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

Glioblastoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01880008
• Other study ID #: 08-0073
• Status: Completed
• Phase: N/A
• First received: July 30, 2010
• Last updated: June 13, 2013
• Start date: April 2008
• Est. completion date: August 2012

Study information

• Verified date: June 2013
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5
• Est. completion date: August 2012
• Est. primary completion date: February 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Observational Model: Case-Only, Time Perspective: Prospective

Related Conditions & MeSH terms

• Glioblastoma

Locations

Country	Name	City	State
United States	Washington University School of Medicine/Barnes-Jewish Hospital	St. Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Washington University School of Medicine	Barnes-Jewish Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Survival	Number of months from date of diagnosis to date of death.	2 years	No
Secondary	Ki-67	Ki-67 proliferation index on tumor specimens obtained at biopsy or from surgical resection specimen	At diagnosis	No
Secondary	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	No
Secondary	O(6)-methylguanine DNA-methyltransferase (MGMT) activity	MGMT activity from tumor specimens	prior to treatment	No
Secondary	Time to progression	Months after completing radiation treatment to first instance of radiographic progression	2 years	No