Glioblastoma, Gliosarcoma
Conditions
Brief summary
This pilot clinical trial studies the side effects of spectroscopic magnetic resonance imaging (MRI)-guided radiation therapy and how well it works in treating patients with newly-diagnosed glioblastoma or gliosarcoma. Spectroscopic MRI can show doctors where the extent of tumor is in the brain beyond current clinical MRI scans by mapping areas of high tumor metabolism. Radiation therapy uses high energy beams to kill tumor cells and shrink tumors. Spectroscopic MRI-guided radiation therapy may work better in treating patients with glioblastoma or gliosarcoma.
Detailed description
PRIMARY OBJECTIVES: I. To determine the feasibility of using spectroscopic MRI (sMRI) to guide dose-escalated radiation therapy (RT) for newly-diagnosed glioblastoma (GBM)s. II. To determine the safety of using sMRI to guide dose-escalated RT for newly-diagnosed GBMs. SECONDARY OBJECTIVE: I. To determine whether the progression free survival at 1 year with sMRI-guided, dose-escalated RT is improved for newly-diagnosed GBMs. TERTIARY OBJECTIVES: I. To determine whether sMRI-guided, dose-escalated RT increases the overall survival of patients with newly diagnosed GBMs. II. To determine whether sMRI data obtained after initiation of therapy (at 2 weeks after RT/TMZ start and prior to cycle 1 and 5 of adjuvant temozolomide \[TMZ\]) will provide early evidence of GBM progression not seen on standard MRIs. III. To determine whether performance on neurocognitive and quality-of-life (QOL) assessments in newly-diagnosed GBM patients treated with sMRI-guided, dose-escalated RT differ from historical controls. OUTLINE: Patients undergo sMRI-guided radiation therapy daily for the first 5 days of every week (Monday - Friday) over 6 weeks. Patients also receive standard of care temozolomide orally (PO) daily during radiation therapy for up to 42 days. After completion of study treatment, patients are followed up every 3 months for up to 2 years and then periodically.
Interventions
RADIATIONDose-Escalated Radiation Therapy
Undergo sMRI-guided radiation therapy, dose painted to maximum of 75 Gy over six weeks
PROCEDURESpectroscopic Magnetic Resonance Imaging
Patients will undergo sMRI scans within a 14 day window prior to starting treatment
DRUGTemozolomide
Given PO
Sponsors
Johns Hopkins University
University of Miami
National Cancer Institute (NCI)
National Institutes of Health (NIH)
Emory University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must have a newly-diagnosed glioblastoma or gliosarcoma that has been confirmed pathologically by a board-certified neuropathologist * Patients must be able to have MRI scans * Patients must have the following lab values ≤ 14 days prior to registration: * White blood cell (WBC) ≥ 3,000/µL * Absolute neutrophil count (ANC) ≥ 1,500/µL * Platelet count of ≥ 75,000/µL * Hemoglobin ≥ 9.0 gm/dL (transfusion is allowed to reach minimum level) * Serum glutamic-oxaloacetic transaminase (SGOT) ≤ 2.0 x upper limit of normal (ULN) * Bilirubin ≤ 2 x ULN * Creatinine ≤ 1.5 mg/dL * Patients must have a life expectancy of ≥ 12 weeks * Patients must have a Karnofsky performance status (KPS) ≥ 60 * Patients who are women of childbearing potential must have a negative pregnancy test documented ≤ 14 days prior to registration; this is not specific to dose escalation and is mandatory for standard care for patients being treated with radiation therapy; the cost of this test will be covered by standard of care * Patients must be able to understand and provide written informed consent * Members of all races and ethnic groups are eligible for this trial; subjects will be approximately representative of the demographics of the referral base for the participating institutions * Patient must be able to swallow capsules * Patients must be willing to forego other cytotoxic and non-cytotoxic therapies against the tumor while being treated on this protocol
Exclusion criteria
* Patients with pacemakers, aneurysm clips, neurostimulators, cochlear implants, metal in ocular structures, history of being a steel worker, or other incompatible implants which makes MRI safety an issue are excluded * Patients that have any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy are excluded * Patients with a history of any other invasive cancer (except non-melanoma skin cancer and excluding carcinoma in-situ), unless in complete remission and off of all therapy for that disease for ≥ 3 years, are ineligible * Patients with an active infection or serious intercurrent medical illness are ineligible * Patients receiving any other investigational agents are excluded * Patients who have received prior cytotoxic, non-cytotoxic or experimental drug therapies for brain tumor are excluded * Patients with a history of prior cranial radiation are ineligible * Patients may not be enrolled on any other therapeutic trial for which they are receiving an anti-tumor therapy * Patients with GBMs located in the following anatomical regions known to have magnetic susceptibility or poor signal will be excluded: mesial temporal lobe, orbitofrontal cortex, prefrontal cortex, medial frontal gyrus, brainstem, and cerebellum * The maximum radiation target volume for gross tumor volume 3 (GTV3) is 65 cc (per NRG Oncology guide); patient may be excluded after the first sMRI scan if the GTV3 volume is greater than 65 cc (we anticipate that contrast-enhancing tumor volume \[residual tumor volume following tumor resection\] would be less than 20 cc)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility as Assessed by Successful Co-registration of sMRI-based Treatment Volumes With Clinical Images Into the Radiation Treatment Execution Platform | Up to 2 years after completion of therapy | Feasibility of this approach will be determined by whether treatment volumes based on sMRI can be co-registered with clinical images and transferred into the radiation treatment execution platform in a seamless manner, so that sMRI information can be efficiently applied to the patient treatment. |
| Incidence of Adverse Event Assessed by Common Terminology Criteria for Adverse Events Version 4.0 | Up to 2 years after completion of therapy | The safety of sMRI to guide dose-escalated RT will be confirmed by assessing toxicity potentially attributable to the RT. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | 2 years from the start of RT. | Patients were followed at least every 3 months for 2 years from the start of RT. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | 2.5 years from start of RT | Patients were followed at least every 3 months for 2.5 years from the start of RT. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| sMRI-Guided RT With TMZ Patients undergo spectroscopic magnetic resonance imaging-guided dose-escalated radiation therapy daily for the first 5 days of every week (Monday - Friday) over 6 weeks. Patients also receive standard of care temozolomide PO daily during radiation therapy for up to 42 days.
Dose-Escalated Radiation Therapy: Undergo sMRI-guided radiation therapy, dose painted to maximum of 75 Gy over six weeks
Spectroscopic Magnetic Resonance Imaging: Patients will undergo sMRI scans within a 14 day window prior to starting treatment
Temozolomide: Given PO | 30 |
| Total | 30 |
Baseline characteristics
| Characteristic | sMRI-Guided RT With TMZ |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 7 Participants |
| Age, Categorical Between 18 and 65 years | 23 Participants |
| Age, Continuous | 56.4 Years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 28 Participants |
| Region of Enrollment United States | 30 Participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 16 / 30 |
| other Total, other adverse events | 30 / 30 |
| serious Total, serious adverse events | 14 / 30 |
Outcome results
Primary
Feasibility as Assessed by Successful Co-registration of sMRI-based Treatment Volumes With Clinical Images Into the Radiation Treatment Execution Platform
Feasibility of this approach will be determined by whether treatment volumes based on sMRI can be co-registered with clinical images and transferred into the radiation treatment execution platform in a seamless manner, so that sMRI information can be efficiently applied to the patient treatment.
Time frame: Up to 2 years after completion of therapy
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| sMRI-Guided RT With TMZ | Feasibility as Assessed by Successful Co-registration of sMRI-based Treatment Volumes With Clinical Images Into the Radiation Treatment Execution Platform | 30 Participants |
Primary
Incidence of Adverse Event Assessed by Common Terminology Criteria for Adverse Events Version 4.0
The safety of sMRI to guide dose-escalated RT will be confirmed by assessing toxicity potentially attributable to the RT.
Time frame: Up to 2 years after completion of therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| sMRI-Guided RT With TMZ | Incidence of Adverse Event Assessed by Common Terminology Criteria for Adverse Events Version 4.0 | 79 Adverse Events |
Secondary
Progression Free Survival (PFS)
Patients were followed at least every 3 months for 2 years from the start of RT.
Time frame: 2 years from the start of RT.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| sMRI-Guided RT With TMZ | Progression Free Survival (PFS) | 16.6 Months |
Other Pre-specified
Overall Survival (OS)
Patients were followed at least every 3 months for 2.5 years from the start of RT.
Time frame: 2.5 years from start of RT
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| sMRI-Guided RT With TMZ | Overall Survival (OS) | 23 Months |