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

Sponsor
Huashan Hospital (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT05611645
Collaborator
(none)
42
Enrollment
1
Location
2
Arms
38
Anticipated Duration (Months)
1.1
Patients Per Site Per Month

Study Details

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
42 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Randomized Phase II Trial of Concurrent Low-dose Bevacizumab and HSRT Versus Bevacizumab Alone for Glioblastoma at First Recurrence: HSCK-005
Actual Study Start Date :
Oct 1, 2022
Anticipated Primary Completion Date :
Dec 1, 2024
Anticipated Study Completion Date :
Dec 1, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: HSRT+Low-dose Bevacizumab

HSRT with low-dose bevacizumab every 2 weeks

Radiation: Hypofractionated Stereotactic Radiotherapy
Starting with low-dose bevacizumab, 25Gy in 5 fractions of 5 Gy each delivered on consecutive treatment days.
Other Names:
  • Hypofractionated Stereotactic Radiosurgery
  • Image-Guided Radiation Treatment (IGRT)
  • Stereotactic Radiosurgery (SRS)

    • Drug: Bevacizumab
    Staring within 2 weeks of randomization, IV 5mg/kg (experimental group) or 10mg/kg (comparison group) every two weeks until disease progression.
    Other Names:
  • anti-VEGF monoclonal antibody
  • rhuMAb VEGF
  • Avastin

    		•
    Active Comparator: Bevacizumab

    Bevacizumab every 2 weeks

    Drug: Bevacizumab
    Staring within 2 weeks of randomization, IV 5mg/kg (experimental group) or 10mg/kg (comparison group) every two weeks until disease progression.
    Other Names:
  • anti-VEGF monoclonal antibody
  • rhuMAb VEGF
  • Avastin

    		•

    Outcome Measures

    Primary Outcome Measures

    1. 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 Outcome Measures

    1. 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.

    2. 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.

    3. 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.

    4. 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.

    5. 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.

    6. 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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 70 Years
    Sexes Eligible for Study:
    All
    Accepts 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 CyberKnife Center, Department of Neurosurgery, Huashan Hospital Shanghai Shanghai China 200040

    Sponsors and Collaborators

    • Huashan Hospital

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Yun Guan, Physician, CyberKnife Center, Huashan Hospital
    ClinicalTrials.gov Identifier:
    NCT05611645
    Other Study ID Numbers:
    • KY2022-798
    First Posted:
    Nov 10, 2022
    Last Update Posted:
    Nov 10, 2022
    Last Verified:
    Nov 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    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
    Additional relevant MeSH terms:
    Glioma
    Recurrence
    Bevacizumab

    Study Results

    No Results Posted as of Nov 10, 2022