Clinical Study on the Treatment of Recurrent Glioblastoma With Anlotinib

Study Overview
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Brief Summary
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Anlotinib is a novel small molecule multi-target tyrosine kinase inhibitor that can inhibit tumor angiogenesis and inhibit tumor cell growth. We performed second-generation gene sequencing on pathological specimens and cerebrospinal fluid of patients with recurrent glioblastoma.If patients have a genetic mutation （VEGFR，Kit，PDGFR，FGFR）and meet other eligibility criteria, they will be treated with antroinib. The initial observation targets were progression-free survival and adverse reactions. The secondary objective was overal survival.

Detailed Description
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INCLUSION CRITERIA: Histologically confirmed World Health Organization (WHO) Grade IV glioblastoma.; Radiographic evidence of tumour progression or recurrence; The second-generation gene sequencing on pathological specimens and cerebrospinal fluid show at least one genetic mutation of the four genes (VEGFR，Kit，PDGFR，FGFR); ≥ 18 years of age; Karnofsky performance status (KPS) ≥ 70; Corticosteroid dose must be stable or decreasing for at least 5 days prior to the scan. a new baseline scan is required 1.7 Measurable disease as per Response Assessment in Neuro-Oncology (RANO) criteria; Estimated survival of at least 3 months; signed informed consent form; Hgb > 9 gm; absolute neutrophil count (ANC) > 1500/μl; platelets > 100,000; Creatinine < 1.5 times the upper limit of laboratory normal value; Bilirubin < 2 times the upper limit of laboratory normal value; serum glutamate pyruvate transaminase (SGPT) or serum glutamate oxaloacetate transaminase (SGOT) < 3 times the upper limit of laboratory normal value; EXCLUSION CRITERIA: Exclusion Criteria: Subjects with newly diagnosed GBM Pregnant women or nursing mothers cannot participate in the study. Women of childbearing age must have a negative pregnancy test within 72 hours prior to study entry. Women of childbearing potential must practice medically approved contraceptive precautions; Abnormal hematological results at inclusion with: Neutrophils < 1,500/mm3; Blood-platelets < 100,000/mm3 Severe or chronic renal insufficiency (creatinine clearance ≤ 30 ml/min); Patient unable to follow procedures, visits, examinations described in the study; Any usual formal indication against imaging examinations (important claustrophobia, pacemaker);

Official Title
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Phase II Clinical Trials on Anlotinib for the Treatment of Recurrent Glioblastoma.

Conditions
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Recurrent Glioblastoma

Intervention / Treatment
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* Drug: Anlotinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed World Health Organization (WHO) Grade IV glioblastoma.; Radiographic evidence of tumour progression or recurrence; The second-generation gene sequencing on pathological specimens and cerebrospinal fluid show at least one genetic mutation of the four genes (VEGFR，Kit，PDGFR，FGFR); ≥ 18 years of age; Karnofsky performance status (KPS) ≥ 70; Corticosteroid dose must be stable or decreasing for at least 5 days prior to the scan. a new baseline scan is required 1.7 Measurable disease as per Response Assessment in Neuro-Oncology (RANO) criteria; Estimated survival of at least 3 months; signed informed consent form; Hgb > 9 gm; absolute neutrophil count (ANC) > 1500/μl; platelets > 100,000; Creatinine < 1.5 times the upper limit of laboratory normal value; Bilirubin < 2 times the upper limit of laboratory normal value; serum glutamate pyruvate transaminase (SGPT) or serum glutamate oxaloacetate transaminase (SGOT) < 3 times the upper limit of laboratory normal value; Exclusion Criteria: Subjects with newly diagnosed GBM Pregnant women or nursing mothers cannot participate in the study. Women of childbearing age must have a negative pregnancy test within 72 hours prior to study entry. Women of childbearing potential must practice medically approved contraceptive precautions; Abnormal hematological results at inclusion with: Neutrophils < 1,500/mm3; Blood-platelets < 100,000/mm3 Severe or chronic renal insufficiency (creatinine clearance ≤ 30 ml/min); Patient unable to follow procedures, visits, examinations described in the study; Any usual formal indication against imaging examinations (important claustrophobia, pacemaker);

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: one-armed controlled clinical trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: anlotinib<br>12 mg daily from day 1 to 14 of a 21-day cycle | Drug: Anlotinib<br>* Anlotinib is a multitarget receptor tyrosine kinase inhibitor which inhibits vascular endothelial growth factor receptor (VEGFR) 1-3, fibroblast growth factor receptor (FGFR) 1-4, platelet-derived growth factor receptors (PDGFR) α/β, c-Kit, and Met.<br>* Other names: Fu Ke Wei;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progress free survival (PFS) | PFS defined as the time from first dose of study treatment until the first date of either objective disease progression or death due to any cause. | each 42 days up to PD or death(up to 24 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS is defined as the time until death due to any cause. | From randomization until death (up to 24 months) | 
| Objective Response Rate (ORR) | ORR is defined as the percentage of subjects with evidence of a confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1.prior to progression or any further therapy. | each 42 days up to intolerance the toxicity or PD (up to 24 months) | 
| Disease Control Rate (DCR) | Defined as the proportion of patients with a documented complete response, partial response, and stable disease (CR + PR + SD) based on RECIST 1.1. | each 42 days up to intolerance the toxicity or PD (up to 24 months) | 
| Quality of Life score (QoL) | use EORTC QLQ-C30(version 3) questionnaire to evaluate the quality of life. | each 42 days up to intolerance the toxicity or PD (up to 24 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anlotinib Recurrent Glioblastoma