Proton and Heavy Ion Beam Radiation vs. Photon Beam Radiation for Newly Diagnosed Glioblastoma.

Study Overview
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Brief Summary
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This is a multi-center prospective phase 3 clinical trial to explore the efficacy and side effects of standard-dose photon radiation versus standard-dose proton radiation versus carbon ion boost plus standard proton radiation for newly diagnosed glioblastoma. The patients enrolled will be randomly allocated with 1:1:1 to three group: Control Group, standard-dose photon radiotherapy; Study Group A, standard-dose proton radiotherapy; Study Group B, standard-dose proton radiotherapy plus induction carbon-ion radiotherapy boost. The primary endpoint is overall survival (OS).

Detailed Description
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This multi-center prospective phase 3 clinical trial will enroll 369 patients with newly diagnosed glioblastoma. Patients will be randomly allocated with 1:1:1 to three groups: Control Group, standard-dose photon radiotherapy (60 Gy); Study Group A, standard-dose proton radiotherapy (60 GyE); Study Group B, standard-dose proton radiotherapy (60 GyE) plus induction carbon-ion radiotherapy boost (15GyE/3F). All patients will receive concurrent and adjuvant temozolomide according to the Stupp protocol. The primary endpoint is overall survival (OS). The secondary endpoint is progression-free survival, side effect and quality life.

Official Title
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Proton and Heavy Ion Beam Radiation Versus Photon Beam Radiation for Newly Diagnosed Glioblastoma: A Multi-center Prospective Phase 3 Randomized Control Clinical Trial.

Conditions
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Glioblastoma

Intervention / Treatment
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* Radiation: Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age> 18 years old and <80 years old Pathologically confirmed newly-diagnosed GBM Redisual lesion after subtotal resection, partial resection, or biopsy No dissemination or metastasis in the spinal canal, single lesion, supratentorial lesion ECOG score 0-1 Sign the informed consent form before starting the research Exclusion Criteria: No pathological confirmed evidence of GBM Multiple lesions or distant spread indicated by imaging studies Receive conventional photon/proton/carbon ion radiation therapy on the head Received intracranial radioactive particle implantation A history of malignant tumors or multiple primary tumors (except skin basal cell carcinoma) Positive pregnancy test for women of childbearing age With the accompanying diseases or conditions affect the safety of patients during normal enrollment or research Active mental disorders or other mental disorders that affect the patients ability to sign informed consent and understand Uncontrolled active infection

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Standard-dose Photon Radiotherapy<br>The patients will receive standard-dose photon radiation (60Gy/30F for high-risk area) with concurrent temozolomide (75mg/m2, qd), adjuvant temozolomide (150-200mg/m2, qd, D1-5, 28d/cycle) | Radiation: Radiotherapy<br>* Multimodal brain imaging-guided radiotherapy using different beams<br>|
| Experimental: Standard-dose Proton Radiotherapy<br>The patients will receive standard-dose proton radiation (60GyE/30F for high-risk area) with concurrent temozolomide (75mg/m2, qd), adjuvant temozolomide (150-200mg/m2, qd, D1-5, 28d/cycle). | Radiation: Radiotherapy<br>* Multimodal brain imaging-guided radiotherapy using different beams<br>|
| Experimental: Standard-dose Proton Radiotherapy plus Carbon-Ion Boost<br>The patients will receive carbon-ion radiation boost (15GyE/3F for residual lesion) priot to standard-dose proton radiation (60GyE/30F for high-risk area) with concurrent temozolomide (75mg/m2, qd), then adjuvant temozolomide (150-200mg/m2, qd, D1-5, 28d/cycle). | Radiation: Radiotherapy<br>* Multimodal brain imaging-guided radiotherapy using different beams<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | The interval from randomization to death | From the pathological confirmation to death, a median of 3 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | The interval from randomization to progression or death | From randomization to tumor progression, with a median of 3 years. | 
| Toxicities | The scores of toxicities are based on CTCAE criteria, which refers to Common Terminology Criteria for Adverse Events. | From start to 12 months after completion of radiotherapy. | 
| Recognitive Function | The assessment of recognitive function is based on MMSE criteria, which refers to Mini-Mental State Examination. | From initiation of radiotherapy to 12 months after completion of radiotherapy. | 
| Life Quality | The assessment of life quality is based on ADL criteria, which refers to Activities of Daily Living. | From initiation of radiotherapy to 12 months after completion of radiotherapy. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glioblastoma, Carbon-ion Radiotherapy, Proton Radiotherapy, Photon Radiotherapy, Overall Survival