Preoperative Radiosurgery for the Treatment of High Grade Glioma, The NeoGlioma Study

Preoperative Radiosurgery in High Grade Glioma: A Phase I/IIA Clinical Trial: The NeoGlioma Study

This phase I/IIA trial finds out the possible benefits and/or side effects of radiosurgery before surgery (preoperative) in treating patients with high grade glioma. Radiosurgery uses special equipment to position the patient and precisely give a single large dose of radiation to the tumor. This method may kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Giving pre-operative radiosurgery may improve the odds of brain tumor control and reduce treatment-related side effects.

Study Overview

• Status: Recruiting
• Conditions: Malignant Glioma
• Intervention / Treatment: Procedure: Magnetic Resonance Imaging; Procedure: Biospecimen Collection; Procedure: Therapeutic Conventional Surgery; Radiation: Radiation Therapy; Procedure: Biopsy; Drug: Temozolomide; Radiation: Radiosurgery; Procedure: Stereotactic Biopsy; Procedure: Tumor Treating Fields Therapy

Detailed Description

PRIMARY OBJECTIVE:

I. To evaluate the safety of preoperative radiosurgery in the treatment of patients with biopsy-proven high grade glioma prior to conventional therapy.

SECONDARY OBJECTIVES:

I. Acute clinical toxicity profile using Common Terminology Criteria for Adverse Events (CTCAE) version 5 (defined as within 4 weeks of completion of postoperative radiotherapy.

II. Radiographic tumor control at 12 months following surgery (per Response Assessment in Neuro-Oncology [RANO] criteria).

III. Rate of pseudoprogression at first post radiation scan (RANO criteria). IV. Overall survival at 12 months following surgery.

CORRELATIVE RESEARCH OBJECTIVE:

I. Evaluation of the tumor repair pathways triggered by radiation, tumor vascular changes, tumor microenvironment immune profiling, cell cultures, and the creation of orthotopic xenograft models for future study.

OUTLINE: Patients are assigned to 1 of 2 cohorts.

COHORT A: Patients undergo magnetic resonance imaging (MRI)-guided stereotactic biopsy. Patients then undergo radiosurgery over 1 fraction. Within 14 days, patients undergo surgery. Within 4-6 weeks, patients then receive standard of care radiation therapy over 30 fraction and temozolomide daily with or without tumor treating fields (TTF) at the discretion of the treating neuro-oncologist.

COHORT B: Patients undergo surgery. Within 4-6 weeks, patients then receive standard of care radiation therapy over 30 fraction and temozolomide daily with or without TTF at the discretion of the treating neuro-oncologist.

Additionally, patients undergo MRI and blood sample collection and optional biopsy on study.

After completion of study treatment, patients are followed up every 2-3 months for up to 5 years.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Jacksonville, Florida, United States, 32224-9980
      • Recruiting
      • Mayo Clinic in Florida
      • Contact: Clinical Trial Referral Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu
      • Principal Investigator: Daniel M. Trifiletti, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age >= 18 years
• Clear clinical and radiographic evidence of primary high grade glioma (HGG) as judged by the Mayo multidisciplinary neuro-oncology team (World Health Organization [WHO] grade III-IV, including glioblastoma) regardless of IDH and MGMT status
• Patients who underwent a previous biopsy confirming high grade glioma are eligible for enrollment to either cohort if a further resection is planned
• Planned neurosurgical resection of tumor
• Judged to not be at risk of significant clinical risk (i.e. herniation) with radiation-induced edema prior to resection
• No prior history of cranial radiotherapy
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
• Negative pregnancy test done =< 14 days prior to registration, for women of childbearing potential only
• Ability to complete questionnaire(s) by themselves or with assistance
• Provide written informed consent
• Planning to receive adjuvant radiotherapy at enrolling institution
• Willing to provide tissue and/or blood samples for correlative research purposes
• Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (obtained =< 14 days prior to registration)
• Platelet count >= 80,000/mm^3 (80 x 10^9/L) (obtained =< 14 days prior to registration)
• Hemoglobin (Hgb) >= 9 g/dL (=< 14 days prior to registration)

Exclusion Criteria:

• Any of the following:

  • Pregnant women
  • Nursing women
  • Men or women of childbearing potential who are unwilling to employ adequate contraception
• Unwillingness to participate in study
• Investigator discretion that enrollment on the study would pose undo harm or risk to the patient
• Non-MRI compatible implanted medical device
• Use of systemic anti-cancer therapy within the previous 3 months
• Medical contraindication to craniotomy and tumor resection

• Pathologic confirmation of grade I-II glioma, brain metastasis, or other brain tumor

  • Note: Patients with a history of grade I-II glioma are eligible if they have only received surgery as treatment and now there is concern for transformation to grade III-IV tumor
• Primary spinal cord glioma or primary brainstem glioma
• Residual tumor of excessive volume or eloquent location per investigator discretion
• Patients who are unwilling or unable to comply with study procedures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A (stereotactic biopsy, radiosurgery, surgery); Patients undergo MRI-guided stereotactic biopsy. Patients then undergo radiosurgery over 1 fraction. Within 14 days, patients undergo surgery. Within 4-6 weeks, patients then receive standard of care radiation therapy over 30 fraction and temozolomide daily with or without TTF at the discretion of the treating neuro-oncologist. Additionally, patients undergo MRI and blood sample collection and optional biopsy on study.	Procedure: Magnetic Resonance Imaging; Undergo MRI; Other Names: MRI; Magnetic Resonance; Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR; MR Imaging; MRI Scan; NMR Imaging; NMRI; nuclear magnetic resonance imaging; Magnetic Resonance Imaging (MRI); sMRI; Magnetic resonance imaging (procedure); MRIs; Structural MRI; Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Procedure: Therapeutic Conventional Surgery; Undergo surgery; Radiation: Radiation Therapy; Undergo radiation therapy; Other Names: Cancer Radiotherapy; ENERGY_TYPE; Irradiate; Irradiated; Irradiation; Radiation; Radiation Therapy, NOS; Radiotherapeutics; Radiotherapy; RT; Therapy, Radiation; Procedure: Biopsy; Undergo biopsy; Other Names: Bx; BIOPSY_TYPE; Drug: Temozolomide; Drug; Other Names: Temodar; SCH 52365; Temodal; Temcad; Methazolastone; RP-46161; Temomedac; TMZ; CCRG-81045; Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-; M & B 39831; M and B 39831; Gliotem; Temizole; Radiation: Radiosurgery; Undergo radiosurgery; Other Names: Ablation, Radiosurgical; Radiation Surgery; Procedure: Stereotactic Biopsy; Undergo MRI-guided stereotactic biopsy; Procedure: Tumor Treating Fields Therapy; Undergo TTF; Other Names: TTFields; Alternating Electric Field Therapy; TTF
Active Comparator: Cohort B (surgery, radiation therapy, chemotherapy); Patients undergo surgery. Within 4-6 weeks, patients then receive standard of care radiation therapy over 30 fraction and temozolomide daily with or without TTF at the discretion of the treating neuro-oncologist. Additionally, patients undergo MRI and blood sample collection and optional biopsy on study.	Procedure: Magnetic Resonance Imaging; Undergo MRI; Other Names: MRI; Magnetic Resonance; Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR; MR Imaging; MRI Scan; NMR Imaging; NMRI; nuclear magnetic resonance imaging; Magnetic Resonance Imaging (MRI); sMRI; Magnetic resonance imaging (procedure); MRIs; Structural MRI; Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Procedure: Therapeutic Conventional Surgery; Undergo surgery; Radiation: Radiation Therapy; Undergo radiation therapy; Other Names: Cancer Radiotherapy; ENERGY_TYPE; Irradiate; Irradiated; Irradiation; Radiation; Radiation Therapy, NOS; Radiotherapeutics; Radiotherapy; RT; Therapy, Radiation; Procedure: Biopsy; Undergo biopsy; Other Names: Bx; BIOPSY_TYPE; Drug: Temozolomide; Drug; Other Names: Temodar; SCH 52365; Temodal; Temcad; Methazolastone; RP-46161; Temomedac; TMZ; CCRG-81045; Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-; M & B 39831; M and B 39831; Gliotem; Temizole; Procedure: Tumor Treating Fields Therapy; Undergo TTF; Other Names: TTFields; Alternating Electric Field Therapy; TTF

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients experiencing any acute grade 3 or greater unplanned adverse event	Assessed per Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0. The toxicity rate will be estimated using a binomial estimator and a one-sided 95% confidence interval (CI) of the rate will be computed with normal approximation.	Up to 4 weeks postoperative radiotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute clinical toxicity	Assessed per CTCAE v5.0. The maximum grade for each type of acute adverse events will be recorded for each patient. Data will be summarized as frequencies and relative frequencies by treatment arm. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration. Rates will be compared between arms using chi-squared tests.	Up to 4 weeks postoperative radiotherapy
Radiographic tumor control	Assessed per Response Assessment in Neuro-Oncology (RANO) criteria. The cumulative incidence of radiographic tumor recurrence will be estimated using a competing risks method (Gooley et al.) by treatment arm. The competing risks will be death. Comparison between arms will employ Fine-Gray regression.	At 12 months post-surgery
Rate of pseudoprogression	Assessed per RANO criteria. Data will be summarized as frequencies and relative frequencies by treatment arm. Additionally, the relationship of the pseudoprogression(s) to the study treatment will be taken into consideration. Rates will be compared between arms using chi-squared tests.	At first post radiation scan
Overall survival	Will be estimated with a Kaplan-Meier estimator and curve by treatment arm. Estimates will be given for specific time points along with 95% CIs. Comparison between arms will employ a log-rank test.	At 12 months post-surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor tissue evaluation of tumor changes	Any excess tissue recovered from the surgical specimen (after standard of care pathologic evaluation) will undergo a series of advanced testing, potentially including but not limited to evaluation of the tumor repair pathways triggered by radiation, tumor vascular changes, tumor microenvironment immune profiling, cell cultures, and the creation of orthotopic xenograft models for future study. Analysis will be completed outside the scope of this protocol.	Up to 14 days Post-radiosurgery

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Daniel M. Trifiletti, M.D., Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): May 23, 2023
• Primary Completion (Estimated): September 15, 2025
• Study Completion (Estimated): September 15, 2025

Study Registration Dates

• First Submitted: August 23, 2021
• First Submitted That Met QC Criteria: August 26, 2021
• First Posted (Actual): September 1, 2021

Study Record Updates

• Last Update Posted (Actual): April 5, 2024
• Last Update Submitted That Met QC Criteria: April 4, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Temozolomide
• Other Study ID Numbers: MC210710; 20-013209 (Other Identifier: Mayo Clinic Institutional Review Board); NCI-2021-08848 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No