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

  • STATUS
    Recruiting
  • End date
    Nov 30, 2023
  • participants needed
    109
  • sponsor
    Beijing Sanbo Brain Hospital
Updated on 27 January 2021

Summary

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.

Details
Condition Glioblastoma, Recurrent, Lower Grade Glioma, Recurrent, Glioblastoma, Recurrent, Lower Grade Glioma, Recurrent, Glioblastoma, Recurrent, Lower Grade Glioma, Recurrent
Treatment recombinant human endostatin,temozolomide,irinotecan
Clinical Study IdentifierNCT04267978
SponsorBeijing Sanbo Brain Hospital
Last Modified on27 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Age 18 and 70
Histopathologically-confirmed, supratentorial GBM or lower-grade gliomas (such as oligodendroglioma, astrocytoma, oligoastrocytoma, anaplastic astrocytoma, anaplastic oligodendroglioma or anaplastic oligoastrocytoma)
Recurrence is pathologically confirmed by another biopsy or surgery, which should have been completed at least 2 weeks before enrollment, or confirmed by the MRI according to RANO criteria, at least one bi-dimensionally measurable contrast-enhancing target lesion, with one diameter at least 10 mm, visible on two or more axial slices 5mm apart
Received standard chemoradiotherapy and at least one cycle of chemotherapy after primary diagnosis
The time intervals between the last radiotherapy and enrollment are at least 3 months
The interval form the last chemotherapy to the study enrollment was at least one interval of chemotherapy with recover from the related toxic effects (except for hair loss and pigmentation)
Karnofsky Performance Status 60
If the patient is on glucocorticoid therapy, hormone dosage should be stable or decreased at least 5 days before baseline MRI
If the patient is receiving enzyme-inducing antiepileptic drugs (EIAEDs), the drugs should be replaced with non-EIAEDs for at least 1 weeks away from enrollment
Estimated survival of at least 12 weeks
Participants must have adequate organ function as defined by the following criteria (within 7 days before treatment)
Hematology (No transfusion within 14 days)
Hemoglobin(HB)90g/L
Absolute neutrophil count (ANC)1.5109/L
Platelet (PLT)80109/L
Chemistry
Serum bilirubin 1.5upper limit of normal (ULN)
ALT and AST2.5ULN
Serum creatinine 1.5ULN or creatinine clearance rate(CCr)60ml/min
ECG: heart rate in the normal range (55-100beats/min), normal or slightly prolonged QT interval (QTc<480ms), normal or low T wave, normal or non-specific ST segment changes
Both men and women at the gestational age must agree to take adequate contraceptive measures throughout the study period
Participants volunteered to participate in the study and signed an informed consent form (ICF)

Exclusion Criteria

MRI examination is not available (such as pacemaker, metal denture)
Receiving any other investigational agent
History of allergic reactions attributed to compounds of similar chemical or biologic composition to the drugs used in this study
Patients who have received organ transplants
Patients with HIV or Treponema pallidum infection
Severe heart disease; ECG shows T wave inversion or elevation or ST segment specific changes
Having factors that affect oral drug absorption, such as vomiting, diarrhea and intestinal obstruction
There were clinically significant bleeding symptoms or clear bleeding tendency in the first 3 months before enrollment, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, gastrointestinal perforation, baseline fecal occult blood ++ and above, intracranial or intracranial hemorrhage, or vasculitis
Arteriovenous thrombosis events occurred within 6 months before enrollment, such as cerebrovascular accidents (including temporary ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism, etc
Having bleeding disorder and are being treated with thrombolytic or anticoagulant drugs
Other conditions considered inappropriate by the researcher for inclusion
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