A Study to Evaluate Vascular Normalization in Patients With Recurrent Glioblastoma Treated With Bevacizumab Using FMISO PET and Vascular MRI
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 11
- 试验地点
- 1
- 主要终点
- Change in Tumor Blood Flow/Perfusion
研究概览
简要总结
In this research study, the investigators are using FMISO-PET and MRI scans to explore the delivery of bevacizumab to the blood vessels in patient's with recurrent glioblastoma before and after treatment.
Bevacizumab is approved by the U.S. Food and Drug Administration for use in patients with recurrent glioblastoma . It works by targeting a specific protein called VEGF, which plays a role in promoting the growth or spreading of tumor blood vessels. Since anti-VEGF agents also affect normal blood vessels in the brain, they can inhibit the way other drugs used in combination with bevacizumab are delivered to the tumor.
In PET scans, a radioactive substance is injected into the body. The scanning machine finds the radioactive substance, which tends to go to cancer cells. For the PET scans in this research study, the investigators are using an investigational radioactive substance called FMISO. "Investigational" means that the role of FMISO-PET scans is still being studied and that research doctors are trying to find out more about it. FMISO goes to areas with low oxygenation so parts of the tumor that do not have enough oxygen can be seen.
In addition, a vascular MRI will be used to evaluate the changes in tumor blood flow, blood volume, and how receptive blood vessels are. This scan will be performed at the same time of the FMISO-PET scan.
详细描述
This study does not add any additional treatment to patients with malignant glioma who are already scheduled to receive bevacizumab monotherapy. All treatment decisions will be at the discretion of the treating physician. There will be no change in the diagnosis or management of the patient based on any procedures or tests carried out as a part of this study.
If the participant chooses to take part in this research study each treatment cycle will last 28 days.
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Day 1-The participant will have the following procedures done before they can receive bevacizumab:
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An assessment of the participant's tumor by Vascular MRI (Magnetic Resonance Imaging) and FMISO-PET scans
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Blood pregnancy test for women of childbearing potential.
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Day 14:The participant will have the following procedures done after they receive bevacizumab:
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An assessment of the participant's tumor by Vascular MRI (Magnetic Resonance Imaging) and FMISO-PET scans before the participant have received bevacizumab
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Blood pregnancy test for women of childbearing potential.
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Day 28: The participant will have the following procedures done after they receive bevacizumab:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Participants must have histologically confirmed glioblastoma and evidence of recurrence. Patients with low-grade tumors who have progressed to glioblastoma are eligible.
- •Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 10 mm. See section 10 for the evaluation of measureable disease.
- •Only patients for whom their neuro-oncologist has planned to give bevacizumab as monotherapy are eligible for this study
- •Age > 18 years. Because no dosing or adverse event data are currently available on the use of FMISO in participants <18 years of age, children are excluded from this study but will be eligible for future pediatric trials.
- •Life expectancy of greater than 3 months.
- •Karnofsky performance status > 60 (see Appendix A).
- •Participants must have normal organ and marrow function as defined below:
- •Leukocytes > 3,000/mcL
- •Absolute neutrophil count > 1,500/mcL
- •Platelets > 100,000/mcL
- •Total bilirubin within normal institutional limits
- •AST (SGOT)/ALT (SGPT) < 2.5 X institutional upper limit of normal
- •Creatinine within normal institutional limits or creatinine clearance > 60 mL/min/1.73 m2 for subjects with creatinine levels about institutional normal.
- •Patient must be able to undergo MRI and PET scans.
- •Patients must be maintained on a stable corticosteroid regimen for 5 days prior each MR-PET scan.
- •The effects of FMISO on the developing human fetus are unknown. For this reason and because radiopharmaceuticals agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- •Ability to understand and the willingness to sign a written informed consent document.
排除标准
- •Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study.
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to temozolomide or FMISO.
- •Participants who have already received anti-VEGF or experimental anti-angiogenic therapy for glioblastoma.
- •Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Pregnant women are excluded from this study because FMISO is a radiopharmaceutical agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with radiopharmaceutical agents, breastfeeding should be discontinued if the mother is treated with radiopharmaceutical agents. These potential risks may also apply to other agents used in this study.
- •HIV-positive individuals on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with FMISO. In addition, these individuals are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated.
- •Patients who are no suitable to undergo MRI or use gadolinium contrast due to:
- •Claustrophobia
- •Presence of metallic objects or implanted medical devices in body (i.e. cardiac pacemaker, aneurysm clips, surgical clips, prostheses, artificial hearts, valves with steel parts, metal fragments, shrapnel, tattoos near the eye, or steel implants)
- •Sickle cell disease
- •Renal failure
- •Reduced renal function, as determined by creatinine clearance < 30 mL/min based on a serum creatinine level obtained within 28 days prior to registration
研究组 & 干预措施
FMISO PET & MRI Group 1
- Bevacizumab:
-- Bevacizumab will be administered at a dose of 10 mg/kg i.v. every 14 days per standard of care and the drug label. A cycle is defined as 28 days (1 month).
-
FMISO PET Scan
-
FMISO will be intravenously injected at a dose of 3.7 MBq/kg (0.1 mCi/kg) (maximum 260 MBq, 7 mCi) in < 15 mL. The IV will remain in place for injection of the gadolinium for the MRI scan. There will be one injection of FMISO in the PET protocol. Approximately 90 minutes after the injection, the PET scan will begin.
-
The PET scan will be approximately 60-75 minutes.
-
MRI -- Each MRI will last 60-75 minutes versus 45 minutes for standard brain MRIs.
干预措施: FMISO PET (Device)
FMISO PET & MRI Group 1
- Bevacizumab:
-- Bevacizumab will be administered at a dose of 10 mg/kg i.v. every 14 days per standard of care and the drug label. A cycle is defined as 28 days (1 month).
-
FMISO PET Scan
-
FMISO will be intravenously injected at a dose of 3.7 MBq/kg (0.1 mCi/kg) (maximum 260 MBq, 7 mCi) in < 15 mL. The IV will remain in place for injection of the gadolinium for the MRI scan. There will be one injection of FMISO in the PET protocol. Approximately 90 minutes after the injection, the PET scan will begin.
-
The PET scan will be approximately 60-75 minutes.
-
MRI -- Each MRI will last 60-75 minutes versus 45 minutes for standard brain MRIs.
干预措施: MRI (Device)
FMISO PET & MRI Group 1
- Bevacizumab:
-- Bevacizumab will be administered at a dose of 10 mg/kg i.v. every 14 days per standard of care and the drug label. A cycle is defined as 28 days (1 month).
-
FMISO PET Scan
-
FMISO will be intravenously injected at a dose of 3.7 MBq/kg (0.1 mCi/kg) (maximum 260 MBq, 7 mCi) in < 15 mL. The IV will remain in place for injection of the gadolinium for the MRI scan. There will be one injection of FMISO in the PET protocol. Approximately 90 minutes after the injection, the PET scan will begin.
-
The PET scan will be approximately 60-75 minutes.
-
MRI -- Each MRI will last 60-75 minutes versus 45 minutes for standard brain MRIs.
干预措施: Bevacizumab (Drug)
FMISO PET & MRI Group 2
Bevacizumab + CCNU:
- Bevacizumab will be administered at a dose of 10 mg/kg i.v. every 14 days per standard of care and the drug label. A cycle is defined as 28 days (1 month).
- CCNU will be administered at a dose of 110 mg/m2 every 42 days per standard of care and the drug label. A cycle is defined as 28 days (1 month).
-FMISO PET Scan
- FMISO will be intravenously injected at a dose of 3.7 MBq/kg (0.1 mCi/kg) (maximum 260 MBq, 7 mCi) in < 15 mL. The IV will remain in place for injection of the gadolinium for the MRI scan. There will be one injection of FMISO in the PET protocol. Approximately 90 minutes after the injection, the PET scan will begin.
- The PET scan will be approximately 60-75 minutes.
- MRI
- Each MRI will last 60-75 minutes versus 45 minutes for standard brain MRIs.
干预措施: FMISO PET (Device)
FMISO PET & MRI Group 2
Bevacizumab + CCNU:
- Bevacizumab will be administered at a dose of 10 mg/kg i.v. every 14 days per standard of care and the drug label. A cycle is defined as 28 days (1 month).
- CCNU will be administered at a dose of 110 mg/m2 every 42 days per standard of care and the drug label. A cycle is defined as 28 days (1 month).
-FMISO PET Scan
- FMISO will be intravenously injected at a dose of 3.7 MBq/kg (0.1 mCi/kg) (maximum 260 MBq, 7 mCi) in < 15 mL. The IV will remain in place for injection of the gadolinium for the MRI scan. There will be one injection of FMISO in the PET protocol. Approximately 90 minutes after the injection, the PET scan will begin.
- The PET scan will be approximately 60-75 minutes.
- MRI
- Each MRI will last 60-75 minutes versus 45 minutes for standard brain MRIs.
干预措施: MRI (Device)
FMISO PET & MRI Group 2
Bevacizumab + CCNU:
- Bevacizumab will be administered at a dose of 10 mg/kg i.v. every 14 days per standard of care and the drug label. A cycle is defined as 28 days (1 month).
- CCNU will be administered at a dose of 110 mg/m2 every 42 days per standard of care and the drug label. A cycle is defined as 28 days (1 month).
-FMISO PET Scan
- FMISO will be intravenously injected at a dose of 3.7 MBq/kg (0.1 mCi/kg) (maximum 260 MBq, 7 mCi) in < 15 mL. The IV will remain in place for injection of the gadolinium for the MRI scan. There will be one injection of FMISO in the PET protocol. Approximately 90 minutes after the injection, the PET scan will begin.
- The PET scan will be approximately 60-75 minutes.
- MRI
- Each MRI will last 60-75 minutes versus 45 minutes for standard brain MRIs.
干预措施: Bevacizumab (Drug)
FMISO PET & MRI Group 2
Bevacizumab + CCNU:
- Bevacizumab will be administered at a dose of 10 mg/kg i.v. every 14 days per standard of care and the drug label. A cycle is defined as 28 days (1 month).
- CCNU will be administered at a dose of 110 mg/m2 every 42 days per standard of care and the drug label. A cycle is defined as 28 days (1 month).
-FMISO PET Scan
- FMISO will be intravenously injected at a dose of 3.7 MBq/kg (0.1 mCi/kg) (maximum 260 MBq, 7 mCi) in < 15 mL. The IV will remain in place for injection of the gadolinium for the MRI scan. There will be one injection of FMISO in the PET protocol. Approximately 90 minutes after the injection, the PET scan will begin.
- The PET scan will be approximately 60-75 minutes.
- MRI
- Each MRI will last 60-75 minutes versus 45 minutes for standard brain MRIs.
干预措施: CCNU (Drug)
结局指标
主要结局
Change in Tumor Blood Flow/Perfusion
时间窗: Baseline and day 14 scans
In this research study, the investigators are using FMISO-PET and MRI scans to explore the delivery of bevacizumab to the blood vessels in patient's with recurrent glioblastoma before and after treatment.
Change in Tumor Hypoxic Volume
时间窗: Baseline and day 14 scans
In this research study, the investigators are using FMISO-PET and MRI scans to explore the delivery of bevacizumab to the blood vessels in patient's with recurrent glioblastoma before and after treatment. Regional hypoxic volume (HV) was determined by thresholding the ratio of the standardized uptake values (SUV) of FMISO in the brain to cerebellum above 1.2. Since some patients had multiple tumors, we identified the HV region within the union of each contrast enhancing region of interest (ROI) and its surrounding FLAIR ROI, so individual tumors could be evaluated separately. HV represents the magnitude of hypoxia within each tumor.
次要结局
- Blood Vessel Permeability (Ktrans Change on MRI Scan)(Baseline and day 14)
- Tumor Blood Flow Measured by MRI Perfusion(Baseline and day 14 scans)
研究者
Elizabeth R. Gerstner, MD
Principal Investigator
Massachusetts General Hospital