Hypofractionated Stereotactic Radiotherapy With Anlotinib in Patients With Recurrent High-Grade Gliomas

Study Overview
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Brief Summary
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A Phase II Study of Hypofractionated Stereotactic Radiotherapy (HSRT) With Anlotinib in Patients With Recurrent High-Grade Glioma. The primary endpoint is overall survival after radiotherapy. Secondary endpoints included progress-free survival, objective response rate, cognitive function, quality of life, toxicity.

Detailed Description
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Original histopathologically proven diagnosis World Health Organization (WHO) Grade 3/4 glioma patients who underwent surgery, chemoradiotherapy and adjuvant chemotherapy (Stupp Protocol). Recurrence based on Response Assessment in Neuro-Oncology (RANO) criteria and/or histopathology. Intervention included CyberKnife hypofractionated stereotactic radiotherapy (25Gy/5fx) with Anlotinib once daily (12mg/d) on days 1-14 of a 21-day cycle.

Official Title
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A Phase II Study of Hypofractionated Stereotactic Radiotherapy Combined With Anlotinib in Patients With Recurrent High-Grade Glioma

Conditions
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Malignant Glioma

Intervention / Treatment
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* Radiation: Hypofractionated Stereotactic Radiotherapy
* Drug: Anlotinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-70 years of age; Karnofsky performance status (KPS) ≥ 60; Original histopathologically proven diagnosis World Health Organization (WHO) Grade 3/4 glioma; Underwent surgery, chemoradiotherapy and adjuvant chemotherapy (Stupp Protocol) after initial diagnosis, recurrent based on the Response Assessment in Neuro-Oncology (RANO) criteria and/or histopathologically proven; Measurable disease; Estimated survival of at least 3 months; 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; Signed informed consent form; Agreed to participate the follow-up. Exclusion Criteria: Prior invasive malignancy unless disease free; Received re-irradiation; More than 3 relapses or evidence of subtentorial recurrent disease or tumor greater than 6 cm in maximum diameter; Prior therapy with an inhibitor of vascular endothelial growth factor (VEGF) or VEGFR; Pregnancy or or nursing mothers; Participated in other trials after diagnosis of recurrent; Influence factors toward oral medications; Patients with CTCAE5.0 grade 3+ bleeding; Suffering from severe cardiovascular disease: myocardial ischemia or myocardial infarction above grade II, poorly controlled arrhythmias (including men with QTc interval ≥ 450 ms, women ≥ 470 ms); according to NYHA criteria, grades III to IV Insufficient function, or cardiac color Doppler ultrasound examination indicates left ventricular ejection fraction (LVEF) <50%; Long-term unhealed wounds or fractures; History of organ transplantation; Serious diseases that endanger patients' safety or affect patients' completion of research,according to the researchers' judgment.

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HSRT With Anlotinib<br>Hypofractionated stereotactic radiotherapy using CyberKnife 25Gy/5fx, 5 days a week for 1 week. Anlotinib once daily (12mg/d) orally administered on days 1-14 of a 21-day cycle until disease progression or treatment intolerance. | Radiation: Hypofractionated Stereotactic Radiotherapy<br>* Hypofractionated stereotactic radiotherapy (CyberKnife, 25Gy/5fx)<br>* Other names: Hypofractionated Stereotactic Radiosurgery;Drug: Anlotinib<br>* Anlotinib once daily (12mg/d) on days 1-14 of a 21-day cycle.<br>* Other names: AL3818;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | Estimated using the Kaplan-Meier method | From the start of treatment to the date of death or the last follow-up, up to approximately 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | Estimated using the Kaplan-Meier method | From the start of treatment to the date of disease progression or death, up to approximately 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 Assessment in Neuro-Oncology (RANO) prior to progression or any further therapy. | Bimonthly up to intolerance the toxicity or progressive disease (PD), up to approximately 24 months | 
| Quality of Life score (QoL): European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) version 3.0 | EORTC QLQ-C30 (version 3.0) questionnaire to evaluate the quality of life. All scales range in score from 0 to 100. A high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems. | Bimonthly up to intolerance the toxicity or PD, up to approximately 24 months | 
| Cognitive function | Mini-Mental State Exam (MMSE, score range 0 to 30) to evaluate the cognitive function. Any score of 24 or more (out of 30) indicates a normal cognition. Below this, scores can indicate severe (≤9 points), moderate (10-18 points) or mild (19-23 points) cognitive impairment. | Bimonthly up to intolerance the toxicity or PD, up to approximately 24 months | 
| Toxicity rate | Common Terminology Criteria for Adverse Events (CTCAE) 5.0 to assess the toxicity. Estimated using an exact binomial distribution together with 95% confidence interval. | Bimonthly up to intolerance the toxicity or PD, up to approximately 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Recurrent High-grade Glioma, Hypofractionated Stereotactic Radiotherapy, Anlotinib