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

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:

- 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