Overview

TMZ Plus Apatinib in Newly Diagnosed High-grade Glioma：RCT

Status:
Recruiting

Trial end date:
2023-02-01

Target enrollment:
0

Participant gender:
All

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. AVAglio＆RTOG 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 glioma，and 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.

Phase:

Phase 2

Accepts Healthy Volunteers?

Details

Lead Sponsor:

The Second Hospital of Hebei Medical University

Treatments:

Angiogenesis Inhibitors
Apatinib
Dacarbazine
Temozolomide

Criteria

Inclusion Criteria:

1. Age ≥ 18 years;

2. Pathological or cytological diagnosis of glioma (WHO Ⅲ or Ⅳ);

3. KPS score ≥ 60;

4. The expected survival period is ≥ 3 months;

5. 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) ;

6. Normal liver and kidney function.

Exclusion Criteria:

1. Pregnant or lactating women;

2. Second primary malignancy;

3. Severe lung infection;

4. with high blood pressure although treated with medication;

5. Patients with myocardial ischemia or myocardial infarction, arrhythmia (including QT
interval > 440 ms) or grade II cardiac insufficiency;

6. Conditions that significantly affect oral drug absorption, such as inability to
swallow, chronic diarrhea, and intestinal obstruction;

7. Abnormal coagulation function （INR>1.5 or PT>ULN+4s or APTT >1.5 ULN);

8. Haemorrhagic tendencies or being treated with thrombolysis or anticoagulation;

9. ≥CTCAE level 2 Pulmonary hemorrhage or ≥CTCAE level 3 other organ hemorrhage occurred
within 4 weeks before the first administration of the study drug;

10. Arteriovenous thrombosis in 6 months prior to first administration, Such as
cerebrovascular accident (including temporary ischemic attack), deep vein thrombosis
and pulmonary embolism;

11. Small doses of warfarin(1mg/day) or heparin(80-100mg/day) is permitted unless INR
≤1.5;

12. Serious heart, lung and bone marrow impairment;

13. History of severe hypertension or cerebral hemorrhage