Preoperative Radiosurgery for the Treatment of High Grade Glioma, NeoGlioma Trial

Official title

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

Overview

This phase I 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.

Detailed description

PRIMARY OBJECTIVE:

I. To evaluate the feasibility, safety and maximum tolerated dose (MTD) 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: This is a dose-escalation study.

Patients undergo magnetic resonance imaging (MRI)-guided stereotactic biopsy. Within 14 days of registration, patients undergo either standard of care surgery or radiosurgery in 1 fraction. Within 14 days, patients who underwent radiosurgery then undergo surgery. Within 4-6 weeks, all 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. Additionally, patients undergo MRI and blood sample collection and optional biopsy throughout the study.

After completion of study treatment, patients are followed up every 2-3 months for 12 months and then every 3 months for up to 3 years after registration.

Interventions

• Radiation Radiation Therapy
  Undergo radiation therapy
• Radiation Radiosurgery
  Undergo radiosurgery
• Procedure Stereotactic Biopsy
  Undergo MRI-guided stereotactic biopsy
• Drug Temozolomide
  Drug
• Procedure Tumor Treating Fields Therapy
  Undergo TTF
• Procedure Magnetic Resonance Imaging
  Undergo MRI
• Procedure Biospecimen Collection
  Undergo blood sample collection
• Procedure Biopsy
  Undergo biopsy
• Procedure Therapeutic Conventional Surgery
  Undergo surgery

Primary outcome measures

• Proportion of patients experiencing any acute grade 3 or greater unplanned adverse event [Time frame: Up to 4 weeks postoperative radiotherapy]
• Acute clinical toxicity [Time frame: Up to 4 weeks postoperative radiotherapy]
• Maximum tolerated dose (MTD) of preoperative radiosurgery [Time frame: Up to 4 weeks postoperative radiotherapy]

Secondary outcome measures (3)

• Radiographic tumor control [Time frame: At 12 months post-surgery]
• Rate of pseudoprogression [Time frame: At first post radiation scan]
• Overall survival [Time frame: At 12 months post-surgery]

Eligibility criteria

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
• 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
• 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. Patients over 50 years of age who decline pregnancy testing are still eligible without a pregnancy test.
• Ability to complete questionnaire(s) by themselves or with assistance
• Provide written informed consent
• Willing to receive adjuvant radiotherapy at enrolling institution at the time of registration
• Willing to provide tissue and/or blood samples for correlative research purposes

Exclusion criteria

• Any of the following:

• Pregnant women
• Nursing women who are unwilling to cease during therapy
• Men or women of childbearing potential who are unwilling to employ adequate contraception
• Prior history of cranial radiotherapy
• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 2 centers

• Mayo Clinic in Arizona — Phoenix
• Mayo Clinic in Florida — Jacksonville

Identifiers

NCT: NCT05030298 · MC210710 · 20-013209

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗