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MRI and PET Scan Using 18F-Fluoromisonidazole In Assessing Tumor Hypoxia in Patients With Newly Diagnosed Glioblastoma Multiforme

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00902577
First received: May 14, 2009
Last updated: November 21, 2014
Last verified: June 2014

May 14, 2009
November 21, 2014
August 2009
January 2018   (final data collection date for primary outcome measure)
Association of baseline FMISO PET uptake (HV and T/Bmax) and MRI parameters (Ktrans and CBV) with OS as assessed using Cox-regression model [ Time Frame: Up to 5 years after completion of study ] [ Designated as safety issue: No ]
The number of pixels in the tumor volume with a T/B ratio > 1.2, indicating hypoxia, is multiplied by the known volume/voxel for the scanner to yield milliliter units to measure the HV. T/Bmax is the pixel in the tumor region with the maximum T/B (tumor:blood) ratio. HV depicts the volume of tumor that has crossed the threshold for hypoxia and T/Bmax depicts the magnitude of the hypoxia. Uni-variate analysis will be carried out for each parameter individually. Any parameter that has achieved statistical significance (P =< 0.05) will be included in the multi-variate Cox model.
Relationship between overall survival (OS) and baseline FMISO PET uptake and MRI parameters [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00902577 on ClinicalTrials.gov Archive Site
  • Association of baseline FMISO PET uptake (HV and T/Bmax) and MRI parameters (Ktrans and CBV) with TTP and PFS-6 as assessed using multi-variate Cox model and multi-variate Logistic regression model [ Time Frame: Up to 5 years after completion of study ] [ Designated as safety issue: No ]

    Cox-regression model will be used to study the relationship between TTP and baseline FMISO PET uptake and MRI parameters. Logistic regression model will be used to study the relationship between PFS-6 and baseline FMISO PET uptake and MRI parameters. Uni-variate analysis will be carried out for each parameter individually. Any parameter that has achieved statistical significance (P=< 0.05) will be included.

    Disease progression defined by Macdonald criteria: >= 25% increase of enhancing tumor area; Neurological status worsened; Stable or increased dose of steroids

  • Reproducibility of the baseline FMISO PET uptake parameters as assessed by baseline "test" and "retest" PET scans [ Time Frame: Baseline and retest within 1 to 7 days after (but prior to the start of therapy) ] [ Designated as safety issue: No ]

    The reproducibility of the baseline FMISO PET will be quantified through intra-class correlation coefficient (ICC) which is defined as the ratio of σb^2 and (σb^2+ σc^2) where σb^2 is the variance of measurements between participants and σc^2 is the variance of measurements within participants.

    For a subset of 15 participants who enroll in the test-retest substudy only. Patients must be scanned using the same ACRIN-approved PET scanner used for trial qualification, using the same protocol-specific parameters consistently at each time point.

  • Correlation between T/Cmax and T/Bmax [ Time Frame: At baseline, week 4, and week 10 ] [ Designated as safety issue: No ]
    Pearson correlation coefficient and Spearman's rank correlation coefficient will be used to quantify the correlation between T/Cmax and T/Bmax.
  • Correlation between other MRI parameters (T1Gd, VCI, small vessel CBV, ADC, NAA-Cho ratio, changes in BOLD signal, and T2 lesion volume) and OS, TTP, and PFS-6 [ Time Frame: Up to 5 years after completion of study ] [ Designated as safety issue: No ]

    Other MRI parameters include: initial size of the lesion measured on T1 post Gd images [T1Gd], vessel caliber index [VCI], small vessel CBV, apparent diffusion coefficient [ADC], values measured from MR spectroscopy such as NAA-Cho ratio, changes in BOLD signal with transient exposure to hyperoxia, and T2 lesion volume.

    Cox-regression model will be used to study the relationship between OS and other MRI parameters. Logistic regression model will be used to study the relationship between PFS-6 and other MRI parameters. Uni-variate analysis will be carried out for each parameter individually.

  • Relationship between time to progression (TTP) and baseline FMISO PET uptake and MRI parameters [ Designated as safety issue: No ]
  • Relationship between of 6-month progression free survival (PFS-6) with FMISO PET uptake and MRI parameters [ Designated as safety issue: No ]
  • Relationship between OS, TTP, and PFS-6 with changes from baseline to week 4 in FMISO PET uptake and MRI parameters [ Designated as safety issue: No ]
  • Relationship between OS, TTP, and PFS-6 with changes from baseline to week 10 in FMISO PET uptake and MRI parameters [ Designated as safety issue: No ]
  • Reproducibility of the baseline FMISO PET uptake parameters by implemented baseline test and retest"PET scans performed within 1 to 7 days of each other [ Designated as safety issue: No ]
  • Correlation between T/Cmax (tumor:cerebellum) and T/Bmax (tumor:blood) at baseline, week 4, and week 10 [ Designated as safety issue: No ]
  • Relationship between other MRI parameters and OS, and PFS [ Designated as safety issue: No ]
Not Provided
Not Provided
 
MRI and PET Scan Using 18F-Fluoromisonidazole In Assessing Tumor Hypoxia in Patients With Newly Diagnosed Glioblastoma Multiforme
Multicenter, Phase II Assessment of Tumor Hypoxia in Glioblastoma Using 18F-Fluoromisonidazole (FMISO) With PET and MRI

This phase II trial is studying how well positron emission tomography (PET) scan using 18F-fluoromisonidazole works when given together with magnetic resonance imaging (MRI) ) in assessing tumor hypoxia in patients with newly diagnosed glioblastoma multiforme (GBM). Diagnostic procedures, such as MRI and PET scan using 18F-fluoromisonidazole (FMISO), may help predict the response of the tumor to the treatment and allow doctors to plan better treatment.

PRIMARY OBJECTIVES:

I. To determine the association of baseline FMISO PET uptake (hypoxic volume [HV]), highest tumor:blood ratio [T/Bmax]) and MRI parameters (Ktrans, CBV) with overall survival (OS) in participants with newly diagnosed GBM.

SECONDARY OBJECTIVES:

I. To determine the association of baseline FMISO PET uptake (HV, T/Bmax) and MRI parameters (Ktrans, CBV) with time to progression (TTP) and 6-month progression free survival (PFS-6) in participants with newly diagnosed GBM.

II. To assess the reproducibility of the baseline FMISO PET uptake parameters by implementing baseline "test" and "retest" PET scans (performed within 1 to 7 days of each other).

III. To assess the correlation between highest tissue:cerebellum ratio [T/Cmax] and T/Bmax at baseline.

IV. To assess the correlation between other MRI parameters (T1Gd, VCI, CBV-S, ADC, NAA-Cho, BOLD, T2) and OS, TTP, and PFS-6.

OUTLINE: This is a multicenter study.

Two weeks before initiation of chemoradiotherapy with temozolomide, patients undergo MRI and PET scan using FMISO. A subset of 15 patients undergo FMISO PET scans approximately 1 week before chemoradiotherapy. Blood samples are collected at baseline and periodically during study to compare image measures of tissue uptake of FMISO to blood concentrations. Tumor samples are collected from diagnostic biopsy or surgery for analysis of tumor hypoxic markers and methylguanine methyl transferase by immunohistochemical and PCR assays.

After completion of study therapy, patients are followed up every 3 months for up to 5 years.

Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
  • Adult Giant Cell Glioblastoma
  • Adult Glioblastoma
  • Adult Gliosarcoma
  • Drug: 18F-Fluoromisonidazole
    Undergo FMISO PET scans
    Other Names:
    • 18F-MISO
    • 18F-Misonidazole
    • FMISO
  • Procedure: Positron Emission Tomography
    Undergo FMISO PET scan
    Other Names:
    • Medical Imaging, Positron Emission Tomography
    • PET
    • PET Scan
    • Positron Emission Tomography
    • Positron Emission Tomography Scan
  • Procedure: Magnetic Resonance Imaging
    Undergo MRI
    Other Names:
    • Magnetic Resonance Imaging
    • Magnetic Resonance Imaging Scan
    • MRI
    • MRI Scan
    • NMRI
Experimental: Diagnostic (MRI and PET using FMISO)
Two weeks before initiation of chemoradiotherapy with temozolomide, patients undergo MRI and PET scan using FMISO. A subset of 15 patients undergo FMISO PET scans approximately 1 week before chemoradiotherapy.
Interventions:
  • Drug: 18F-Fluoromisonidazole
  • Procedure: Positron Emission Tomography
  • Procedure: Magnetic Resonance Imaging
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
50
Not Provided
January 2018   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Must be able to provide a written informed consent
  • Newly diagnosed GBM, World Health Organization (WHO) grade IV based on pathology confirmation
  • Residual tumor after surgery (amount of residual tumor will not impact patient eligibility and visible residual disease can include T2/FLAIR hyperintensity)

    • NOTE: If patient had a biopsy only, postoperative MRI is not needed to assess residual tumor prior to enrollment
  • Scheduled to receive standard fractionated radiation therapy
  • Scheduled to receive TMZ in addition to radiation therapy
  • Karnofsky Performance Score > 60

Exclusion Criteria:

  • Pregnant or breastfeeding (if a female is of child-bearing potential, and unsure of pregnancy status, a standard urine pregnancy test should be done)
  • Scheduled to receive chemotherapy, immunotherapy, or investigational agents in trials unwilling to share data with ACRIN (i.e., additional therapy added to radiation and TMZ is allowed if ACRIN is able to obtain treatment information)
  • Not suitable to undergo MRI or use the contrast agent Gd because of:
  • 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 GFR < 30 mL/min/1.73 m^2 based on a serum creatinine level obtained within 28 days prior to registration
  • Presence of any other co-existing condition which, in the judgment of the investigator, might increase the risk to the subject
  • Presence of serious systemic illness, including: uncontrolled intercurrent infection, uncontrolled malignancy, significant renal disease, or psychiatric/social situations which might impact the survival endpoint of the study or limit compliance with study requirements
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to FMISO; an allergic reaction to nitroimidazoles is highly unlikely
  • Not suitable to undergo PET or MRI, including weight greater than 350 lbs (the weight limit for the MRI and PET table)
  • Prior treatment with implanted radiotherapy or chemotherapy sources such as wafers of polifeprosan 20 with carmustine
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00902577
NCI-2011-01912, NCI-2011-01912, CDR0000640413, ACRIN 6684, ACRIN-6684, U01CA080098
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Elizabeth Gerstner American College of Radiology Imaging Network
National Cancer Institute (NCI)
June 2014

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