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

Completed
Conditions
Glioblastoma
Registration Number
NCT01880008
Lead Sponsor
Washington University School of Medicine
Brief 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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
5
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.
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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.
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Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Change in FLT uptake, measured by SUV tumor/SUV normal contralateral white matterBefore and after chemotherapy/radiation therapy

Determines the change in FLT uptake as a result of chemotherapy/radiation therapy

Secondary Outcome Measures
NameTimeMethod
Survival2 years

Number of months from date of diagnosis to date of death.

Ki-67At diagnosis

Ki-67 proliferation index on tumor specimens obtained at biopsy or from surgical resection specimen

Radiographic progression defined by MacDonald criteria2 years

MacDonald criteria to be used to determine whether tumor progress or not during the course of this study

O(6)-methylguanine DNA-methyltransferase (MGMT) activityprior to treatment

MGMT activity from tumor specimens

Time to progression2 years

Months after completing radiation treatment to first instance of radiographic progression

Trial Locations

Locations (1)

Washington University School of Medicine/Barnes-Jewish Hospital

🇺🇸

St. Louis, Missouri, United States

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