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

Primary Purpose

Malignant Glioma

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Radiation Therapy
Radiosurgery
Stereotactic Biopsy
Temozolomide
Therapeutic Conventional Surgery
Tumor Treating Fields Therapy
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Malignant Glioma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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
  • 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) =< 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 starting treatment)
  • Platelet count >= 80,000/mm^3 (80 x 10^9/L) (obtained =< 14 days prior to starting treatment)
  • Hemoglobin (Hgb) >= 9 g/dL (=< 14 days prior to starting treatment)

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
  • 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
  • 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

Sites / Locations

  • Mayo Clinic in FloridaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Cohort A (stereotactic biopsy, radiosurgery, surgery)

Cohort B (surgery, radiation therapy, chemotherapy)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.

Full Information

First Posted
August 23, 2021
Last Updated
August 11, 2023
Sponsor
Mayo Clinic
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1. Study Identification

Unique Protocol Identification Number
NCT05030298
Brief Title
Preoperative Radiosurgery for the Treatment of High Grade Glioma, The NeoGlioma Study
Official Title
Preoperative Radiosurgery in High Grade Glioma: A Phase I/IIA Clinical Trial: The NeoGlioma Study
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 23, 2023 (Actual)
Primary Completion Date
September 15, 2025 (Anticipated)
Study Completion Date
September 15, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mayo Clinic

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malignant Glioma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cohort A (stereotactic biopsy, radiosurgery, surgery)
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort B (surgery, radiation therapy, chemotherapy)
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Radiation
Intervention Name(s)
Radiation Therapy
Other Intervention Name(s)
Cancer Radiotherapy, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation
Intervention Description
Undergo radiation therapy
Intervention Type
Radiation
Intervention Name(s)
Radiosurgery
Other Intervention Name(s)
Ablation, Radiosurgical, Radiation Surgery
Intervention Description
Undergo radiosurgery
Intervention Type
Procedure
Intervention Name(s)
Stereotactic Biopsy
Intervention Description
Undergo MRI-guided stereotactic biopsy
Intervention Type
Drug
Intervention Name(s)
Temozolomide
Other Intervention Name(s)
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, Methazolastone, RP-46161, SCH 52365, Temcad, Temodal, Temodar, Temomedac, TMZ
Intervention Description
Drug
Intervention Type
Procedure
Intervention Name(s)
Therapeutic Conventional Surgery
Intervention Description
Undergo surgery
Intervention Type
Procedure
Intervention Name(s)
Tumor Treating Fields Therapy
Other Intervention Name(s)
Alternating Electric Field Therapy, TTF, TTFields
Intervention Description
Undergo TTF
Primary Outcome Measure Information:
Title
Proportion of patients experiencing any acute grade 3 or greater unplanned adverse event
Description
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.
Time Frame
Up to 4 weeks postoperative radiotherapy
Secondary Outcome Measure Information:
Title
Acute clinical toxicity
Description
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.
Time Frame
Up to 4 weeks postoperative radiotherapy
Title
Radiographic tumor control
Description
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.
Time Frame
At 12 months post-surgery
Title
Rate of pseudoprogression
Description
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.
Time Frame
At first post radiation scan
Title
Overall survival
Description
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.
Time Frame
At 12 months post-surgery
Other Pre-specified Outcome Measures:
Title
Tumor tissue evaluation of tumor changes
Description
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.
Time Frame
Up to 14 days Post-radiosurgery

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Daniel Trifiletti
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic in Florida
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224-9980
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Clinical Trial Referral Office
Phone
855-776-0015
Email
mayocliniccancerstudies@mayo.edu
First Name & Middle Initial & Last Name & Degree
Daniel Trifiletti, M.D.

12. IPD Sharing Statement

Learn more about this trial

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

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