Apatinib in Recurrent or Refractory Intracranial Central Nervous System Malignant Tumors

Study Overview
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Brief Summary
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The patient was given a daily dose of apatinib 500mg (or based on weight). Individualized chemotherapy regimens were given based on molecular expression and prior chemotherapy.

Detailed Description
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The patient was given a daily dose of apatinib 500mg (or based on weight). Individualized chemotherapy regimens were given based on molecular expression and prior chemotherapy. Brain MRI+MRS was examined every 3 months; Blood routine, urine routine and liver and kidney function were examined once a week.

Official Title
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Efficacy and Safety of Apatinib Combined With Dose-dense Temozolomide in Recurrent Glioblastoma

Conditions
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Efficacy and Safety

Intervention / Treatment
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* Drug: apatinib
* Drug: temodar


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: (1) 18 years < the age of patients > 70 years. (2) Karnofsky performance scale (KPS) ≥ 60. (2) Histologically confirmed diagnosis of GBM World Health Organization [WHO] Grade IV. (3) They were required to have measurable or evaluable disease by magnetic resonance imaging (MRI) confirmation and a minimum life expectancy of 8 weeks. (4) Definition of relapse: all patients must have progressive disease on MRI defined by Response Assessment in Neuro-Oncology (RANO) criteria after the standard Stupp protocol. The time interval for the start of treatment was at least 12 weeks from prior radiotherapy unless there was either histopathologic confirmation of recurrent tumor or new contrast enhancement on MRI outside of the radiotherapy treatment field. (5) Adequate bone marrow function (leukocyte count ≥ 4000/μL, neutrophil count ≥1500/µL, platelet count ≥100 000/µL, hemoglobin ≥8.0g/dL), adequate renal function (serum creatinine ≤ 150μmol/L, 24 hours urine protein ≤3.4g), and liver function (total bilirubin ≤34μmol/L and aspartate and alanine aminotransferase ≤120U/L). Exclusion Criteria: (1) extracranial metastatic disease, (2) Gliadel wafer treatment, (3) severe cardiopulmonary insufficiency, (4) status epilepticus, (5) pregnancy, (6) gastrointestinal bleeding, (7) uncontrolled blood pressure with medication (>140/90 mm Hg), (8) swallowing difficulties. (9) HIV positivity with a combination antiretroviral therapy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: single arm
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: apatinib 500mg<br> | Drug: apatinib<br>* The patient was given a daily dose of apatinib 500mg (or based on weight). For adult, the dose of apatinib was prescribed with 425 mg or 500 mg per day and four weeks for a cycle. The dosage was modified to 250 mg if patients experienced ≧grade 2 hematologic adverse events, hand and foot syndrome, proteinuria, fecal ocular blood, or grade 3/4 hypertension, or other grade 3/4 adverse events. Apatinib was administrated until disease progression, unacceptable toxicity or death.<br>Drug: temodar<br>* dose-dense temozolomide (100 mg/m2 , 7 days on with 7 days off ) , 28d<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response to treatment | Response were evaluatedevery 1-3 months with Response Evaluation Criteria in Solid Tumors version 1.0 (RECIST 1.0) usingdynamic contrast enhancement magnetic resonance imaging (MRI) or computed tomography (CT). Complete response (CR) was defined as complete disappearance of target lesions and maintaining ≥ 4 weeks; partial response (PR): ≥ 30% reduction in maximum diameterof tumor and keepingstable ≥ 4 weeks; progressive disease (PD):>20% increase in bidimensionalmeasurements of the lesions, or emerging one or more newlesions; stable disease (SD): criteria for CR, PR and PDnot met.PFS was defined as the initial treatment to the disease progression or the date of death. | up to 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median non-progress survival (PFS) | Median non-progress survival (PFS) | up to 12 months |