possible (e.g., pacemaker, metal dentures)
  • Receiving other investigational agents
  • History of allergic reactions to drugs similar to those used in this study
  • History of organ transplant
  • Infection with HIV or Treponema pallidum
  • Severe heart disease or abnormal ECG including T wave inversion or ST segment changes
  • Conditions affecting oral drug absorption such as vomiting, diarrhea, or intestinal obstruction
  • Significant bleeding or bleeding tendency within 3 months before enrollment
  • Arteriovenous thrombosis events within 6 months before enrollment
  • Bleeding disorders treated with thrombolytic or anticoagulant drugs
  • Other conditions deemed inappropriate by the investigator for participation

AI-Screening

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Trial Site Locations

Total: 1 location

1

Beijing Sanbo Brain Hospital

Beijing, China

Actively Recruiting

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Research Team

J

Jun-ping Zhang

CONTACT

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NON_RANDOMIZED

Model

PARALLEL

Primary Purpose

TREATMENT

Number of Arms

2

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