Bevacizumab w / Temozolomide PET & Vascular MRI For GBM

Completed · Not applicable

Conditions studied: Recurrent Glioblastoma

In brief

This research study is exploring how the blood vessels in the participant's tumor change from treatment with bevacizumab, and how these changes affect the way their tumor absorbs temozolomide (TMZ). The pilot part of this study is to evaluate the use of \[11C\] temozolomide PET (TMZ-PET) scans and MRI scans to tell investigators more about how standard treatment with bevacizumab affects the blood vessels in the participant's tumor, and how these changes affect the way the participant's tumor absorbs temozolomide. "Investigational" means that the role of TMZ-PET scans is still being studied and that research doctors are trying to find out more about it. Bevacizumab is approved by the U.S. Food and Drug Administration for use in people with the participant's type of cancer. It works by blocking signals on a specific protein called vascular endothelial growth hormone (VEGF), which plays a role in promoting the growth of spread of tumor blood vessels. Bevacizumab is an "anti-VEGF' agent because it is designed to slow the growth of the participant's cancer. 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. Researchers are looking for how bevacizumab affects delivery of chemotherapy, in this case temozolomide. 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 a radioactive substance called \[11C\] temozolomide, which is chemically identical to the prescription drug TMZ. TMZ is FDA approved as a chemotherapeutic agent in cancer but \[11C\] temozolomide is an investigational agent. In this research study, participants will receive standard treatment with bevacizumab and oral temozolomide as well as standard MRI scans. In addition, participants will undergo TMZ-PET scans before and after treatment with bevacizumab. The first TMZ-PET scan will occur 7-13 days after starting treatment with oral temozolomide but before beginning treatment with bevacizumab, day 1 after starting treatment with bevacizumab and 1 month after starting bevacizumab. TMZ-PET scans will be given at the same time as a vascular MRI, which will evaluate the changes in tumor blood flow, blood volume, and how receptive blood vessels are while also measuring how much TMZ is in the brain.

Key facts

Study ID

NCT01987830

Run by

Massachusetts General Hospital

People needed

13

Starts

2013-11-01

Expected to finish

2019-04-01

Last updated by the study team

2020-09-04

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Participants must meet the following criteria on screening examination to be eligible to participate in the study:
• Participants must have histologically confirmed glioblastoma and evidence of recurrence > 2 months since last cycle of temozolomide. Patients with low-grade tumors who have progressed to glioblastoma are eligible.
• Patients must have received at least 6 months of monthly temozolomide previously.
• 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 and temozolomide 50mg/m2/day as part of their treatment are eligible for this study
• Age > 18 years. Because no dosing or adverse event data are currently available on the use of radiolabeled temozolomide 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 > 1,000/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 radiolabeled temozolomide 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.

You may not qualify if…

• 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.
• 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 radiolabeled temozolomide 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 radiolabeled temozolomide. 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

Where it is running

• Massachuesett General Hospital — Boston, Massachusetts, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.