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

NCT03741244 | Unknown Phase 2

• 1 other identifier: APAglio
• Study Type: interventional
• Target: 211
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Glioma

Keywords

glioma; Apatinib; VEGFR-2; temozolomide

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival（PFS）

  Record the time from the start of enrollment to the progression of disease or death.

  1 year

Secondary Outcomes (2)

• rate of 2-year Overall survival（OS）

  2 years

• Incidence of Treatment-Emergent Adverse Events

  every month

Study Arms (2)

Temozolomide and apatinib

EXPERIMENTAL

Patients have treated with postoperative concurrent chemoradiation. Then Temozolomide (150mg/m2/d d1-5 in the first cycle, followed by 200mg/m2/d d1-5 q28d) + apatinib (500mg/d QD). After 6 cycles,apatinib single drug maintained until progress.

Drug: apatinib; Drug: Temozolomide

Temozolomide

ACTIVE COMPARATOR

Patients were treated with postoperative concurrent chemoradiation.Then Temozolomide alone chemotherapy 6 cycles(first cycle 150mg/m2/d d1-5, later 200mg/m2/d d1-5 q28d).

Drug: Temozolomide

Interventions

apatinib DRUG

Apatinib is an oral small molecule antiangiogenic targeted drug developed in China. More and more studies found that antiangiogenic drugs have outstanding performance in treating glioma. From the perspective of clinical and molecular mechanism, the combination of Temozolomide and apatinib may have synergistic effect especially to TMZ insensitivity patients(MGMT gene promoter unmethylated) and poor prognosis (IDH1 wild type) population

Also known as: antiangiogenic targeted drug

Temozolomide and apatinib

Temozolomide DRUG

Temozolomide，alkylating agent， is the standard first-line chemotherapy of glioma.

Also known as: TMZ

Temozolomide; Temozolomide and apatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years;
• Pathological or cytological diagnosis of glioma (WHO Ⅲ or Ⅳ);
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• The Second Hospital of Hebei Medical University: lead

Study Sites (1)

the Second Hospital of Hebei Medical University

Shijiazhuang, China

RECRUITING

MeSH Terms

Conditions

Glioma

Interventions

apatinib; Temozolomide

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Xiao-Ying Xue, Xue

  The Second Hospital of Hebei Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xiao-Ying Xue, Professor

CONTACT

+8615803210636; xxy0636@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Radiotherapy

Study Record Dates

• First Submitted: November 13, 2018
• First Posted: November 14, 2018
• Study Start: May 6, 2019
• Primary Completion: October 1, 2022
• Study Completion: February 1, 2023
• Last Updated: July 23, 2019

Record last verified: 2019-01

Locations

CN (1)