Phase
Condition
Gliomas
Neoplasm Metastasis
Astrocytoma
Treatment
Gamma Tile-Surgically Targeted Radiation Therapy (STaRT)
Stereotactic Radiation Therapy
Clinical Study ID
Study Summary
Eligibility Criteria
Inclusion
Inclusion Criteria:
Patients aged 18 years old and above. Eligibility is restricted to this age groupgiven that the battery of neurocognitive tests utilized in this protocol are notdeveloped or validated for use in a younger population.
History of a histopathologically and molecularly confirmed glioblastoma, perConsortium to Inform Molecular and Practical Approaches to Central Nervous SystemTumor 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 wholechromosome 10 loss, or Telomerase reverse transcriptase (TERT) promoter mutation.
Patients for which bevacizumab or lomustine are reasonable systemic treatmentsfollowing surgery.
Eligible patients must be experiencing a known or suspected first recurrence of asupratentorial GBM following prior first-line concurrent TMZ and RT (allowedhypofractionation of prior RT dose ≥ 40 Gray [Gy] of a planned 60 Gy dose) and atleast one cycle of adjuvant TMZ. RT must have concluded >45 days prior toenrollment, and most recent adjuvant TMZ treatment(s) must have been concluded orterminated >10 days prior to enrollment. Prior adjuvant TMZ cycles up to 12, prioradjuvant tumor-treating fields (TTF), and prior External Beam Radiotherapy (EBRT)doses via proton or photon treatments up to 72 Gy equivalent are allowed. Note: Thisincludes 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 moreaxial slices 5 mm apart.
The pre-operative tumor (including enhanced and unenhanced tumor) planned forresection that is 60 mm2 or less in maximum cross section.
Tumor that in the opinion of the enrolling neurosurgeon is amenable toattempted gross total resection (GTR). Prior diagnostic biopsy allowed.
Anticipated GammaTile placement (i.e., closest aspect of post resection tumorbed that is anticipated to receive GammaTile placement) that is > 15mm from theoptic chiasm or brainstem.
Multifocal enhancing disease is allowed if it can be fully encompassed in oneoperative bed while meeting criterion a-e.
Ability to complete an MRI of the head with and without contrast, and a non-contrastCT.
All subjects fluent in English will complete neurocognitive evaluations. Patientsnot fluent in English are allowed on trial but will not take neurocognitive tests ascomparative 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 ofroutinely used methods for MGMT methylation testing (e.g., mutagenically separatedpolymerase 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 priorstudy.
Suspicion of suspected tumor recurrence is on imaging and/or histologic grounds. Ifimaging, 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 thanthose 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 thescreening MRI. Utilization of the lowest useful dose and shortest useful course areencouraged.
Karnofsky Performance Scale (KPS) score of ≥ 70 documented within ± 21 days ofsigning consent.
Eastern Cooperative Oncology Group Performance Score (ECOG-PS) of <2 documented ≤ 21days 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 ULNmay 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 investigatorimmediately if they become pregnant at any time during the trial period. They mustbe willing to use a form of contraception to prevent pregnancy during treatment.
Willingness and ability to provide written informed consent or have their legallyauthorized representative provide consent and Health Insurance Portability andAccountability (HIPAA) authorization for them if they physically are unable to signprior to performance of any study-related procedure.
Availability of prior radiotherapy treatment plan details in Digital Imaging andCommunications in Medicine (DICOM) format is desired but not required for studyparticipation.
Exclusion
Exclusion Criteria:
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 trialeligibility.
Known germline DNA repair defect (mismatch repair deficiency, POLE mutation, e.g.).If not previously completed, germline sequencing is not required to determine trialeligibility.
Patients not appropriate for treatment with bevacizumab or lomustine, in the opinionof the investigator or medical team.
Patients for whom any additional treatment is planned in the absence of recurrent orprogressive 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 ofbevacizumab 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 followingcontraindications to the use of bevacizumab, must be absent. (Note: If any of thesecontraindications exist, the use of lomustine must be considered as the systemicagent. If both bevacizumab and lomustine are inappropriate in the treatingphysician's opinion, the patient must be excluded).
Clinically Significant Cardiovascular Disease Defined as follows: Inadequatelycontrolled hypertension (i.e., systolic blood pressure (SBP) > 160 mm Hg and/ordiastolic 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 ofbleeding, i.e., Hereditary Hemorrhagic Telangiectasia Type I or HHT-1) orcoagulopathy in the absence of therapeutic anti-coagulation or anyhemorrhage/bleeding event > Grade 3
- 28 days prior to registration. Note: Patients with full-doseanticoagulants are eligible provided the patient has been on a stable dosefor ≥14 days.
Active wound, a serious or non-healing wound, an active ulcer or untreated bonefracture.
History of abdominal fistula, gastrointestinal perforation, or intra-abdominalabscess ≤ 180 days prior to consenting.
Previous or current treatment with an investigational or FDA approved systemictherapy for glioblastoma other than external beam radiation (proton or photon),temozolomide (Temodar®), or tumor treatment fields (Optune®) (e.g., other forms ofsystemic therapy, targeted therapeutics, immunotherapy).
Sensitivity to bovine (cow) derived materials including collagen products.
Patients with a prior or concurrent malignancy whose natural history or treatmenthas the potential to interfere with the safety or efficacy assessment of theinvestigational 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 ImmunodeficiencyVirus [HIV]) or severe pneumonia.
Major surgical procedure ≤21 days prior to protocol surgery or anticipation of needfor a major surgical procedure during the course of study treatment.
Uncontrolled intercurrent illness including, but not limited to, uncontrolledhypertension (systolic blood pressure >140 mm Hg or diastolic blood pressure >90 mmHg) despite optimal medical management; myocardial infarction less than 6 monthsbefore the planned surgery date; arterial thrombotic or embolic events, such ascerebrovascular accident (including transient ischemic attacks) or pulmonaryembolism 180 days before the planned surgery date, or psychiatric illness/socialsituations that would impair understanding or limit compliance with studyrequirements, including ability to complete neurocognitive assessments and qualityof life questionnaires, and returning for follow-up care
Any concomitant therapy that, in the investigator's opinion, would interfere withthe 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 GBMtreatment, unless they have sufficiently recovered as evidenced by a drop to grade ≤2 or have full resolution.