TMZ Plus Apatinib in Newly Diagnosed High-grade Glioma RCT

  • STATUS
    Recruiting
  • End date
    Feb 22, 2023
  • participants needed
    211
  • sponsor
    The Second Hospital of Hebei Medical University
Updated on 22 January 2021
blood transfusion
bevacizumab
temozolomide
malignant glioma
brain tumor
recurrent glioma

Summary

Glioma is the most common primary malignant Brain Tumor. Although the traditional treatment (surgery, radiotherapy and chemotherapy) has been actively carried out, the curative effect of High grade glioma (HGG) is still poor.On the basis of a lot of exploration, the union medication has become a hot spot. Malignant glioma has obvious neovascularization and inhibiting angiogenesis can inhibit tumor proliferation and invasion.Studies have found that inhibiting VEGFR-2 can can reduce neovascularization and inhibit tumor growth. NCCN clinical practice guidelines recommend bevacizumab(BEV) for the treatment of recurrent malignant gliomas. AVAglioRTOG 0825 subgroup analysis showed that TMZ combined with antiangiogenic drugs may have advantages in the first-line treatment of patients with IDH1 wild-type high grade glioma.However, some studies have shown that bevacizumab can lead to rapid deterioration due to hypoxia or phenotypic changes. So it is urgent to find new antiangiogenic drugs. Apatinib is an oral small molecule antiangiogenic targeted drug. Apatinib plus temozolomide has been shown to be effective and tolerable in recurrent glioma. So the investigators aimed to evaluate the efficacy and safety of temozolomide combined with apatinib in the new diagnosis of high-grade gliomaand to explore the new first-line treatment of HGG, especially to TMZ insensitivity patients(MGMT gene promoter unmethylated) and poor prognosis (IDH1 wild type) population. And Find out the benefit groups of the two drugs.

Description

Glioma is the most common primary malignant Brain Tumor.High grade glioma (HGG) has the characteristics of high morbidity, high relapse and high incidence of causing disability.Despite the progress in the combined treatment of surgery, radiotherapy and chemotherapy, the 2-year survival rate and 2-year non-progression survival rate were only 27.2% and 11.2%, respectively.

TMZ is the standard first-line chemotherapy, which can prolong the overall survival time and the progression-free survival time. Although TMZ has achieved satisfactory therapeutic effect since its application, the overall response rate of TMZ alone is still low which related to the methylation level of MGMT promoter.

On the basis of a lot of exploration, the union medication has become a hot spot. Malignant glioma has obvious neovascularization and inhibiting angiogenesis can inhibit tumor proliferation and invasion.

In recent years, antiangiogenic drugs have become a new treatment for malignant glioma. In recent years, studies have found that inhibiting VEGFR-2 can improve the sensitivity of glioma to TMZ chemotherapy. NCCN clinical practice guidelines recommend bevacizumab(BEV) for the treatment of recurrent malignant gliomas. Numerous clinical trials have studied the role of bevacizumab on glioma, and proved that bevacizumab can effectively prolong PFS without significant benefit to OS. AVAglioRTOG 0825 subgroup analysis showed that TMZ combined with antiangiogenic drugs may have advantages in the first-line treatment of patients with IDH1 wild-type high grade glioma.

However, some studies have shown that bevacizumab can lead to rapid deterioration due to hypoxia or phenotypic changes. So it is urgent to find new antiangiogenic drugs. Apatinib is an oral small molecule antiangiogenic targeted drug developed in China. As a specific vegfr-2 receptor inhibitor, apatinib plus temozolomide has been shown to be effective and tolerable in patients with recurrent glioma, but high-level evidence is still lacking. So the investigators conducted this clinical trial aimed to explore the new first-line treatment of high-grade glioma. The combination of TMZ and apatinib may have synergistic effect especially to TMZ insensitivity patients(MGMT gene promoter unmethylated) and poor prognosis (IDH1 wild type) population, as the high-level evidence is imminent.

From the perspective of molecular mechanism, A large number of studies have shown that vascular microenvironment closely related to glioma stem cell-like cells (GSLCs) and GSLCs can stimulate the proliferation by releasing VEGF to promote angiogenesis.. There was a correlation between the expression of vegfr-2 and CD133, a molecular biomarker of cancer stem cells. Therefore, CD133 may be an indirect target for the treatment of apatinib, and the therapeutic effect of apatinib may be related to the expression of CD133, not only vegfr-2. Monitoring the expression of CD133 can reflect the content of glioma stem cells on the one hand and indirectly reflect the therapeutic effect of vegfr-2 blocker apatinib on the other hand.

Details
Condition Glioma, Gliomas, glial tumor
Treatment Temozolomide, apatinib
Clinical Study IdentifierNCT03741244
SponsorThe Second Hospital of Hebei Medical University
Last Modified on22 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Age 18 years
Pathological or cytological diagnosis of glioma (WHO or )
KPS score 60
The expected survival period is 3 months
Blood routine examination is basically normal: a. HB 90 G /L; b. the ANC 1.5 x 10^9/L; c. PLT 80 x 10^9/L (without blood transfusion within 2 weeks, or G-CSF and other hematopoietic stimulator correction)
Normal liver and kidney function

Exclusion Criteria

Pregnant or lactating women
Second primary malignancy
Severe lung infection
with high blood pressure although treated with medication
Patients with myocardial ischemia or myocardial infarction, arrhythmia (including QT interval > 440 ms) or grade II cardiac insufficiency
Conditions that significantly affect oral drug absorption, such as inability to swallow, chronic diarrhea, and intestinal obstruction
Abnormal coagulation function INR>1.5 or PT>ULN+4s or APTT >1.5 ULN)
Haemorrhagic tendencies or being treated with thrombolysis or anticoagulation
CTCAE level 2 Pulmonary hemorrhage or CTCAE level 3 other organ hemorrhage occurred within 4 weeks before the first administration of the study drug
Arteriovenous thrombosis in 6 months prior to first administration, Such as cerebrovascular accident (including temporary ischemic attack), deep vein thrombosis and pulmonary embolism
Small doses of warfarin(1mg/day) or heparin(80-100mg/day) is permitted unless INR 1.5
Serious heart, lung and bone marrow impairment
History of severe hypertension or cerebral hemorrhage
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