Recurrent GBM Treated With Neurosurgical Resection and IORT Using the Xoft Axxent eBx System and Bevacizumab

NCT04681677 | Terminated Phase 2 DMC FDA Device

• 1 other identifier: CTPR-0017
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this trial is to assess the overall survival of patients treated with the Xoft Axxent eBx System and post-radiation adjuvant Bevacizumab for single-fraction IORT following maximal neurosurgical resection of recurrent glioblastoma. A historical comparison will be made to the results of the EBRT + Bevacizumab arm of RTOG 1205.

Conditions

Glioblastoma; Recurrent Glioblastoma; GBM; Recurrent GBM

Keywords

Bevacizumab; Glioblastoma; Recurrent Glioblastoma; GBM; Recurrent GBM; IORT; Intra-Operative Radiation Therapy; Avastin

Outcome Measures

Primary Outcomes (1)

• median overall survival (mOS)

  The median overall survival (mOS) 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 and bevacizumab and compare it to the EBRT + Bevacizumab arm of RTOG 1205.

  3 Years

Secondary Outcomes (5)

• 6 Month rate progression-free survival (PFS)

  6 Month

• tumor progression at four weeks

  4 Weeks

• Local and distant progression-free survival

  3 Years

• Quality of Life and radiation-related neurotoxicity

  3 Years

• Rate of adverse events/safety

  3 Years

Other Outcomes (1)

• imaging changes

  3 Years

Study Arms (1)

Experimental: Intra-operative Radiation Therapy - IORT

EXPERIMENTAL

Radiation: Intra-operative Radiation Therapy - IORT

Radiation: Radiation: Intra-operative Radiation Therapy - IORT; Drug: Bevacizumab

Interventions

Radiation: Intra-operative Radiation Therapy - IORT RADIATION

Single fraction, Intra-operative Radiation Therapy at the time of surgical resection of recurrent GBM followed by Bevacizumab 28-56 days after surgery.

Experimental: Intra-operative Radiation Therapy - IORT

Bevacizumab DRUG

Bevacizumab

Also known as: Avastin

Experimental: Intra-operative Radiation Therapy - IORT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject has the ability to provide written informed consent
• Subject has the willingness to comply with all study procedures for the duration of the study
• Subject has histopathologically proven diagnosis of GBM or variants (gliosarcoma, giant cell glioblastoma etc.). Subjects will be also eligible if the original histology was lower-grade glioma and a subsequent diagnosis of glioblastoma or gliosarcoma is made.
• Subjects must have shown unequivocal radiographic evidence for tumor progression by contrast-enhanced MRI within 21 days prior to enrollment
• Subjects must have passed an interval of 6 months or greater between completion of prior radiotherapy and enrollment. If subjects have not passed an interval of at least 6 months, they may still be eligible if they meet one or more of the following criteria:
• New areas of tumor outside the original radiotherapy fields as determined by the investigator, or
• Histologic confirmation of tumor through biopsy or resection, or
• Nuclear medicine imaging, MR spectroscopy, or MR perfusion imaging consistent with true progressive disease, rather than radiation necrosis obtained within 28 days of registration AND an interval of at least 90 days between completion of radiotherapy and enrollment
• The recurrent GBM must be potentially-resectable with the intent to resect such that residual tumor rim is less than 1 cm enhancing disease
• The recurrent GBM must have the appropriate dimensions to allow a Xoft applicator balloon to fit into the tumor cavity
• Subject has prior history of standard dose CNS radiation of 60 Gy in 30 fractions or 59.4 Gy in 1.8 Gy fractions, or equivalent of lower doses. Patients who have received prior treatment with non-standard RT dose and fractionation, interstitial brachytherapy, stereotactic radiosurgery, etc. are eligible as long as the criterion in 5. is met or approved by principal investigator.
• Subjects who have undergone CNS related core or needle biopsies, a minimum of 7 days must have elapsed prior to registration
• History/physical examination, including neurologic examination, within 14 days prior to enrollment (i.e. date the informed consent was signed by the patient)
• Subject must be ≥ 18 years of age
• Subject must have a Karnofsky Performance Score ≥ 60%

You may not qualify if:

• Subject has had 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 margin:
• Optic Chiasm
• Optic Nerve
• Subject has infratentorial, or leptomeningeal evidence of recurrent disease
• Subject has recurrent or persistent tumor greater than 6 cm in maximum diameter
• Subject underwent prior therapy with an inhibitor of VEGF or VEGFR (including Bevacizumab)
• Subject suffered from prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 1 year (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible).
• 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.
• Subject has contraindications for anesthesia or surgery.
• Subject is on another therapeutic clinical trial concurrently.
• Subject suffers severe, active co-morbidity, defined as follows:
• Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months prior to enrollment

Sponsors & Collaborators

• Xoft, Inc.: lead
• Icad, Inc.: collaborator

Study Sites (1)

Providence Saint John's Health Center

Santa Monica, California, 90404, United States

Location

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MeSH Terms

Conditions

Glioblastoma

Interventions

Bevacizumab

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Santosh Kesari, MD

  Saint John's Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single arm, prospective, multi-center, non-randomized, historical control, non-inferiority study of subjects treated with single fraction, Intra-Operative Radiation Therapy at the time of maximal resection for recurrent GBM. Treatment with Bevacizumab will be initiated 28-56 days after surgery depending on surgical wound healing assessment at the discretion of the treating investigator.

Study Record Dates

• First Submitted: December 17, 2020
• First Posted: December 23, 2020
• Study Start: November 2, 2021
• Primary Completion: April 24, 2024
• Study Completion: April 24, 2024
• Last Updated: April 26, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)