HSRT and IMRT Chemoradiotherapy for Newly Diagnosed GBM

Study Overview
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Brief Summary
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This study aims to evaluate the safety and effectiveness of the combination of 30Gy/5fx HSRT and 20Gy/10fx IMRT adjuvant therapy. The total biological effective dose (BED) of the PTV is 72 Gy in a ratio of alpha/beta ratio of 3, which equals to the conventional 60Gy/30fx treatment. This study can provide evidence for future non-inferiority phase III randomized controlled trials. The abbreviated course of radiotherapy can reduce the treatment time by half, benefit patients, and utilize the health resource.

Official Title
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The Combination of Hypofractionated Stereotactic Radiotherapy and Chemoradiotherapy Using Intensity-Modulated Radiotherapy for Newly Diagnosed Glioblastoma Multiforme: A Prospective, Single-Center, Single-Arm Phase II Clinical Trial

Conditions
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Glioma, Malignant

Intervention / Treatment
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* Device: Radiation
* Device: Radiation
* Drug: Temozolomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-70 years of age; Karnofsky performance status (KPS) ≥ 60 within 14 days prior to registration; Histopathologically proved diagnosis glioblastoma multiforme; Underwent surgery, gross total resection or subtotal resection; Estimated survival of at least 3 months; Hgb > 90/gL; absolute neutrophil count (ANC) > 1.5×109/L, platelets > 80×109/L; 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 in the follow-up. Exclusion Criteria: Prior invasive malignancy unless disease free; Received irradiation or other anti-tumor adjuvant therapies; Brain stem 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 nursing mothers; Participated in other trials after diagnosis; Influence factors toward oral medications; Patients with CTCAE5.0 grade 3+ bleeding within 4 weeks prior to registration; 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HSRT+IMRT+Temozolomide<br>Intensity-modulated radiotherapy 20Gy/10fx, 5 days a week for 2 weeks. Hypofractionated stereotactic radiotherapy 30Gy/5fx, 5 days a week for 1 week. Temozolomide once daily (75mg/m2/d) orally administered concurrently with radiotherapy. | Device: Radiation<br>* Intensity-modulated radiotherapy 20Gy/10fx<br>Device: Radiation<br>* Hypofractionated Stereotactic Radiotherapy 30Gy/5fx<br>Drug: Temozolomide<br>* Temozolomide 75 mg/m2 concurrently administered with RT.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | Estimated using the Kaplan-Meier method | From the start of treatment to the date of death or the last follow-up, up to approximately 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | Estimated using the Kaplan-Meier method | From the start of treatment to the date of disease progression or death, up to approximately 24 months | 
| Objective response rate (ORR) | 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 | 
| Quality of Life score (QoL) | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) version 3.0 | Bimonthly up to intolerance the toxicity or PD, up to approximately 24 months | 
| 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 | 
| Toxicity rate | Common Terminology Criteria for Adverse Events (CTCAE) 5.0 to assess the toxicity. Estimated using an exact binomial distribution together with 95% confidence interval. | Bimonthly up to intolerance the toxicity or PD, up to approximately 24 months |