Evaluation of FLT PET and MRI as Imaging Biomarkers of Early Treatment Response in Patients With Glioblastoma

An Exploratory Study of Quantitative [18F]FLT-PET and Advanced MRI as Early Indicators of Treatment Response and Molecular Markers for Cell Proliferation in Patients With Glioblastoma Following Subtotal Resection

Glioblastoma is the most common primary malignant neoplasm of the adult brain. Even after multimodal therapy, outcomes remain poor, with a median survival of one year. Although advanced imaging methods have been suggested as molecular markers of prognosis and therapeutic response, these methods have not been validated for clinical use. In this exploratory, imaging-based, trial, thirty patients with a pathological diagnosis of glioblastoma will be followed prospectively for two years. The study examines how PET and MR imaging signals change following administration of a standard radio-chemotherapy treatment regimen to determine whether these imaging modalities can provide early indicators of response to therapeutic intervention. The investigators hypothesize that decreases in uptake of an investigational 18F-FLT PET tracer following treatment with radiation and chemotherapy will be a reliable predictor of glioblastoma response. In a more exploratory fashion, the investigators also will identify changes in diffusion and hypoxia MR imaging that may also correlate well with treatment response.

Study Overview

• Status: Completed
• Conditions: Glioblastoma

Detailed Description

Patients with glioblastoma will be imaged with FLT PET/CT followed by MRI. The FLT uptake will be correlated with advanced MRI markers of tumor progression to determine the ability of using FLT PET and MRI for predicting response to treatment.

• Study Type: Observational
• Enrollment (Actual): 5

Contacts and Locations

Study Locations

• United States
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Washington University School of Medicine/Barnes-Jewish Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with WHO grade III or IV glioma

Description

Inclusion Criteria:

• Adult patients (> 18 yo) with a pathological diagnosis of malignant glioma (WHO grades III and IV, including all histological subtypes)
• Surgical intervention includes subtotal resection or biopsy with MRI evidence of residual disease after resection
• Patients with plan to undergo standard chemotherapy and radiation protocols including a combination of fractionated radiation and temozolomide
• Preoperative Karnofsky performance score (KPS) of > 60
• Willingness of patient and his/her partner to use contraceptive measures for duration of trial that will include PET studies.

Exclusion Criteria:

• Patient refuses adjunctive therapy
• Pregnancy
• Karnofsky scale < 60
• Inability to undergo MR imaging studies
• Estimated GFR ≤ 60 ml/min (using GFR = 0.85*[140 - age(y)]*[bodyweight(kg)]/[72*Cr(mg/dl)] for women and GFR = [140 - age(y)]*[bodyweight(kg)]/[72*Cr(mg/dl)] for men).
• Inability or unwillingness to follow instructions for both PET and MR imaging sessions.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Treatment; All patients included in this study were treated with temozolomide and radiotherapy after subtotal resection of a WHO grade III or IV glioma.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in FLT uptake, measured by SUV tumor/SUV normal contralateral white matter	Determines the change in FLT uptake as a result of chemotherapy/radiation therapy	Before and after chemotherapy/radiation therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival	Number of months from date of diagnosis to date of death.	2 years
Ki-67	Ki-67 proliferation index on tumor specimens obtained at biopsy or from surgical resection specimen	At diagnosis
Radiographic progression defined by MacDonald criteria	MacDonald criteria to be used to determine whether tumor progress or not during the course of this study	2 years
O(6)-methylguanine DNA-methyltransferase (MGMT) activity	MGMT activity from tumor specimens	prior to treatment
Time to progression	Months after completing radiation treatment to first instance of radiographic progression	2 years

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: Barnes-Jewish Hospital
• Investigators: Principal Investigator: Delphine L Chen, MD, Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (Actual): February 1, 2010
• Study Completion (Actual): August 1, 2012

Study Registration Dates

• First Submitted: July 30, 2010
• First Submitted That Met QC Criteria: June 13, 2013
• First Posted (Estimate): June 18, 2013

Study Record Updates

• Last Update Posted (Estimate): June 18, 2013
• Last Update Submitted That Met QC Criteria: June 13, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Keywords: magnetic resonance imaging; radiation therapy; positron emission tomography; diffusion magnetic resonance imaging; radionuclide imaging; disease management
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma
• Other Study ID Numbers: 08-0073