Recurrent GBM With Maximal Neurosurgical Removal and Treatment With IORT

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and efficacy of the Xoft Axxent eBx System when used for single-fraction IORT for recurrent Glioblastoma. IORT using the Xoft Axxent eBx System is no worse than (non-inferior) GliaSite radiation therapy when used as stand-alone radiation treatment immediately following maximal safe neurosurgical resection in patients with recurrent glioblastoma multiforme (GBM).

Detailed Description
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Device Description: The Xoft Axxent Electronic Brachytherapy System is a device that delivers radiation at a high dose rate. It is designed for use with Axxent applicators to treat lesions, tumors, and conditions in or on the body where radiation is indicated. The Axxent System and Applicators are FDA cleared under 510(k)s K050843, K072683, K090914 and K122951. The purpose of this trial is to assess the overall survival of patients treated with the Xoft Axxent eBx System for single-fraction IORT following maximal neurosurgical resection of recurrent glioblastoma. A historical comparison will be made for surgical excision and GliaSite radiation therapy (Chan 2005), which resulted in a median OS of 9.1 months. Radiation is delivered to the target tissue (adjacent to the resection margins). It avoids treatment delays and eliminates weeks of post-surgical radiation therapy during which residual cancer cells might proliferate.

Official Title
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A Pilot Study of Patients With Recurrent Glioblastoma Treated With Maximal Safe Neurosurgical Resection, Intra-Operative Radiation Therapy (IORT) Using the Xoft® Axxent® Electronic Brachytherapy System

Conditions
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GBM, Glioblastoma, Recurrent GBM

Intervention / Treatment
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* Radiation: Intra-operative Radiation Therapy - IORT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Potentially-resectable, histologically proven recurrent GBM Subject must be ≥ 18 years of age Subject must have a Karnofsky Performance Score ≥ 70% Subject must have had a T1 weighted 3D MRI with Gadolinium enhancement within fourteen (14) days prior to surgery Women of child-bearing potential must have a negative pregnancy test within one week of IORT treatment Subjects of child-bearing potential must agree to use adequate contraceptive precautions and not to breastfeed (if applicable) Exclusion Criteria: More than three relapses Subject has multi-centric disease Subject has tumors in or near (less than 10mm from tumor margin) critical brain structures, that would exclude sufficient dose delivery to the tumor: such as: Optic Chiasm Optic Nerve Women who are pregnant or nursing. Women with child-bearing potential or sexually active men that are not willing/able to use medically acceptable forms of contraception Subject has contraindications for MRI with or without gadolinium injections Subject has contraindications for anesthesia or surgery Subject is on another therapeutic clinical trial concurrently Subject had previous radiation for GBM less than 3 month earlier Prior history of standard dose of Central Nervous System (CNS) of more than 60 Gy Intra-Operative Exclusion Criteria Frozen section does not show any sign of malignant tissue Dose at any organ at risk will exceed 10 Gy including: Chiasm Optic Nerve

Ages Eligible for Study
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Minimum Age: 18 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
Interventional Model Description: Single 20 Gy (gray) dose of electronic brachytherapy (IORT)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intra-operative Radiation Therapy - IORT<br>Intra-operative Radiation Therapy - IORT | Radiation: Intra-operative Radiation Therapy - IORT<br>* Single dose of 20 Gy<br>* Other names: Electronic Brachytherapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary endpoint is Overall Survival (OS) | The primary study goal is to assess Overall Survival (OS) of subjects treated with the Xoft Axxent Electronic Brachytherapy (eBx)® System when used for single-fraction, intra-operative radiation therapy (IORT) following maximal safe neurosurgical resection of recurrent glioblastoma for patients. | Overall Survival (OS) will be defined as the interval from enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to three years. | 
| Patients treated with Xoft IORT device median overall survival (OS) | The median and mean OS with Xoft will be calculated | Overall Survival (OS) will be defined as the interval from enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to three years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local Progression-free Survival (PFS) | Local PFS will be assessed at following intra-operative treatment with the Xoft Axxent Electronic Brachytherapy System following maximal safe neurosurgical resection. | LocPFS will be assessed at baseline, Month 2, Month 6, then every 6 months until Year 3 follow-up. | 
| Quality of Life Assessment (Fact-Br) | To assess Quality of Life Status at baseline and following intra-operative treatment with the Xoft Axxent Electronic Brachytherapy System following maximal safe neurosurgical resection. The FACT-Br questionnaire assesses subjects on a scale of 0 (minimum) to 4 (maximum), 0 equal to Not at all and 4 equal to Very Much | QOL will be assessed at baseline, Month 2, Month 6, then every 6 months until Year 3 follow-up. | 
| Karnofsky Performance Status (KPS) | To assess Karnofsky Performance Status at baseline and following intra-operative treatment with the Xoft Axxent Electronic Brachytherapy System following maximal safe neurosurgical resection. The KPS grades from 100 to 0. 0, the lower score the worst the survival for the most serious illness. 100, the higher score, survival close to normal limits, no complaints. | KPS will be assessed at baseline, Month 2, Month 6, then every 6 months until Year 3 follow-up. | 
| Radiation-related Neurotoxicity | Assess the rate of radiation-related neurotoxicity in subjects treated with the Xoft Axxent electronic Brachytherapy System when used for single-fraction, intra-operative radiation therapy treatment following maximal safe neurosurgical resection. | Radiation-related Neurotoxicity will be assessed at baseline, Month 2, Month 6, then every 6 months until Year 3 follow-up. | 
| The rate and severity of Adverse Events (AEs), Adverse Device Effects (ADEs), and Unanticipated Adverse Device Effects (UADEs) | The rate and severity of Adverse Events (AEs), Adverse Device Effects (ADEs), and Unanticipated Adverse Device Effects (UADEs) will be assessed at the time of treatment and at all follow-up visits. All Grade 3 or higher adverse events will be followed until resolution. Each event will be classified according to: Device Related Procedure Related Radiation Related | UADEs will be assessed at baseline, Month 2, Month 6, then every 6 months until Year 3 follow-up. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glioblastoma, GBM, Recurrent GBM, Recurrent Glioblastoma, IORT, Intra-Operative Radiation Therapy