GliomaPhase 2NCT03741244
TMZ Plus Apatinib in Newly Diagnosed High-grade Glioma：RCT
A Phase 2 study testing apatinib and Temozolomide in people with Glioma, run by The Second Hospital of Hebei Medical University at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioma
- What is being tested?
- apatinib and Temozolomide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 211 participants
- Where
- 1 siteChina
- Study dates
- 6 May 2019to Feb 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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;
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- 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
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
the Second Hospital of Hebei Medical University
Shijiazhuang
xiaoying xue
About this study
Official title: A Randomized Controlled Clinical Trial of Temozolomide Plus Apatinib in Newly Diagnosed High-grade Glioma
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.
Read the detailed 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. 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 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.
- Conditions
- Glioma
- Being tested
- apatinib, Temozolomide
- Keywords
- glioma, Apatinib, VEGFR-2, temozolomide
- Medical subject headings
- Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
apatinibDrug
Also called antiangiogenic targeted 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
TemozolomideDrug
Also called TMZ
Temozolomide，alkylating agent， is the standard first-line chemotherapy of glioma.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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). Receives: Drug: Temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival（PFS）
Record the time from the start of enrollment to the progression of disease or death.
Measured: 1 year
Secondary outcomes (2)
rate of 2-year Overall survival（OS）
Record the time from the start of enrollment to death for any reason.
Measured: 2 years
Incidence of Treatment-Emergent Adverse Events
Record the toxicity reactions of hematology, digestive tract, skin and cardiovascular system every month,Adverse reactions were classified As "WHO classification criteria for common toxic reactions of anticancer drugs".
Measured: every month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Nov 2018
- Study start6 May 2019
- Primary completionOct 2022 (estimated)
- Study completionFeb 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GliomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 211 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Second Hospital of Hebei Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Xue Xiaoying, The Second Hospital of Hebei Medical University
- Investigators
- Xiao-Ying Xue, Xue, Principal investigator, The Second Hospital of Hebei Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03741244
- Sponsor's protocol ID
- APAglio
- Status last verified
- Jan 2019
- First submitted
- 13 Nov 2018
- Last updated
- 23 Jul 2019
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Clinical Trial of Temozolomide Plus Apatinib in Newly Diagnosed High-grade Glioma
- ClinicalTrials.gov ID
- NCT03741244
- Acronym / sponsor ID
- APAglio
- Conditions
- Glioma
- Keywords
- glioma, Apatinib, VEGFR-2, temozolomide
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 211 participants (estimated)
- Lead sponsor
- The Second Hospital of Hebei Medical UniversityUniversity, hospital or other
- Study start
- 6 May 2019 (actual)
- Primary completion
- Oct 2022 (estimated)
- Study completion
- Feb 2023 (estimated)
- First posted
- 14 Nov 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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. 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 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Temozolomide and apatinib | Experimental | Drug: apatinib, Drug: TemozolomidePatients 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. |
| Temozolomide | Active comparator | Drug: TemozolomidePatients 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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) ;
Key exclusion criteria (13 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| apatinibAlso: antiangiogenic targeted drugApatinib 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 | Drug | Temozolomide and apatinib |
| TemozolomideAlso: TMZTemozolomide，alkylating agent， is the standard first-line chemotherapy of glioma. | Drug | Temozolomide, Temozolomide and apatinib |
Primary outcome
Progression Free Survival（PFS）
Time frame: 1 year
Record the time from the start of enrollment to the progression of disease or death.
2 secondary outcomes
rate of 2-year Overall survival（OS）
Time frame: 2 years
Incidence of Treatment-Emergent Adverse Events
Time frame: every month
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Xiao-Ying Xue, Xue principal investigator
The Second Hospital of Hebei Medical University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing apatinib and Temozolomide in people with Glioma, run by The Second Hospital of Hebei Medical University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 23 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Xiao-Ying Xue, Professor (+8615803210636, xxy0636@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression Free Survival（PFS） (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jul 2019.