Hypofractionated Stereotactic Radiotherapy With Anlotinib in Patients With Recurrent High-Grade Gliomas
- Conditions
- Malignant Glioma
- Interventions
- Radiation: Hypofractionated Stereotactic Radiotherapy
- Registration Number
- NCT04197492
- Lead Sponsor
- Huashan Hospital
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 22
- 18-70 years of age;
- Karnofsky performance status (KPS) ≥ 60;
- Original histopathologically proven diagnosis World Health Organization (WHO) Grade 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description HSRT With Anlotinib Hypofractionated Stereotactic Radiotherapy * 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. HSRT With Anlotinib Anlotinib * 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.
- Primary Outcome Measures
Name Time Method Overall survival (OS) From the start of treatment to the date of death or the last follow-up, up to approximately 24 months Estimated using the Kaplan-Meier method
- Secondary Outcome Measures
Name Time Method Progression-free survival (PFS) From the start of treatment to the date of disease progression or death, up to approximately 24 months Estimated using the Kaplan-Meier method
Objective response rate (ORR) Bimonthly up to intolerance the toxicity or progressive disease (PD), up to approximately 24 months 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.
Quality of Life score (QoL): European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) version 3.0 Bimonthly up to intolerance the toxicity or PD, up to approximately 24 months 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.
Cognitive function Bimonthly up to intolerance the toxicity or PD, up to approximately 24 months 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.
Toxicity rate Bimonthly up to intolerance the toxicity or PD, up to approximately 24 months Common Terminology Criteria for Adverse Events (CTCAE) 5.0 to assess the toxicity. Estimated using an exact binomial distribution together with 95% confidence interval.
Trial Locations
- Locations (1)
CyberKnife Center, Department of Neurosurgery, Huashan Hospital
🇨🇳Shanghai, Shanghai, China