FMISO PET Study of Glioblastoma

• Status: Completed
• Trial end date: 2019-04-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Massachusetts General Hospital
• Collaborator: National Cancer Institute (NCI)
• Treatments: Bevacizumab

Criteria

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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