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

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

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.

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.

Inclusion Criteria:

1. 18-70 years of age;
2. Karnofsky performance status (KPS) ≥ 60;
3. Original histopathologically proven diagnosis World Health Organization (WHO) Grade 4 glioma;
4. 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;
5. Measurable disease;
6. Estimated survival of at least 3 months;
7. 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;
8. Signed informed consent form;
9. Agreed to participate the follow-up.

Exclusion Criteria:

1. Prior invasive malignancy unless disease free;
2. Received re-irradiation;
3. More than 3 relapses or evidence of subtentorial recurrent disease or tumor greater than 6 cm in maximum diameter;
4. Prior therapy with an inhibitor of vascular endothelial growth factor (VEGF) or VEGFR;
5. Pregnancy or or nursing mothers;
6. Participated in other trials after diagnosis of recurrent;
7. Influence factors toward oral medications;
8. Patients with CTCAE5.0 grade 3+ bleeding;
9. 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%;
10. Long-term unhealed wounds or fractures;
11. History of organ transplantation;
12. Serious diseases that endanger patients' safety or affect patients' completion of research,according to the researchers' judgment.