FMISO PET Study of Glioblastoma

NCT02076152 | Completed Results DMC

• 2 other identifiers: 13-482R01CA129371
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Recurrent Glioblastoma

Keywords

Recurrent Glioblastoma

Outcome Measures

Primary Outcomes (2)

• Change in Tumor Blood Flow/Perfusion

  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.

  Baseline and day 14 scans

• Change in Tumor Hypoxic Volume

  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.

  Baseline and day 14 scans

Secondary Outcomes (2)

• Blood Vessel Permeability (Ktrans Change on MRI Scan)

  Baseline and day 14

• Tumor Blood Flow Measured by MRI Perfusion

  Baseline and day 14 scans

Study Arms (2)

FMISO PET & MRI Group 1

EXPERIMENTAL

* 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.

Device: FMISO PET; Device: MRI; Drug: Bevacizumab

FMISO PET & MRI Group 2

EXPERIMENTAL

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.

Device: FMISO PET; Device: MRI; Drug: Bevacizumab; Drug: CCNU

Interventions

FMISO PET DEVICE

FMISO PET & MRI Group 1; FMISO PET & MRI Group 2

MRI DEVICE

MR scans will be performed with the same sequences and in the same order during each visit, including T1- and T2-weighted volumetric images, fluid attenuated inversion recovery (FLAIR), contrast agent enhanced T1-weighted permeability, diffusion tensor imaging (DTI), T2/T2\*-weighted perfusion scans, and MR Spectroscopy. The "Autoalign" package available from the manufacturer will be used to achieve the same slice prescription in the same patient at each visit. Each MRI will last 60-75 minutes versus 45 minutes for standard brain MRIs.

FMISO PET & MRI Group 1; FMISO PET & MRI Group 2

Bevacizumab DRUG

A cycle is defined as 28 days (1 month). The study duration is 12 months (12 cycles). Patients will be treated after 12 months or at the time of progression per discretion of their responsible physician.

Also known as: Avastin®

FMISO PET & MRI Group 1; FMISO PET & MRI Group 2

CCNU DRUG

A cycle is defined as 28 days (1 month). The study duration is 12 months (12 cycles). Patients will be treated after 12 months or at the time of progression per discretion of their responsible physician.

FMISO PET & MRI Group 2

Eligibility Criteria

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

You may qualify if:

• 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.

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 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

Sponsors & Collaborators

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

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 01852, United States

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

Bevacizumab; Lomustine

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Nitrosourea Compounds; Urea; Amides; Organic Chemicals; Nitroso Compounds

Results Point of Contact

• Title: Elizabeth Gerstner, MD
• Organization: Massachusetts General Hospital

EGERSTNER@PARTNERS.ORG

617-724-2887

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: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 6, 2014
• First Posted: March 3, 2014
• Study Start: February 1, 2014
• Primary Completion: April 1, 2019
• Study Completion: April 1, 2019
• Last Updated: July 30, 2021
• Results First Posted: July 30, 2021

Record last verified: 2021-07

Locations

US (1)