[F-18] Fluorothymidine (FLT) Imaging on Patients With Primary Brain Tumors

NCT00707343 | Completed Phase 1 Results DMC

• 1 other identifier: HCI20112
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Despite significant advances in the understanding of brain tumor biology and genetics as well as improvements in surgical techniques, radiotherapy administration, and chemotherapy methods, many primary brain tumors remain incurable. Most primary brain tumors are highly infiltrative neoplasms, and are therefore unlikely to be cured by local treatments such as surgery, focal radiotherapy, radiosurgery or brachytherapy. A particularly problematic aspect of the management of patients with brain tumors is the eventual development of enhancing lesions on MRI after radiation therapy. The treating physician is then left with the dilemma of what this enhancing lesion may represent (radiation necrosis versus recurrent tumor). The differential diagnosis is between recurrent tumor or radiation necrosis however the amount of each contributing to the enhancing mass on MRI is difficult if not impossible to assess. This particular problem is very common and most patients develop some degree of radiation necrosis after therapy with radiation. Differentiation of necrosis from recurrence is particularly challenging. MRI is typically unable to make this important distinction as there is simply an enhancing mass, the etiology of which could be either necrosis or recurrence. Other imaging methods such as FDG-PET have been used but this technique is also complicated in that the normal brain has FDG uptake and it is often difficult to differentiate recurrence from necrosis. \[F-18\]FLT may prove to be the most reliable method in making this important differentiation (necrosis versus recurrence) as normal brain and necrotic brain do not have proliferative activity and thus no \[F-18\]FLT uptake whereas tumor will have proliferative activity and thus \[F-18\]FLT uptake.

Conditions

Cancer; Brain Tumors

Outcome Measures

Primary Outcomes (1)

• Area Under the Receiver Operating Curve (ROC AUC) Values for PET Imaging Techniques

  The ROC AUC represents the probability that tumor recurrence will be differentiated from radiation necrosis. Positron Emission Tomography (PET) imaging methods using radiopharmaceutical agents F-18 fluorodeoxyglucose (FDG) and F-18 fluorothymidine (FLT) were used for analysis. For F-18 FDG, the maximum standardized uptake value (SUVmax) with correction for body weight was measured at suspicious area of lesion enhancement. The ratio of F-18 FDG SUVmax of the suspicious lesion to that of the SUVmean of a 1 cm diameter region of normal contralateral white matter was also measured (F-18 FDG ratio lesion: contralateral white matter). For F-18 FLT, the maximum standardized uptake value (SUVmax) was measured at suspicious area of lesion enhancement. Patlak graphical analysis was applied using the metabolite-corrected plasma input function to obtain voxel-wise estimates of the FLT metabolic influx parameter (F-18 FLT Kimax).

  30 minutes for FDG imaging, 70 minutes for FLT imaging acquisition; 2-33 months for lesion outcome confirmation

Study Arms (1)

All patients

EXPERIMENTAL

All participants enrolled.

Radiation: FLT-PET Imaging

Interventions

FLT-PET Imaging RADIATION

radiopharmaceutical 3'-deoxy-3'-\[F-18\]fluorothymidine, \[F-18\]FLT, a radiopharmaceutical that directly assess tumor proliferation using Positron Emission Tomography(PET) in differentiating tumor recurrence from radiation necrosis in a group of patients with glial neoplasms.

All patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients (n = 20) with primary brain tumors will be studied.
• All patients will have had previous radiation and may or may not have had chemotherapy for treatment of the primary brain tumor.
• After entry into the study, the initial 12 patients are expected to be followed for at least 1 month after the infusion of \[F-18\]FLT.
• The patient, if female, must be postmenopausal for a minimum of one year or surgically sterile, or on one of the following methods of birth control for a minimum of one month prior to entry into this study: IUD, oral contraceptives, Depo-Provera or Norplant. These criteria can be waived at the discretion of the investigator if the patient's intracranial tumor is considered life threatening and the one month wait required is not in the best interest of the patient. Negative pregnancy test is accepted.
• Pre-treatment laboratory tests for patients receiving \[F-18\]FLT must be performed within 14 days prior to study entry. These must no greater or less than 4X the normal upper or lower limits. These will include liver enzymes (SGOT, SGPT, ALK Phos, GGT, LDH), bilirubin (direct and total), amylase, serum electrolytes, CBC with platelets and absolute neutrophil counts, prothrombin time, partial thromboplastin time, BUN, creatinine, and urinalysis.
• Pre-treatment radiological scans/studies (Gd- enhanced MRI and FDG-PET) for patients receiving \[F-18\]FLT must be performed within 10 days of study entry.

You may not qualify if:

• 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.
• 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.
• Patients who are pregnant or lactating or who suspect they might be pregnant.
• Adult patients who require monitored anesthesia for PET scanning.
• HIV positive patients due to the previous toxicity noted with FLT in this patient group.

Sponsors & Collaborators

• University of Utah: lead

Study Sites (1)

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Neoplasms; Brain Neoplasms

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Results Point of Contact

• Title: Mark Wade, Ph.D. - Compliance Officer
• Organization: Huntsman Cancer Institute

mark.wade@hci.utah.edu

801-213-5746

Study Officials

• John M Hoffman, MD

  Huntsman Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2008
• First Posted: June 30, 2008
• Study Start: October 31, 2007
• Primary Completion: November 30, 2010
• Study Completion: November 30, 2010
• Last Updated: October 15, 2021
• Results First Posted: February 3, 2016

Record last verified: 2021-09

Locations

US (1)