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Multicenter, Phase II Assessment of Tumor Hypoxia in Glioblastoma Using 18F-Fluoromisonidazole (FMISO) With PET and MRI


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma

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Trial Information

Multicenter, Phase II Assessment of Tumor Hypoxia in Glioblastoma Using 18F-Fluoromisonidazole (FMISO) With PET and MRI


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.


Inclusion Criteria:



- Pathologically confirmed glioblastoma multiforme

- Newly diagnosed disease

- Grade IV according to WHO criteria

- Residual tumor required after surgery, including T2/FLAIR hyperintensity

- Amount of residual tumor will not impact patient eligibility

- Scheduled to receive standard fractionated radiation therapy and temozolomide

- May also receive an anti-VEGF or PARP-inhibiting therapy

- Karnofsky performance status 60-100%

- Not pregnant or nursing

- Negative pregnancy test

- Able to undergo MRI and use gadolinium-contrast agent, meeting the following
criteria:

- No claustrophobia

- No metallic objects or implanted medical devices in the 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)

- No sickle cell disease

- No renal failure

- No reduced renal function, as determined by glomerular filtration rate < 30
mL/min based on a serum creatinine level obtained within 28 days prior to study
entry

- No other concurrent condition that, in the judgment of the investigator, might
increase patient's risk

- No concurrent serious systemic illness, including any of the following:

- Uncontrolled intercurrent infection

- Uncontrolled malignancy

- Significant renal disease

- Psychiatric or social situations that might impact the survival endpoint of the
study or limit compliance with study requirements

- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to FMISO

- Able to undergo PET or MRI (i.e., weight ≤ 350 lbs)

- Able to tolerate 100% oxygen < 10 minutes (e.g., no history of chronic obstructive
pulmonary disease)

- No prior implanted radiotherapy or chemotherapy sources (i.e., wafers of polifeprosan
20 with carmustine)

- Not scheduled to receive chemotherapy, immunotherapy, or biologic agent other than
temozolomide, including any anti-tumor investigational agent

- Concurrent anti-VEGF agent allowed

Type of Study:

Interventional

Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

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

Outcome Description:

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.

Outcome Time Frame:

Up to 5 years after completion of study

Safety Issue:

No

Principal Investigator

Elizabeth Gerstner

Investigator Role:

Principal Investigator

Investigator Affiliation:

American College of Radiology Imaging Network

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2011-01912

NCT ID:

NCT00902577

Start Date:

August 2009

Completion Date:

Related Keywords:

  • Adult Giant Cell Glioblastoma
  • Adult Glioblastoma
  • Adult Gliosarcoma
  • Glioblastoma
  • Gliosarcoma
  • Anoxia

Name

Location

Abramson Cancer Center of the University of PennsylvaniaPhiladelphia, Pennsylvania  19104-4283
Dana-Farber Harvard Cancer CenterBoston, Massachusetts  02115
American College of Radiology Imaging NetworkPhiladelphia, Pennsylvania  19103
Johns Hopkins University CCOPBaltimore, Maryland  21287