Clinical trial NCT05030298: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Malignant Glioma
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2021-09-01
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: The first four patients will be treated by standard of care and all subsequently enrolled patients will undergo preoperative radiosurgery by dose escalation schedule.
Primary purpose: TREATMENT

Brief summary: 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.

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

Primary outcomes:
measure: Proportion of patients experiencing any acute grade 3 or greater unplanned adverse event
timeFrame: Up to 4 weeks postoperative radiotherapy
measure: Acute clinical toxicity
timeFrame: Up to 4 weeks postoperative radiotherapy
measure: Maximum tolerated dose (MTD) of preoperative radiosurgery
timeFrame: Up to 4 weeks postoperative radiotherapy
Secondary outcomes:
measure: Radiographic tumor control
timeFrame: At 12 months post-surgery
measure: Rate of pseudoprogression
timeFrame: At first post radiation scan
measure: Overall survival
timeFrame: At 12 months post-surgery
Other outcomes:
measure: Tumor tissue evaluation of tumor changes
timeFrame: Up to 14 days Post-radiosurgery
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic in Arizona
state: Arizona
city: Jacksonville
country: United States
facility: Mayo Clinic in Florida
state: Florida
Study officials:
affiliation: Mayo Clinic
name: Daniel M. Trifiletti, MD
role: PRINCIPAL_INVESTIGATOR
References: