Back to resultsLow-dose Bevacizumab With HSRT vs BVZ Alone for GBM at First Recurrence
Primary Purpose
Glioma, Recurrent Glioma
Status
Active
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Hypofractionated Stereotactic Radiotherapy
Bevacizumab
Sponsored by
About this trial
This is an interventional treatment trial for Glioma
Eligibility Criteria
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.
Sites / Locations
- CyberKnife Center, Department of Neurosurgery, Huashan Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
HSRT+Low-dose Bevacizumab
Bevacizumab
Arm Description
HSRT with low-dose bevacizumab every 2 weeks
Bevacizumab every 2 weeks
Outcomes
Primary Outcome Measures
Progression-free Survival rate at 6 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 Outcome Measures
Overall Survival
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.
Progression-free Survival
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
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.
Number of Participants With Grade 3+ Toxicity rate
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.
Quality of Life score (QoL)
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
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05611645
Brief Title
Low-dose Bevacizumab With HSRT vs BVZ Alone for GBM at First Recurrence
Official Title
A Randomized Phase II Trial of Concurrent Low-dose Bevacizumab and HSRT Versus Bevacizumab Alone for Glioblastoma at First Recurrence: HSCK-005
Study Type
Interventional
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 1, 2022 (Actual)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
December 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Huashan Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
Yes
Product Manufactured in and Exported from the U.S.
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioma, Recurrent Glioma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
42 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
HSRT+Low-dose Bevacizumab
Arm Type
Experimental
Arm Description
HSRT with low-dose bevacizumab every 2 weeks
Arm Title
Bevacizumab
Arm Type
Active Comparator
Arm Description
Bevacizumab every 2 weeks
Intervention Type
Radiation
Intervention Name(s)
Hypofractionated Stereotactic Radiotherapy
Other Intervention Name(s)
Hypofractionated Stereotactic Radiosurgery, Image-Guided Radiation Treatment (IGRT), Stereotactic Radiosurgery (SRS)
Intervention Description
Starting with low-dose bevacizumab, 25Gy in 5 fractions of 5 Gy each delivered on consecutive treatment days.
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Other Intervention Name(s)
anti-VEGF monoclonal antibody, rhuMAb VEGF, Avastin
Intervention Description
Staring within 2 weeks of randomization, IV 5mg/kg (experimental group) or 10mg/kg (comparison group) every two weeks until disease progression.
Primary Outcome Measure Information:
Title
Progression-free Survival rate at 6 Months
Description
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.
Time Frame
From randomization to six months
Secondary Outcome Measure Information:
Title
Overall Survival
Description
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.
Time Frame
From randomization to last follow-up, up to approximately 24 months
Title
Progression-free Survival
Description
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.
Time Frame
From randomization to last follow-up, up to approximately 24 months
Title
Objective response rate
Description
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.
Time Frame
Bimonthly up to intolerance the toxicity or progressive disease (PD), up to approximately 24 months
Title
Number of Participants With Grade 3+ Toxicity rate
Description
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.
Time Frame
Bimonthly up to intolerance the toxicity or PD, up to approximately 24 months
Title
Quality of Life score (QoL)
Description
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.
Time Frame
Bimonthly up to intolerance the toxicity or PD, up to approximately 24 months
Title
Cognitive function
Description
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.
Time Frame
Bimonthly up to intolerance the toxicity or PD, up to approximately 24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
CyberKnife Center, Department of Neurosurgery, Huashan Hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200040
Country
China
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
35448002
Citation
Guan Y, Li J, Gong X, Zhu H, Li C, Mei G, Liu X, Pan L, Dai J, Wang Y, Wang E, Liu Y, Wang X. Safety and Efficacy of Hypofractionated Stereotactic Radiotherapy with Anlotinib Targeted Therapy for Glioblastoma at the First Recurrence: A Preliminary Report. Brain Sci. 2022 Apr 2;12(4):471. doi: 10.3390/brainsci12040471.
Results Reference
background
PubMed Identifier
33546642
Citation
Guan Y, Xiong J, Pan M, Shi W, Li J, Zhu H, Gong X, Li C, Mei G, Liu X, Pan L, Dai J, Wang Y, Wang E, Wang X. Safety and efficacy of Hypofractionated stereotactic radiosurgery for high-grade Gliomas at first recurrence: a single-center experience. BMC Cancer. 2021 Feb 5;21(1):123. doi: 10.1186/s12885-021-07856-y.
Results Reference
background
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Low-dose Bevacizumab With HSRT vs BVZ Alone for GBM at First Recurrence
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