GlioblastomaPhase 4PATHWAySNCT05900908
Post-operative Adjuvant Therapy w/wo GammaTile + Systemic Therapy
A Phase 4 study testing Gamma Tile-Surgically Targeted Radiation Therapy (STaRT) and Stereotactic Radiation Therapy in people with Glioblastoma, run by GT Medical Technologies, Inc..
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma
- What is being tested?
- Gamma Tile-Surgically Targeted Radiation Therapy (STaRT) and Stereotactic Radiation Therapy
- Type of treatment
- Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- May 2025to Jun 2028
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 34Show fewer
- 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.
- Concomitant systemic or local anti-cancer medications or treatments, other than those on this protocol, are prohibited in this study in the absence of progression.
- Patients can be on a stable or decreasing dose of steroids for 1 week before the screening MRI. Utilization of the lowest useful dose and shortest useful course are encouraged.
- Karnofsky Performance Scale (KPS) score of ≥ 70 documented within ± 21 days of signing consent.
- Eastern Cooperative Oncology Group Performance Score (ECOG-PS) of <2 documented ≤ 21 days of signing consent.
- Blood test results ≤ 21 days prior to surgery (can be re-run prior to surgery):
- Leukocytes ≥ 2,500/mm3
- Absolute neutrophil count ≥ 1,500/mm3
- Absolute lymphocyte count ≥ 800/mm3
- Platelets ≥ 75,000/mm3
- Hemoglobin ≥ 8 g/dL
- Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (however, patients with known Gilbert disease who have serum bilirubin level ≤ 3 x ULN may be enrolled)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])
- 2.5 x ULN
- Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) ≤ 2.5 x ULN
- Alkaline phosphatase ≤ 2.5 x ULN
- Creatinine clearance ≥ 50 mL/min/1.73 m2 by Cockcroft-Gault
- Women of childbearing potential must have a negative serum or urine pregnancy test ≤7 days prior to randomization. Women must be willing to notify investigator immediately if they become pregnant at any time during the trial period. They must be willing to use a form of contraception to prevent pregnancy during treatment.
- Willingness and ability to provide written informed consent or have their legally authorized representative provide consent and Health Insurance Portability and Accountability (HIPAA) authorization for them if they physically are unable to sign prior to performance of any study-related procedure.
- Availability of prior radiotherapy treatment plan details in Digital Imaging and Communications in Medicine (DICOM) format is desired but not required for study participation.
Who cannot join
- 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.
Show all 27Show fewer
- 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
- 28 days prior to registration. Note: Patients with full-dose anticoagulants are eligible provided the patient has been on a stable dose for ≥14 days.
- Active wound, a serious or non-healing wound, an active ulcer or untreated bone fracture.
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess ≤ 180 days prior to consenting.
- Previous or current treatment with an investigational or FDA approved systemic therapy for glioblastoma other than external beam radiation (proton or photon), temozolomide (Temodar®), or tumor treatment fields (Optune®) (e.g., other forms of systemic therapy, targeted therapeutics, immunotherapy).
- Sensitivity to bovine (cow) derived materials including collagen products.
- Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen are excluded from this trial.
- Severe infections ≤ 21 days prior to signing consent including, but not limited to, hospitalization for complications of infection, bacteremia, viral infections (COVID-19 [Corona Virus Disease 2019], Hepatitis B or C, Human Immunodeficiency Virus [HIV]) or severe pneumonia.
- Major surgical procedure ≤21 days prior to protocol surgery or anticipation of need for a major surgical procedure during the course of study treatment.
- Uncontrolled intercurrent illness including, but not limited to, uncontrolled hypertension (systolic blood pressure >140 mm Hg or diastolic blood pressure >90 mm Hg) despite optimal medical management; myocardial infarction less than 6 months before the planned surgery date; arterial thrombotic or embolic events, such as cerebrovascular accident (including transient ischemic attacks) or pulmonary embolism 180 days before the planned surgery date, or psychiatric illness/social situations that would impair understanding or limit compliance with study requirements, including ability to complete neurocognitive assessments and quality of life questionnaires, and returning for follow-up care
- Any concomitant therapy that, in the investigator's opinion, would interfere with the evaluation of the safety or efficacy of the study device.
- Women who are pregnant or nursing are excluded from this study.
- Patients who experienced a toxicity of grade ≥ 3 (CTCAE v5) from prior GBM treatment, unless they have sufficiently recovered as evidenced by a drop to grade ≤2 or have full resolution.
About this study
Official title: A Randomized Controlled Trial of Surgical Resection With GammaTile Therapy and Adjuvant Systemic Therapy Compared to Surgical Resection and Adjuvant Systemic Therapy at First Recurrence in Glioblastoma.
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
- Being tested
- Gamma Tile-Surgically Targeted Radiation Therapy (STaRT), Stereotactic Radiation Therapy
- Keywords
- Brain, Tumor, Glioblastoma, Recurrent, Cancer, Metastases, GammaTile, Radiation, Cs-131
- Medical subject headings
- Glioblastoma, Neoplasms, Recurrence, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Gamma Tile-Surgically Targeted Radiation Therapy (STaRT)Device
Also called Carrier Tile Brachytherapy Therapy (CTBT)
GammaTiles are a permanently implanted radiation device consisting of Cs-131 seeds positioned within a collagen tile
Stereotactic Radiation TherapyRadiation
External Beam Radiation Therapy
| Study group | Role | What they receive |
|---|---|---|
| surgical tumor removal and GammaTile therapy followed by adjuvant systemic therapy | Experimental | surgical tumor removal and GammaTile therapy followed by adjuvant systemic therapy Receives: 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 Receives: Radiation: Stereotactic Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: up to 2 years
Secondary outcomes (10)
Overall Survival
A measure of median overall survival for the per protocol population
Measured: up to 2 years
Progression free survival (PFS)
A measure of time from surgery to any failure, local or distant.
Measured: up to 2 years
Change in Quality of Life (QOL)
Functional Assessment of Cancer Therapy-Brain (FACT-Br)
Measured: up to 1.5 years
Assessment of Neurocognitive Function
Hopkins Verbal Learning Test-Revised [HVLT-R]
Measured: up to 1.5 years
Functional Status-Karnofsky Performance Scale (KPS)
An assessment of functional impairment. Score 0 to 100, with 100 being no impairment of performance
Measured: up to 2 years
Proportion of subjects with evidence of radiation necrosis (RN)
A measure of patients who experience radiation necrosis post-surgery.
Measured: up to 2 years
Proportion of subjects with evidence of surgical site wound infection
A measure of patients who experience surgical site wound infection
Measured: Up to 1.5 months
Proportion of subjects with evidence of a surgical site dural closure-related cerebral spinal fluid (CSF) leak
A measure of patients who experience surgical site dural closure-related cerebral spinal fluid (CSF) leak
Measured: Up to 1.5 months
Post-surgery length of hospital stay of study subjects
A measure in days of the length of hospital stay post surgery.
Measured: Up to 1.5 months
Rate of re-admission
A measure of patients re-admitted to the hospital +/- 30 days post surgery.
Measured: Up to 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2023
- Study startMay 2025 (estimated)
- Primary completionJun 2026 (estimated)
- Study completionJun 2028 (estimated)
Why it stopped: Study is being withdrawn in favor of a different study schema to be launched later this year.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- GT Medical Technologies, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05900908
- Sponsor's protocol ID
- GTM-104
- Acronym
- PATHWAyS
- Status last verified
- Apr 2025
- First submitted
- 25 May 2023
- Last updated
- 10 Apr 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Trial of Surgical Resection With GammaTile Therapy and Adjuvant Systemic Therapy Compared to Surgical Resection and Adjuvant Systemic Therapy at First Recurrence in Glioblastoma.
- ClinicalTrials.gov ID
- NCT05900908
- Acronym / sponsor ID
- PATHWAyS / GTM-104
- Conditions
- Glioblastoma
- Keywords
- Brain, Tumor, Glioblastoma, Recurrent, Cancer, Metastases, GammaTile, Radiation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study is being withdrawn in favor of a different study schema to be launched later this year.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- GT Medical Technologies, Inc.Industry (pharma, biotech, devices)
- Study start
- May 2025 (estimated)
- Primary completion
- Jun 2026 (estimated)
- Study completion
- Jun 2028 (estimated)
- First posted
- 13 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| surgical tumor removal and GammaTile therapy followed by adjuvant systemic therapy | Experimental | Device: Gamma Tile-Surgically Targeted Radiation Therapy (STaRT)surgical tumor removal and GammaTile therapy followed by adjuvant systemic therapy |
| surgical tumor removal followed by adjuvant systemic therapy | Active comparator | Radiation: Stereotactic Radiation Therapysurgical tumor removal followed by adjuvant systemic therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (34 listed)
- 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:
Key exclusion criteria (27 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Gamma Tile-Surgically Targeted Radiation Therapy (STaRT)Also: Carrier Tile Brachytherapy Therapy (CTBT)GammaTiles are a permanently implanted radiation device consisting of Cs-131 seeds positioned within a collagen tile | Device | surgical tumor removal and GammaTile therapy followed by adjuvant systemic therapy |
| Stereotactic Radiation TherapyExternal Beam Radiation Therapy | Radiation | surgical tumor removal followed by adjuvant systemic therapy |
Primary outcome
Median Overall Survival (OS) from the time of surgery up to 2 years post surgery.
Time frame: up to 2 years
Analysis of primary outcome measure will include the intent to treat population.
10 secondary outcomes
Overall Survival
Time frame: up to 2 years
Progression free survival (PFS)
Time frame: up to 2 years
Change in Quality of Life (QOL)
Time frame: up to 1.5 years
Assessment of Neurocognitive Function
Time frame: up to 1.5 years
Functional Status-Karnofsky Performance Scale (KPS)
Time frame: up to 2 years
Proportion of subjects with evidence of radiation necrosis (RN)
Time frame: up to 2 years
Proportion of subjects with evidence of surgical site wound infection
Time frame: Up to 1.5 months
Proportion of subjects with evidence of a surgical site dural closure-related cerebral spinal fluid (CSF) leak
Time frame: Up to 1.5 months
Post-surgery length of hospital stay of study subjects
Time frame: Up to 1.5 months
Rate of re-admission
Time frame: Up to 1 month
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Apr 2025.
- Individual participant dataSharing planned: No
Related trials for Glioblastoma
RecruitingPhase 1
A Feasibility Study to Evaluate the Safety of the TheraSphere Glioblastoma (GBM) Device in Patients With Recurrent GBM
Glioblastoma Multiforme, Recurrent Glioblastoma
RecruitingPhase 1
A Study of RNA-lipid Particle (RNA-LP) Vaccines for Newly Diagnosed Pediatric High-Grade Gliomas (pHGG) and Adult Glioblastoma (GBM)
Adult Glioblastoma, High Grade Glioma
Not yet recruitingPhase 1
IL-8 Receptor-modified CD70 CAR T Cell Therapy in CD70+ Newly Diagnosed and Recurrent Pediatric High-grade Glioma (pHGG) and Newly Diagnosed Diffuse Intrinsic Pontine Glioma (ndDIPG)
High-grade Glioma, Diffuse Intrinsic Pontine Glioma
Not yet recruitingPhase 1
Immune Modulatory DC Vaccine Against Brain Tumor
Diffuse Intrinsic Pontine Glioma or Glioblastoma
Recruiting
Tear Fluid for the Detection of Tumor-associated Extracellular Vesicles in Glioblastoma Patients
Glioblastoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Gamma Tile-Surgically Targeted Radiation Therapy (STaRT) and Stereotactic Radiation Therapy in people with Glioblastoma, run by GT Medical Technologies, Inc..
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 34 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 10 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Median Overall Survival (OS) from the time of surgery up to 2 years post surgery. (time frame: up to 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Apr 2025.