Clinical Trial · NCT00813566

Multi-Tracer PET Assessment of Primary Brain Tumors

Overview

The standard treatment approach for patients with high-grade primary brain tumors includes maximum feasible surgical resection, followed by 6 weeks of concurrent cranial irradiation and daily low-dose temozolomide chemotherapy, followed by 12 cycles of high-dose temozolomide administered for 5 consecutive days every 4 weeks \[Stupp 2005\]. Contrast-enhanced MRI is the current standard for evaluating the success of therapy and monitoring for tumor recurrence. MRI is typically obtained prior to initial surgery, within 24 hours after surgery, at the conclusions of cranial irradiation, and then every 8 weeks during temozolomide chemotherapy until evidence of recurrence. Despite this careful clinical and radiographic surveillance, and despite decades of research into the histologic and molecular classification of primary brain tumors, our ability to predict tumor behavior remains very limited. Some gliomas will result in overall survival times of only months, whereas other histologically-identical gliomas may yield survivals of years to decades \[Carson 2007, Curran 1993, Lamborn 2004\]. Current assessment of tumor response to therapy is also poor. Patients with complete radiographic response after cranial irradiation often progress rapidly post-irradiation. In contrast, some patients with enhancing masses at the end of chemoradiotherapy may respond dramatically to further chemotherapy alone, or the masses may even disappear in the absence of further therapy (so called "tumor pseudoprogression") \[Chamberlain 2007\]. This confounding situation demonstrates a need for better assessment of tumor response.

Sponsor

University of Utah

Phase

Phase 1

Contacts

Howard Colman, MD,PhD (STUDY_CHAIR)

Randy Jensen, MD,PhD (STUDY_CHAIR)

John M Hoffman, MD (PRINCIPAL_INVESTIGATOR)

Daniel Kadrmas, PhD (STUDY_CHAIR)

ClinicalTrials.gov

NCT00813566

Drug / Compound

FDG

Isotope(s):

Target(s):

Glucose Transport

Ligand Class: Small Molecules

FLT

Isotope(s):

Target(s):

cytosolic thymidine kinase 1

Ligand Class: Small Molecules

Acetate

Isotope(s):

Target(s):

Lipid/fatty acid synthesis

Ligand Class: Small Molecules

Eligibility

Inclusion

Group 2: Newly diagnosed primary malignant brain tumors (WHO Grade II - IV glial-based tumors) who have not had a complete surgical resection and by contrast MRI or CT have residual tumor greater than 1.0 cm in diameter and will be receiving radiotherapy and/or chemotherapy.
Three different adult patient groups will be eligible for inclusion in this study:
Karnofsky performance status ≥ 60%.
Group 1: Adult patients with compelling evidence of primary brain tumor based on clinical and MRI or CT imaging characteristics that have not yet received surgery, histological diagnosis, or any tumor-directed therapy. Such evidence will include: MRI or CT scan-documented mass lesion within the brain, accompanied by anatomically appropriate neurological signs and symptoms, in the absence of a probable competing diagnosis such as brain abscess or primary intracranial hematoma.
Determination of pregnancy status: Female patients that are not postmenopausal or surgically sterile will undergo a serum pregnancy test prior to each set of multi-tracer PET scans. A negative test will be necessary for such patients to undergo research PET imaging.
Pre-treatment laboratory tests for patients receiving \[18F\]FLT must be performed within 21 days prior to study entry. These must be less than 2.5 times below or above the upper or lower limit range for the respective laboratory test for entry into the study. In those instances where a baseline laboratory value is outside of this range, then such a patient will be ineligible for enrollment. For the follow-up scanning sessions after therapy has been instituted, laboratory testing will also be required due to the use of FLT. The patients have brain tumors and will receive various forms of therapy; therefore many routine laboratory tests may not be within the typical normal range. As such, a factor of 4.0 times above or below the upper or lower value for the normal range for any laboratory test will be used to determine the acceptable range for the 2nd and possible 3rd imaging timepoints. The baseline laboratory testing will include liver enzymes (ALT, aspartate aminotransferase (AST), alkaline phosphatase (ALK), LDH), bilirubin (total), serum electrolytes, complete blood count (CBC) with platelets and absolute neutrophil counts, prothrombin time, partial thromboplastin time, blood urea nitrogen (BUN), creatinine. Previous urinalysis abnormalities will not preclude the patient from being studied. For those patients receiving coumadin or another anticoagulant the upper limit for prothrombin time or partial thromboplastin time must not exceed 6 times the upper limit of the normal range.
Group 3: Patients with probable or possible recurrent primary brain tumor as determined by standard clinical criteria or MRI or CT imaging. The abnormality must be greater than or equal to 1.0 cm in diameter by contrast MRI or CT or show changes on non-enhancing MRI sequences (T2 or FLAIR).

Exclusion

HIV positive patients due to the previous toxicity noted with FLT in this patient group.
Patients with known allergic or hypersensitivity reactions to previously administered radiopharmaceuticals. Patients with significant drug or other allergies or autoimmune diseases may be enrolled at the Investigator's discretion.
Adult patients who require monitored anesthesia for PET scanning.
Patients who are pregnant or lactating or who suspect they might be pregnant. Serum pregnancy tests will be obtained prior to each set of multi-tracer PET scans in female patients that are not postmenopausal or surgically sterile.
Patients who have undergone surgery or receive any previous tumor-directed therapy for their brain tumor.
Patients with clinically significant signs of uncal herniation, such as acute pupillary enlargement, rapidly developing motor changes (over hours), or rapidly decreasing level of consciousness, are not eligible.