Clinical trial NCT05611645: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Glioma
Recurrent Glioma
Lead sponsor: Huashan Hospital
Sponsor class: OTHER
First posted: 2022-11-10
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Progression-free Survival rate at 6 Months
timeFrame: From randomization to six months
Secondary outcomes:
measure: Overall Survival
timeFrame: From randomization to last follow-up, up to approximately 24 months
measure: Progression-free Survival
timeFrame: From randomization to last follow-up, up to approximately 24 months
measure: Objective response rate
timeFrame: Bimonthly up to intolerance the toxicity or progressive disease (PD), up to approximately 24 months
measure: Number of Participants With Grade 3+ Toxicity rate
timeFrame: Bimonthly up to intolerance the toxicity or PD, up to approximately 24 months
measure: Quality of Life score (QoL)
timeFrame: Bimonthly up to intolerance the toxicity or PD, up to approximately 24 months
measure: Cognitive function
timeFrame: Bimonthly up to intolerance the toxicity or PD, up to approximately 24 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: CyberKnife Center, Department of Neurosurgery, Huashan Hospital
state: Shanghai
Study officials:
References:
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.
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.