Feasibility of [¹⁸F]-Fluoromisonidazole (FMISO) in Assessment of Malignant Brain Tumors
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 77
- 试验地点
- 2
- 主要终点
- Macro-imaging level feasibility
研究概览
简要总结
This phase II trial studies how well 18F- fluoromisonidazole (FMISO) works with positron emission tomography (PET)/magnetic resonance imaging (MRI) in assessing participants with malignant (cancerous) brain tumors. Two contrast agents called gadolinium and ferumoxytol are used during some of the MRI scans. A contrast agent is a liquid-like dye that is given intravenously (IV) to help imaging machines create pictures. The study drug, called FMISO, provides information about the oxygen levels in a tumor, which may affect how the tumor behaves. PET/MRI imaging produces images of the brain and how the body functions. FMISO PET/MRI may help investigators see how much oxygen is getting in the brain tumors.
详细描述
PRIMARY OBJECTIVES:
I. Determine the feasibility of obtaining 18F-fluoromisonidazole (FMISO) PET (hypoxic volume and tumor to blood background values [T/B]) and dynamic susceptibility contrast enhanced (DSC), diffusion-weighted imaging (DWI), & segregation & extravascular localization of ferumoxytol imaging (SELFI) MRI measures in patients with intracranial brain tumors.
II. Determine if MRI contrast-enhancement and hypoxic volume are imaging profiles of glioblastoma immunotherapy-mediated pseudoprogression or true progression in a clinical trial.
III. Determine if SELFI hypoxic fraction are imaging biomarkers of glioblastoma neuroinflammation.
SECONDARY OBJECTIVES:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients (18 years of age and older) with a clinically suspected glioma
- •Able to provide informed written consent and/or acceptable surrogate capable of providing consent on the patient's behalf
- •Legally authorized representative (LAR)-signed informed consent and assent obtained for those subjects identified as decisionally impaired
- •Intracranial disease greater than 5 mL as assessed by T2/fluid attenuated inversion recovery (FLAIR) MR imaging
- •Karnofsky performance score > 60 or Eastern Cooperative Oncology Group (ECOG) < 3 as assessed by referring clinician.
- •Either has previously received therapeutic intervention for an intracranial tumor or is eligible for and agreeable to receiving standard of care stupp protocol radiation and temozolomide after biopsy or maximum safe surgical resection
- •Life expectancy of at least 6 months
- •Female subject of childbearing potential will be asked for possibility of pregnancy. If unsure of pregnancy status, then a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study drug (FMISO). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- •Adequate organ function as demonstrated by a chart review of platelets, renal, hepatic, and coagulation. We will follow the Department of Diagnostic Radiology clinical policy for assessing renal function prior to injecting gadolinium-based contrast. If there is a history of poor kidney function, a point of care serum creatinine test may be performed to ensure adequate kidney function prior to FMISO administration. If there is a history of any other poor organ function, we will not administer Ferumoxytol, but the subject may receive all other study interventions
排除标准
- •Pregnant or breastfeeding.
- •Contraindication to PET, MRI, FMISO, ferumoxytol, or intravenous gadolinium based contrast agents.
- •Claustrophobia is not controlled with medical therapy
- •Weight is greater than modality maximum capacity.
- •Presence of metallic foreign body or implanted medical devices in body not documented as MRI safe according to the Oregon Health & Science University (OHSU) Department of Radiology guidelines (including but not limited to cardiac pacemaker, aneurysm clips, surgical clips, prostheses, artificial hearts, valves with steel parts, metal fragments, shrapnel, tattoos near the eye, or steel implants).
- •Subjects with family history of or known iron overload (genetic hemochromatosis).
- •Subject who have received ferumoxytol within 3 weeks of study entry and require another ferumoxytol administration.
- •Subjects with three or more drug allergies from separate drug classes.
- •History of hypersensitivity allergic reactions attributed to compounds of similar chemical or biologic composition to FMISO. An allergic reaction to nitroimidazoles is highly unlikely.
- •Sickle cell disease.
- •History of hypersensitivity allergic reactions attributed to compounds of similar chemical or biologic composition to ferumoxytol or gadolinium MRI contrast
- •Unsure of pregnancy status as assessed by Department of Radiology and AIRC guidelines.
- •Subjects for whom supplemental oxygen could be harmful such as people with potential for hypoventilation (end-stage chronic obstructive pulmonary disease [COPD], obstructive sleep apnea [OSA] on continuous positive airway pressure [CPAP]/biphasic positive airway pressure [Bi-PAP], etc).
- •Presence of any other co-existing condition that, in the judgment of the principal investigator, might increase the risk to the subject (i.e., plans for hospice or end of life care).
- •Poor peripheral intravenous access evaluated by patient history.
- •Presence of other serious systemic illnesses, including: uncontrolled infection, other uncontrolled malignancy, uncontrolled diabetes type II, or psychiatric/social situations which might impact the endpoint of the study or limit compliance with study requirements.
研究组 & 干预措施
Diagnostic (FMISO, PET/MRI or PET/CT)
Participants receive FMISO and/or FE IV. Patients also undergo dynamic PET/CT or PET/MRI over 120 minutes beginning 1 minute prior to FMISO injection, and static PET/CT or PET/MRI over 20-40 minutes approximately 90 minutes after FMISO injection. Participants may then receive FMISO and/or Fe IV and gadolinium IV and undergo PET/MRI scan, followed by an additional PET/MRI scan without FMISO and/or Fe and gadolinium the following day. These scans may repeat every 4 weeks up to 4 times. Supplemental oxygen may be administered to affect MRI signal change.
干预措施: Oxygen Therapy (Procedure)
Diagnostic (FMISO, PET/MRI or PET/CT)
Participants receive FMISO and/or FE IV. Patients also undergo dynamic PET/CT or PET/MRI over 120 minutes beginning 1 minute prior to FMISO injection, and static PET/CT or PET/MRI over 20-40 minutes approximately 90 minutes after FMISO injection. Participants may then receive FMISO and/or Fe IV and gadolinium IV and undergo PET/MRI scan, followed by an additional PET/MRI scan without FMISO and/or Fe and gadolinium the following day. These scans may repeat every 4 weeks up to 4 times. Supplemental oxygen may be administered to affect MRI signal change.
干预措施: ¹⁸F-Fluoromisonidazole (Drug)
Diagnostic (FMISO, PET/MRI or PET/CT)
Participants receive FMISO and/or FE IV. Patients also undergo dynamic PET/CT or PET/MRI over 120 minutes beginning 1 minute prior to FMISO injection, and static PET/CT or PET/MRI over 20-40 minutes approximately 90 minutes after FMISO injection. Participants may then receive FMISO and/or Fe IV and gadolinium IV and undergo PET/MRI scan, followed by an additional PET/MRI scan without FMISO and/or Fe and gadolinium the following day. These scans may repeat every 4 weeks up to 4 times. Supplemental oxygen may be administered to affect MRI signal change.
干预措施: Computed Tomography (Procedure)
Diagnostic (FMISO, PET/MRI or PET/CT)
Participants receive FMISO and/or FE IV. Patients also undergo dynamic PET/CT or PET/MRI over 120 minutes beginning 1 minute prior to FMISO injection, and static PET/CT or PET/MRI over 20-40 minutes approximately 90 minutes after FMISO injection. Participants may then receive FMISO and/or Fe IV and gadolinium IV and undergo PET/MRI scan, followed by an additional PET/MRI scan without FMISO and/or Fe and gadolinium the following day. These scans may repeat every 4 weeks up to 4 times. Supplemental oxygen may be administered to affect MRI signal change.
干预措施: Magnetic Resonance Imaging (Procedure)
Diagnostic (FMISO, PET/MRI or PET/CT)
Participants receive FMISO and/or FE IV. Patients also undergo dynamic PET/CT or PET/MRI over 120 minutes beginning 1 minute prior to FMISO injection, and static PET/CT or PET/MRI over 20-40 minutes approximately 90 minutes after FMISO injection. Participants may then receive FMISO and/or Fe IV and gadolinium IV and undergo PET/MRI scan, followed by an additional PET/MRI scan without FMISO and/or Fe and gadolinium the following day. These scans may repeat every 4 weeks up to 4 times. Supplemental oxygen may be administered to affect MRI signal change.
干预措施: Positron Emission Tomography (Procedure)
Diagnostic (FMISO, PET/MRI or PET/CT)
Participants receive FMISO and/or FE IV. Patients also undergo dynamic PET/CT or PET/MRI over 120 minutes beginning 1 minute prior to FMISO injection, and static PET/CT or PET/MRI over 20-40 minutes approximately 90 minutes after FMISO injection. Participants may then receive FMISO and/or Fe IV and gadolinium IV and undergo PET/MRI scan, followed by an additional PET/MRI scan without FMISO and/or Fe and gadolinium the following day. These scans may repeat every 4 weeks up to 4 times. Supplemental oxygen may be administered to affect MRI signal change.
干预措施: Gadolinium (Drug)
Diagnostic (FMISO, PET/MRI or PET/CT)
Participants receive FMISO and/or FE IV. Patients also undergo dynamic PET/CT or PET/MRI over 120 minutes beginning 1 minute prior to FMISO injection, and static PET/CT or PET/MRI over 20-40 minutes approximately 90 minutes after FMISO injection. Participants may then receive FMISO and/or Fe IV and gadolinium IV and undergo PET/MRI scan, followed by an additional PET/MRI scan without FMISO and/or Fe and gadolinium the following day. These scans may repeat every 4 weeks up to 4 times. Supplemental oxygen may be administered to affect MRI signal change.
干预措施: Ferumoxytol (Drug)
结局指标
主要结局
Macro-imaging level feasibility
时间窗: One day of diagnostic imaging
Assessed as a factor of generating quantitative positron emission tomography (PET)/magnetic resonance imaging (MRI) metrics (intra-tumoral FMISO tumor to blood \[T/B\] level, hypoxic volume, dynamic susceptibility contrast enhanced \[DSC\], and diffusion-weighted imaging \[DWI\] values, and tissue oxygen maps). Images generated during the administration of oxygen will be used to generate tissue oxygen maps of the brain. Following completion of cohort enrollment, the generation of each quantitative PET/MRI metric will be independently scored as a dichotomous variable; successful or non-successful. Proportional assessment will be performed to assess for project feasibility. The successful generation of PET/MRI metrics in 85% of the initial cohort successfully imaged will need to be achieved for the imaging modality to be deemed feasible for this study. The estimated proportion of success rate for each metric along with the corresponding 95% binomial confidence interval will be provided.
MRI contrast enhancement
时间窗: Up to 5 years
Measured by Response assessment in neuro-oncology criteria sum product diameter assessment. The primary outcomes for this aim are enhancement mismatch ratio and hypoxic volume. Differences in imaging metrics will be evaluated using two sample t-test. If normal assumption is not satisfied, data transformation, or 95% confidence intervals based on bootstrapping method will be used. Exploratory analysis will assess diagnostic performance of imaging metrics (mismatch ratio and hypoxic volume) to identify pseudoprogression at earlier imaging dates.
Successful production of images
时间窗: Two days of diagnostic imaging
Assessed as a factor of generating quantitative positron emission tomography (PET)/magnetic resonance imaging (MRI) metrics (intra-tumoral FMISO tumor to blood \[T/B\] level, hypoxic volume, dynamic susceptibility contrast enhanced \[DSC\], diffusion-weighted imaging \[DWI\], and segregation \& extravascular localization of ferumoxytol imaging \[SELFI\] values, and tissue oxygen maps). Images generated during the administration of oxygen will be used to generate tissue oxygen maps of the brain. Following completion of cohort enrollment, the generation of each quantitative PET/MRI metric will be independently scored as a dichotomous variable; successful or non-successful. Proportional assessment will be performed to assess for project feasibility. The estimated proportion of success rate for each metric along with the corresponding 95% binomial confidence interval will be provided.
SELFI and hypoxic fraction, and T1 ferumoxytol Fe/gadolinium (Gd) log mismatch ratio in patients receiving immunotherapy
时间窗: Two days of diagnostic imaging at time of suspected progression
Diagnostic performance of PET/MRI metrics (SELFI and hypoxic fraction) and Gd\_MRI to differentiate progression from neuroinflammation (pseudoprogresion) will be evaluated using sensitivity, specificity and area under the receiver operating curve (AUROC). Sensitivity and specificity will be characterized using proportions and exact 95% confidence intervals. Difference in diagnostic performance between PET/MRI metrics (SELFI and hypoxic fraction) and Gd\_MRI will be assessed using McNemar's test to compare sensitivity and specificity and using the DeLong test to compare AUROC.
SELFI and hypoxic fraction, and T1 ferumoxytol Fe/gadolinium (Gd) log mismatch ratio in all patients
时间窗: Two days of diagnostic imaging at time of suspected progression
Diagnostic performance of PET/MRI metrics (SELFI and hypoxic fraction) and Gd\_MRI to differentiate progression from neuroinflammation (pseudoprogresion) will be evaluated using sensitivity, specificity and AUROC. Sensitivity and specificity will be characterized using proportions and exact 95% confidence intervals. Difference in diagnostic performance between PET/MRI metrics (SELFI and hypoxic fraction) and Gd\_MRI will be assessed using McNemar's test to compare sensitivity and specificity and using the DeLong test to compare AUROC.
次要结局
- Technical feasibility of PET/MRI(Baseline to the start of long-term follow-up (up to 5 years))
- Successful co-registration (Yes vs. No)(Baseline to the start of long-term follow-up (up to 5 years))
- T/B value and hypoxic tumor volume(Time Frame: Baseline to the start of long-term follow-up (up to 5 years))
- Generation of SELFI Metric(Imaging time points before gadolinium-based contrast agent defined presumed progression, year 1-4)
- SELFI diagnostic performance of imaging metrics(Imaging time points before gadolinium-based contrast agent defined presumed progression, year 1-4)
- Generation of Hypoxic Fraction Metric(Imaging time points before gadolinium-based contrast agent defined presumed progression, year 1-4)
- Hypoxic Fraction Diagnostic performance of imaging metric(Imaging time points before gadolinium-based contrast agent defined presumed progression, year 1-4)
- Hypoxic fraction(Retest will be scheduled within 7 days after the initial PET imaging examination, Baseline, year 1-4])
- SELFI, hypoxic fraction and Modified Response Assessment in Neuro-Oncology (mRANO) criteria(Year 1-5 at suspected disease progression)
- SELFI and hypoxic fraction(Year 1-5 at suspected disease progression)
- Progression free survival (PFS)(Date of diagnosis to date of progression, death or end of study, assessed up to 5 years)
- Overall survival (OS)(Date of diagnosis to date of progression, death or end of study, assessed up to 5 years)
- Change in SELFI and hypoxic fraction(From post-therapy to disease progression/pseudoprogression, year 1-5)
- SELFI(Baseline at year 1-3)
- SELFI and hypoxic fraction(Year 1-4)
研究者
Ramon Barajas
Principal Investigator
OHSU Knight Cancer Institute