Recurrent GBM With Maximal Neurosurgical Removal and Treatment With IORT

Glioblastoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04763031
• Other study ID #: PMC-3422401
• Status: Terminated
• Phase: N/A
• Start date: March 5, 2021
• Est. completion date: November 3, 2023

Study information

• Verified date: November 2023
• Source: Parkridge Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Description:

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: November 3, 2023
• Est. primary completion date: November 3, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Potentially-resectable, histologically proven recurrent GBM

2. Subject must be = 18 years of age

3. Subject must have a Karnofsky Performance Score = 70%

4. Subject must have had a T1 weighted 3D MRI with Gadolinium enhancement within fourteen (14) days prior to surgery

5. Women of child-bearing potential must have a negative pregnancy test within one week of IORT treatment

6. Subjects of child-bearing potential must agree to use adequate contraceptive precautions and not to breastfeed (if applicable)

Exclusion Criteria:

1. More than three relapses

2. Subject has multi-centric disease

3. 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:

1. Optic Chiasm

2. Optic Nerve

4. 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

5. Subject has contraindications for MRI with or without gadolinium injections

6. Subject has contraindications for anesthesia or surgery

7. Subject is on another therapeutic clinical trial concurrently

8. Subject had previous radiation for GBM less than 3 month earlier

9. Prior history of standard dose of Central Nervous System (CNS) of more than 60 Gy

Intra-Operative Exclusion Criteria

1. Frozen section does not show any sign of malignant tissue

2. Dose at any organ at risk will exceed 10 Gy including:

1. Chiasm

2. Optic Nerve

Related Conditions & MeSH terms

• GBM
• Glioblastoma
• Recurrence
• Recurrent GBM

Intervention

Radiation:
• Intra-operative Radiation Therapy - IORT
Single dose of 20 Gy

Locations

Country	Name	City	State
United States	Parkridge Medical Center - Neurosurgery	Chattanooga	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Parkridge Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (31)

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* Note: There are 31 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.

External Links

•   Clinical benefit from resection of recurrent glioblastomas: results of a multicenter study including 503 patients with recurrent glioblastomas undergoing surgical resection
•   Development of multiple lesions during radiation therapy and chemotherapy in patients with gliomas
•   European Association for Neuro-Oncology (EANO) guideline on the diagnosis and treatment of adult astrocytic and oligodendroglial gliomas.
•   Extent of resection in newly diagnosed glioblastoma: Impact of a specialized neuro-oncology care center.
•   Management of glioblastoma after recurrence: A changing paradigm.
•   Novel Use of the Contura for High Dose Rate Cranial Brachytherapy
•   Patterns of failure following treatment for glioblastoma multiforme and anaplastic astrocytoma
•   Polymodal therapy for high grade gliomas: a case report of favourable outcomes following intraoperative radiation therapy.
•   Reoperation for recurrent glioblastoma and anaplastic astrocytoma.
•   Reoperation in the treatment of recurrent intracranial malignant gliomas.
•   Retreatment of intracranial gliomas
•   Supratentorial malignant glioma: patterns of recurrence and implications for external beam local treatment.
•   The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary
•   The Phenomenon of Long-Term Survival in Glioblastoma Patients. Part I: The Role of Clinical and Demographic Factors and an IDH1 Mutation
•   The Value of Glioma Extent of Resection in the Modern Neurosurgical Era
•   Treatment outcome of patients with recurrent glioblastoma multiforme: a retrospective multicenter analysis