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

Malignant Glioma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05030298
• Other study ID #: MC210710
• Secondary ID: NCI-2021-0884820
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: May 23, 2023
• Est. completion date: September 15, 2025

Study information

• Verified date: April 2024
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: September 15, 2025
• Est. primary completion date: September 15, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Glioma
• Malignant Glioma

Intervention

Radiation:
• Radiation Therapy
Undergo radiation therapy
• Radiosurgery
Undergo radiosurgery

Procedure:
• Stereotactic Biopsy
Undergo MRI-guided stereotactic biopsy

Drug:
• Temozolomide
Drug

Procedure:
• Therapeutic Conventional Surgery
Undergo surgery
• Tumor Treating Fields Therapy
Undergo TTF
• Magnetic Resonance Imaging
Undergo MRI
• Biospecimen Collection
Undergo blood sample collection
• Biopsy
Undergo biopsy

Locations

Country	Name	City	State
United States	Mayo Clinic in Florida	Jacksonville	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Mayo Clinic

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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