Glioma, Recurrent Glioma
Conditions
Brief summary
This randomized phase II trial studies how well lose dose bevacizumab with Hypofractionated Stereotactic Radiotherapy (HSRT) works versus bevacizumab alone in treating patients with glioblastoma at first recurrence. The primary endpoint is 6-month progress-free survivaloverall survival after the treatment. Secondary endpoints included overall survival, objective response rate, cognitive function, quality of life and toxicity.
Detailed description
To establish an improvement in 6-month pfs in recurrent glioblastoma patients receiving low-dose bevacizumab and re-irradiation compared with patients receiving bevacizumab alone.
Interventions
Starting with low-dose bevacizumab, 25Gy in 5 fractions of 5 Gy each delivered on consecutive treatment days.
DRUGBevacizumab
Staring within 2 weeks of randomization, IV 5mg/kg (experimental group) or 10mg/kg (comparison group) every two weeks until disease progression.
Sponsors
Huashan Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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, maximal diameter on T1+C MRI ≤ 3.5 cm; * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival rate at 6 Months | From randomization to six months | Prgression was defined using Response Assessment in Neuro-Oncology (RANO) Criteria. Progression-free at 6 months means patient alive without progression at 6 months. Survival rates are estimated by the Kaplan-Meier method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | From randomization to last follow-up, up to approximately 24 months | Prgression was defined using Response Assessment in Neuro-Oncology (RANO) Criteria. Progression-free survival time is defined as time from randomization to the date of first progression, death, or last known follow-up (censored). Progression-free survival rates are estimated using the Kaplan-Meier method. |
| Objective response rate | 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. |
| Overall Survival | From randomization to last follow-up, up to approximately 24 months | Survival time is defined as time from randomization to the date of death from any cause or last known follow-up (censored). Survival rates are estimated by the Kaplan-Meier method. |
| Quality of Life score (QoL) | 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. |
| Number of Participants With Grade 3+ Toxicity rate | Bimonthly up to intolerance the toxicity or PD, up to approximately 24 months | Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Grade refers to the severity of the AE. Estimated using an exact binomial distribution together with 95% confidence interval. The difference between the two groups will be tested using a chi square test. |
Countries
China
Outcome results
None listed