Low-dose Bevacizumab With HSRT vs BVZ Alone for GBM at First Recurrence

NCT ID: NCT05611645

Last Updated: 2022-11-10

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-10-01
• Study Completion Date: 2025-12-31

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.

Conditions

Glioma; Recurrent Glioma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

HSRT+Low-dose Bevacizumab

HSRT with low-dose bevacizumab every 2 weeks

Group Type: EXPERIMENTAL

Hypofractionated Stereotactic Radiotherapy

Intervention Type: RADIATION

Starting with low-dose bevacizumab, 25Gy in 5 fractions of 5 Gy each delivered on consecutive treatment days.

Bevacizumab

Intervention Type: DRUG

Staring within 2 weeks of randomization, IV 5mg/kg (experimental group) or 10mg/kg (comparison group) every two weeks until disease progression.

Bevacizumab

Bevacizumab every 2 weeks

Group Type: ACTIVE_COMPARATOR

Bevacizumab

Intervention Type: DRUG

Staring within 2 weeks of randomization, IV 5mg/kg (experimental group) or 10mg/kg (comparison group) every two weeks until disease progression.

Interventions

Hypofractionated Stereotactic Radiotherapy

Starting with low-dose bevacizumab, 25Gy in 5 fractions of 5 Gy each delivered on consecutive treatment days.

Intervention Type: RADIATION

Bevacizumab

Staring within 2 weeks of randomization, IV 5mg/kg (experimental group) or 10mg/kg (comparison group) every two weeks until disease progression.

Intervention Type: DRUG

Other Intervention Names

Hypofractionated Stereotactic Radiosurgery; Image-Guided Radiation Treatment (IGRT); Stereotactic Radiosurgery (SRS); anti-VEGF monoclonal antibody; rhuMAb VEGF; Avastin

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Huashan Hospital

OTHER

Sponsor Role: lead

Responsible Party

Yun Guan

Physician, CyberKnife Center

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

CyberKnife Center, Department of Neurosurgery, Huashan Hospital

Shanghai, Shanghai Municipality, China

Countries

China

References

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.

Reference Type: BACKGROUND

PMID: 35448002 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 33546642 (View on PubMed)

Other Identifiers

KY2022-798

Identifier Type: -

Identifier Source: org_study_id