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FMISO PET Study of Glioblastoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02076152
Recruitment Status : Completed
First Posted : March 3, 2014
Last Update Posted : April 19, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Elizabeth R. Gerstner, MD, Massachusetts General Hospital

Tracking Information
First Submitted Date  ICMJE February 6, 2014
First Posted Date  ICMJE March 3, 2014
Last Update Posted Date April 19, 2019
Study Start Date  ICMJE February 2014
Actual Primary Completion Date April 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 27, 2017)
  • Change in Tumor blood flow/perfusion [ Time Frame: Baseline and day 14 scans ]
  • Change in tumor hypoxic volume [ Time Frame: Baseline and day 14 scans ]
Original Primary Outcome Measures  ICMJE
 (submitted: February 27, 2014)
Change in hypoxic volume of tumor measured from baseline and day 14 scans [ Time Frame: Baseline and day 14 scans ]
Change History Complete list of historical versions of study NCT02076152 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 27, 2017)
  • Blood vessel permeability (Ktrans change on MRI scan) [ Time Frame: Baseline and day 14 ]
  • Tumor blood flow measured by MRI perfusion [ Time Frame: Baseline and day 14 scans ]
Original Secondary Outcome Measures  ICMJE
 (submitted: February 27, 2014)
Blood vessel permeability (Ktrans change on MRI scan) [ Time Frame: Baseline and day 14 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE FMISO PET Study of Glioblastoma
Official Title  ICMJE A Study to Evaluate Vascular Normalization in Patients With Recurrent Glioblastoma Treated With Bevacizumab Using FMISO PET and Vascular MRI
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.

Detailed Description

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.

  • Day 1-The participant will have the following procedures done before they can receive bevacizumab:

    • An assessment of the participant's tumor by Vascular MRI (Magnetic Resonance Imaging) and FMISO-PET scans
    • Blood pregnancy test for women of childbearing potential.
  • Day 14:The participant will have the following procedures done after they receive bevacizumab:

    • An assessment of the participant's tumor by Vascular MRI (Magnetic Resonance Imaging) and FMISO-PET scans before the participant have received bevacizumab
    • Blood pregnancy test for women of childbearing potential.
  • Day 28: The participant will have the following procedures done after they receive bevacizumab:

    • An assessment of the participant's tumor by Vascular MRI (Magnetic Resonance Imaging) and FMISO-PET scans after the participant has received bevacizumab
    • Blood pregnancy test for women of childbearing potential.

FMISO-PET Scans:

  • The participant will have the scans performed in Charlestown, MA at the Martinos Center. The participant will be injected with two separate intravenous (IV) injections (listed below). Intravenous means a need will be injected into a vein in the participant's arm.

    • FMISO for PET scan and a contrast dye for the MRI scan
    • Drawing blood to assess the radioactivity of FMISO
  • The PET scan will take approximately 60-75 minutes. The participant will receive one injection of FMISO. Following the injection of the radiotracer, blood samples will be taken from the second IV line. The tracer is given through a vein (IV) and travels through the participant's blood and collects in organs and tissues. The participant will need to wait nearby as the tracer is absorbed by the their body. This takes about 90 minutes. Then, the participant will lie on a narrow table that slides into a large tunnel-shaped scanner. The PET will pick up signals from the tracer and a computer will change the signals into 3D pictures that will be displayed on a monitor for the participant's study doctor to read.

MRI Scan:

  • MRI scans will last about 60-75 minutes. This will occur at the same time as the PET scan. The participant will be injected with contrast dye twice during the MRI scan. The participant will have 3 MRI scans (prior to starting treatment, day 1 of treatment and day 14 of treatment) that would not have routinely been performed if the participant were not participating in this study.
  • Blood samples will be collected during both scans in order to measure how the participant blood vessels are processing the radiotracer FMISO and how well it is being delivered to the tumor tissue.
  • The participant will be assessed for side effects via clinic visit or phone call about 24 hours after each of the visits above.

Planned Follow-up: The investigators would like to call the participant every 3 months for three years after the 28 day visit to see how they are doing and if the participant is experiencing any side effects. If the participant is removed from the study due to an unacceptable side effect, the participant will be followed until it has been resolved.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Condition  ICMJE Recurrent Glioblastoma
Intervention  ICMJE
  • Device: FMISO PET
  • Device: MRI
    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.
  • Drug: Bevacizumab
    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.
    Other Name: Avastin®
  • Drug: CCNU
    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.
Study Arms  ICMJE
  • Experimental: 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.
    Interventions:
    • Device: FMISO PET
    • Device: MRI
    • Drug: Bevacizumab
  • Experimental: 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.
    Interventions:
    • Device: FMISO PET
    • Device: MRI
    • Drug: Bevacizumab
    • Drug: CCNU
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 17, 2019)
11
Original Estimated Enrollment  ICMJE
 (submitted: February 27, 2014)
30
Actual Study Completion Date  ICMJE April 2019
Actual Primary Completion Date April 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02076152
Other Study ID Numbers  ICMJE 13-482
R01CA129371 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Elizabeth R. Gerstner, MD, Massachusetts General Hospital
Study Sponsor  ICMJE Massachusetts General Hospital
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Elizabeth Gerstner, MD Massachusetts General Hospital
PRS Account Massachusetts General Hospital
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP