Bevacizumab w / Temozolomide PET & Vascular MRI For GBM

NCT01987830 | Completed Results DMC

• 1 other identifier: 13-322
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Recurrent Glioblastoma

Keywords

Recurrent glioblastoma

Outcome Measures

Primary Outcomes (1)

• Number of Patients With a Decrease in Median Tumor SUV

  Number of patients with a decrease in median tumor standard uptake value (SUV). Median tumor SUV was used as a marker of temozolomide uptake.

  Day 15

Study Arms (1)

TMZ-PET scans/ MRI-PET Scan

OTHER

The investigators plan to study patients with recurrent glioblastoma whose clinical care plan includes treatment with bevacizumab and temozolomide. Patients taking daily temozolomide 50 mg/m2/day will undergo a PET scan using radiolabeled temozolomide (TMZ-PET) at 3 time points: 7-13 days after initiation of temozolomide but before beginning bevacizumab ("baseline"- temozolomide steady-state scan), 1 day after initiation of bevacizumab (day 15) and 1 month after initiation of bevacizumab (day 45). Arterialized venous blood samples will be collected during the imaging in order to measure radioactivity, blood metabolites, and the relationship between radiotracer uptake and tumor features such as blood-brain barrier (BBB) breakdown and tumor blood flow. In addition, we will explore the link between flow, permeability, and tumor temozolomide retention. These studies will be performed using our human simultaneous MRI-PET imaging camera.

Device: MRI-PET; Device: TMZ-PET

Interventions

MRI-PET DEVICE

* \[11C\] temozolomide for PET scan and a contrast dye for the MRI scan * Drawing blood to assess the radioactivity of \[11C\] temozolomide

TMZ-PET scans/ MRI-PET Scan

TMZ-PET DEVICE

The PET scan will take approximately 90 minutes. You will receive one injection of \[11C\] temozolomide. Following the injection of the radioactive substance, blood samples will be taken from the second IV line.

TMZ-PET scans/ MRI-PET Scan

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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 .

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

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Massachuesett General Hospital

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Glioblastoma

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Results Point of Contact

• Title: Dr. Elizabeth Gerstner
• Organization: Massachusetts General Hospital

EGERSTNER@mgh.harvard.edu

(617) 726-2000

Study Officials

• Elizabeth Gerstner, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigators

Study Record Dates

• First Submitted: November 13, 2013
• First Posted: November 19, 2013
• Study Start: November 1, 2013
• Primary Completion: April 1, 2019
• Study Completion: April 1, 2019
• Last Updated: September 4, 2020
• Results First Posted: September 4, 2020

Record last verified: 2020-08

Locations

US (1)