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

Glioma Clinical Trial

Official title:

A Randomized Phase II Trial of Concurrent Low-dose Bevacizumab and HSRT Versus Bevacizumab Alone for Glioblastoma at First Recurrence: HSCK-005

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05611645
• Other study ID #: KY2022-798
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: October 1, 2022
• Est. completion date: December 2025

Study information

• Verified date: November 2022
• Source: Huashan Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 42
• Est. completion date: December 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Glioma
• Recurrence
• Recurrent Glioma

Intervention

Radiation:
• Hypofractionated Stereotactic Radiotherapy
Starting with low-dose bevacizumab, 25Gy in 5 fractions of 5 Gy each delivered on consecutive treatment days.

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

Locations

Country	Name	City	State
China	CyberKnife Center, Department of Neurosurgery, Huashan Hospital	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Huashan Hospital

Country where clinical trial is conducted

China, 

References & Publications (2)

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). pii: 471. doi: 10.3390/brainsci12040471. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	From randomization to six months
Secondary	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.	From randomization to last follow-up, up to approximately 24 months
Secondary	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.	From randomization to last follow-up, up to approximately 24 months
Secondary	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.	Bimonthly up to intolerance the toxicity or progressive disease (PD), up to approximately 24 months
Secondary	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.	Bimonthly up to intolerance the toxicity or PD, up to approximately 24 months
Secondary	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.	Bimonthly up to intolerance the toxicity or PD, up to approximately 24 months
Secondary	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.	Bimonthly up to intolerance the toxicity or PD, up to approximately 24 months