Clinical trial NCT00902577: MRI and PET/FMISO In Assessing Tumor Hypoxia in Patients With Newly Diagnosed Glioblastoma Multiforme
Official title: Multicenter, Phase II Assessment of Tumor Hypoxia in Glioblastoma Using 18F-Fluoromisonidazole (FMISO) With PET and MRI
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Adult Giant Cell Glioblastoma
Adult Glioblastoma
Adult Gliosarcoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2009-05-15
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: 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.

Detailed description: 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 (for example Gadolinium-enhanced T1-weighted (T1Gd), vessel caliber index (VCI), , CBV-S, apparent diffusion coefficient (ADC) , N-acetylaspartate (NAA) to choline (Cho) ratio, blood oxygenation level-dependent (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 Polymerase chain reaction (PCR) assays.

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

Eligibility criteria: Inclusion Criteria:

* Must be able to provide a written informed consent
* Newly diagnosed glioblastoma multiforme (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 Temozolomide (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 Glomerular Filtration Rate (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

Primary outcomes:
measure: Association of Baseline FMISO PET and MRI Features With OS as Assessed Using Cox-regression Model
timeFrame: "assessed from baseline up to 5 years, survival status at 1-year reported
Secondary outcomes:
measure: Association of Baseline FMISO PET and MRI Features With Time-to-Progression (TTP)
timeFrame: assessed from baseline up to 5 years, progression status at months 6 and 9 reported
measure: Reproducibility of the Baseline FMISO PET Uptake Parameters as Assessed by Baseline "Test" and "Retest" PET Scans
timeFrame: Baseline and retest within 1 to 7 days after (but prior to the start of therapy)
measure: Correlation Between T/Cmax and T/Bmax
timeFrame: At baseline
measure: Correlation Between MRS Markers and MR Imaging Markers of Vascularity as Well as Between MRS Markers and PET Markers of Tumor Hypoxia
timeFrame: baseline
Other outcomes:
measure: Overall and Progression Free Survival
timeFrame: Baseline, every 3 months through study completion (up to 5 years for progression and survivorship)
measure: SUVpeak and T/Bmax as Measures of Tumor Hypoxia
timeFrame: baseline
measure: Hypoxic Volume as a Measure of Tumor Hypoxia
timeFrame: baseline
measure: DWI Apparent Diffusion Coefficient (ADC)
timeFrame: baseline
measure: Normalized Relative Cerebral Blood Volume (nRCBV) and Normalized Cerebral Blood Flow (nCBF)
timeFrame: baseline
measure: Summary of Mean and Median Ktrans Across Participants.
timeFrame: baseline
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Cancer Center
state: Alabama
city: Los Angeles
country: United States
facility: USC / Norris Comprehensive Cancer Center
state: California
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Baltimore
country: United States
facility: Johns Hopkins University/Sidney Kimmel Cancer Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Mount Sinai Hospital
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
state: Ohio
city: Philadelphia
country: United States
facility: American College of Radiology Imaging Network
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania/Abramson Cancer Center
state: Pennsylvania
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
Study officials:
affiliation: American College of Radiology Imaging Network
name: Elizabeth Gerstner
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ratai EM, Zhang Z, Fink J, Muzi M, Hanna L, Greco E, Richards T, Kim D, Andronesi OC, Mintz A, Kostakoglu L, Prah M, Ellingson B, Schmainda K, Sorensen G, Barboriak D, Mankoff D, Gerstner ER; ACRIN 6684 trial group. ACRIN 6684: Multicenter, phase II assessment of tumor hypoxia in newly diagnosed glioblastoma using magnetic resonance spectroscopy. PLoS One. 2018 Jun 14;13(6):e0198548. doi: 10.1371/journal.pone.0198548. eCollection 2018.
citation: Gerstner ER, Zhang Z, Fink JR, Muzi M, Hanna L, Greco E, Prah M, Schmainda KM, Mintz A, Kostakoglu L, Eikman EA, Ellingson BM, Ratai EM, Sorensen AG, Barboriak DP, Mankoff DA; ACRIN 6684 Trial Group. ACRIN 6684: Assessment of Tumor Hypoxia in Newly Diagnosed Glioblastoma Using 18F-FMISO PET and MRI. Clin Cancer Res. 2016 Oct 15;22(20):5079-5086. doi: 10.1158/1078-0432.CCR-15-2529. Epub 2016 May 16.