Post-operative Adjuvant Therapy w/wo GammaTile + Systemic Therapy

NCT05900908 | Withdrawn Phase 4 DMC FDA Device

• 1 other identifier: GTM-104
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

To compare surgical tumor removal and GammaTile therapy followed by adjuvant systemic therapy (bevacizumab or lomustine) to surgical tumor removal followed by adjuvant systemic therapy (bevacizumab or lomustine) without GammaTile therapy.

Conditions

Glioblastoma

Keywords

Brain; Tumor; Glioblastoma; Recurrent; Cancer; Metastases; GammaTile; Radiation; Cs-131

Outcome Measures

Primary Outcomes (1)

• Median Overall Survival (OS) from the time of surgery up to 2 years post surgery.

  Analysis of primary outcome measure will include the intent to treat population.

  up to 2 years

Secondary Outcomes (10)

• Overall Survival

  up to 2 years

• Progression free survival (PFS)

  up to 2 years

• Change in Quality of Life (QOL)

  up to 1.5 years

• Assessment of Neurocognitive Function

  up to 1.5 years

• Functional Status-Karnofsky Performance Scale (KPS)

  up to 2 years

Study Arms (2)

surgical tumor removal and GammaTile therapy followed by adjuvant systemic therapy

EXPERIMENTAL

surgical tumor removal and GammaTile therapy followed by adjuvant systemic therapy

Device: Gamma Tile-Surgically Targeted Radiation Therapy (STaRT)

surgical tumor removal followed by adjuvant systemic therapy

ACTIVE COMPARATOR

surgical tumor removal followed by adjuvant systemic therapy

Radiation: Stereotactic Radiation Therapy

Interventions

Gamma Tile-Surgically Targeted Radiation Therapy (STaRT) DEVICE

GammaTiles are a permanently implanted radiation device consisting of Cs-131 seeds positioned within a collagen tile

Also known as: Carrier Tile Brachytherapy Therapy (CTBT)

surgical tumor removal and GammaTile therapy followed by adjuvant systemic therapy

Stereotactic Radiation Therapy RADIATION

External Beam Radiation Therapy

surgical tumor removal followed by adjuvant systemic therapy

Eligibility Criteria

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

You may qualify if:

• Patients aged 18 years old and above. Eligibility is restricted to this age group given that the battery of neurocognitive tests utilized in this protocol are not developed or validated for use in a younger population.
• History of a histopathologically and molecularly confirmed glioblastoma, per Consortium to Inform Molecular and Practical Approaches to Central Nervous System Tumor Taxonomy (c-IMPACT-NOW) criteria ("diffuse astrocytic glioma, IDH-wildtype, with molecular features of glioblastoma, World Health Organization \[WHO\] grade IV"; this requires presence of amplification of EGFR, whole chromosome 7 gain AND whole chromosome 10 loss, or Telomerase reverse transcriptase (TERT) promoter mutation.
• Patients for which bevacizumab or lomustine are reasonable systemic treatments following surgery.
• Eligible patients must be experiencing a known or suspected first recurrence of a supratentorial GBM following prior first-line concurrent TMZ and RT (allowed hypofractionation of prior RT dose ≥ 40 Gray \[Gy\] of a planned 60 Gy dose) and at least one cycle of adjuvant TMZ. RT must have concluded \>45 days prior to enrollment, and most recent adjuvant TMZ treatment(s) must have been concluded or terminated \>10 days prior to enrollment. Prior adjuvant TMZ cycles up to 12, prior adjuvant tumor-treating fields (TTF), and prior External Beam Radiotherapy (EBRT) doses via proton or photon treatments up to 72 Gy equivalent are allowed. Note: This includes infratentorial recurrences of tumors that were supratentorial at diagnosis. Tumors the were infratentorial at diagnosis are excluded.
• Eligible tumors are defined as the following:
• Supratentorial
• A bi-dimensionally measurable lesion of at least 10 mm, visible on two or more axial slices 5 mm apart.
• The pre-operative tumor (including enhanced and unenhanced tumor) planned for resection that is 60 mm2 or less in maximum cross section.
• Tumor that in the opinion of the enrolling neurosurgeon is amenable to attempted gross total resection (GTR). Prior diagnostic biopsy allowed.
• Anticipated GammaTile placement (i.e., closest aspect of post resection tumor bed that is anticipated to receive GammaTile placement) that is \> 15mm from the optic chiasm or brainstem.
• Multifocal enhancing disease is allowed if it can be fully encompassed in one operative bed while meeting criterion a-e.
• Ability to complete an MRI of the head with and without contrast, and a non-contrast CT.
• All subjects fluent in English will complete neurocognitive evaluations. Patients not fluent in English are allowed on trial but will not take neurocognitive tests as comparative data is only available from tests in the English language.
• Tumor O-6-methylguanine-deoxyribonucleic acid (DNA) methyltransferase (MGMT) methylation status must be available from any prior GBM tumor specimen; results of routinely used methods for MGMT methylation testing (e.g., mutagenically separated polymerase chain reaction \[MSPCR\] or quantitative polymerase chain reaction \[PCR\]) are acceptable and results can be from a local lab or central lab used by a prior study.
• Suspicion of suspected tumor recurrence is on imaging and/or histologic grounds. If imaging, at a minimum a contrast-enhanced MRI scan ≤21 days prior to registration (at the time of randomization) should meet Response Assessment in Neuro-Oncology (RANO) criteria.

You may not qualify if:

• Any previous treatment for recurrent GBM.
• Patients with suspected or confirmed radiation necrosis.
• Known somatic tumor mutation in IDH1 or IDH2 gene. If not previously completed, sequencing of the IDH1 and IDH2 genes is not required to determine trial eligibility.
• Known germline DNA repair defect (mismatch repair deficiency, POLE mutation, e.g.). If not previously completed, germline sequencing is not required to determine trial eligibility.
• Patients not appropriate for treatment with bevacizumab or lomustine, in the opinion of the investigator or medical team.
• Patients for whom any additional treatment is planned in the absence of recurrent or progressive disease.
• Leptomeningeal disease not expected to be encompassed by the surgical resection.
• History of treatment with carmustine implants (Gliadel)
• Previous or concurrent bevacizumab therapy for treatment of tumor. Use of bevacizumab is allowed for reducing edema. Must be off of bevacizumab for at least 28 days prior to surgery.
• If bevacizumab is pre-planned for adjuvant systemic treatment, the following contraindications to the use of bevacizumab, must be absent. (Note: If any of these contraindications exist, the use of lomustine must be considered as the systemic agent. If both bevacizumab and lomustine are inappropriate in the treating physician's opinion, the patient must be excluded).
• Clinically Significant Cardiovascular Disease Defined as follows: Inadequately controlled hypertension (i.e., systolic blood pressure (SBP) \> 160 mm Hg and/or diastolic blood pressure (DBP) \> 90 mm Hg despite antihypertensive therapy).
• History of cerebrovascular accident (CVA) ≤ 180 days.
• Myocardial infarction or unstable angina ≤ 180 days.
• Pulmonary embolism ≤180 days
• Evidence or history of bleeding diathesis (greater than normal risk of bleeding, i.e., Hereditary Hemorrhagic Telangiectasia Type I or HHT-1) or coagulopathy in the absence of therapeutic anti-coagulation or any hemorrhage/bleeding event \> Grade 3

Sponsors & Collaborators

• GT Medical Technologies, Inc.: lead

MeSH Terms

Conditions

Glioblastoma; Neoplasms; Recurrence; Neoplasm Metastasis

Interventions

Radiosurgery

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplastic Processes

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 25, 2023
• First Posted: June 13, 2023
• Study Start: May 1, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2028
• Last Updated: April 10, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share