Multi-Tracer PET Assessment of Primary Brain Tumors

NCT00813566 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: HCI31335
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Brain Tumors; Cancer

Keywords

cancer; imaging; PET scanning

Outcome Measures

Primary Outcomes (4)

• Rapid, single-scan multi-tracer PET imaging can recover PET imaging biomarker information of each tracer that are not significantly different from those obtained from conventional, single-tracer scans of each tracer.

  June 2014

• Multi-tracer PET biomarkers, obtained in conjunction, are better able to predict tumor aggressiveness than individual-tracer biomarkers or conventional radiographic imaging.

  June 2014

• Multi-tracer PET biomarkers, obtained in conjunction, are better able to detect functional changes in tumor state that occur in response to therapy than individual-tracer biomarkers or conventional radiographic imaging.

  June 2014

• Characterization of multiple aspects of tumor function (glucose metabolism, proliferation, membrane growth, and perfusion) provides new insight into tumor status that can guide selection of the most appropriate therapy.

  June 2014

Study Arms (1)

All Participants

EXPERIMENTAL

All participants will receive multi-tracer PET scans at up to 3 time points: baseline, at the conclusion of standard of care chemoradiation, and at the time of documented recurrence within two years.

Drug: [18F]fluoro-2-deoxy-D-glucose (FDG); Drug: 3'-deoxy-3'-[18F]fluorothymidine (FLT); Drug: [15O]-H2O; Drug: [11C]Acetate

Interventions

[18F]fluoro-2-deoxy-D-glucose (FDG) DRUG

Brain scan with metabolic imaging tracer that aids in assessment, diagnosis, and staging of patients with cancer.

Also known as: FDG, [18F]FDG, FDG-PET/CT

All Participants

3'-deoxy-3'-[18F]fluorothymidine (FLT) DRUG

Brain scan with a radiolabeled imaging agent for investigating cellular proliferation of tumors

Also known as: [18F]FLT, FLT

All Participants

[15O]-H2O DRUG

Brain scan with imaging agent to determine tumor blood flow

Also known as: H2[15O], [15O]water

All Participants

[11C]Acetate DRUG

Brain scan with imaging agent to determine growth activity of tumor

Also known as: [11C]ACE, ACE

All Participants

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.
• 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).
• Karnofsky performance status ≥ 60%.
• Patients must document their willingness to be followed for at least 24 months after recruitment by signing informed consent documenting their agreement to have clinical endpoints and the results of histopathologic tissue analysis (when tissue becomes available from routine care) entered into a research database.
• All patients, or their legal guardians, must sign a written informed consent and HIPAA authorization in accordance with institutional guidelines.
• 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.

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. 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.
• Adult patients who require monitored anesthesia for PET scanning.
• HIV positive patients due to the previous toxicity noted with FLT in this patient group.
• Patients who have undergone surgery or receive any previous tumor-directed therapy for their brain tumor.

Sponsors & Collaborators

• University of Utah: lead

Study Sites (1)

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Brain Neoplasms; Neoplasms

Interventions

Fluorodeoxyglucose F18; alovudine; carbon-11 acetate

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Deoxyglucose; Deoxy Sugars; Carbohydrates

Study Officials

• John M Hoffman, MD

  Huntsman Cancer Institute

  PRINCIPAL INVESTIGATOR

• Daniel Kadrmas, PhD

  Huntsman Cancer Institute

  STUDY CHAIR

• Randy Jensen, MD,PhD

  Huntsman Cancer Institute

  STUDY CHAIR

• Howard Colman, MD,PhD

  Huntsman Cancer Institute

  STUDY CHAIR

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: December 16, 2008
• First Posted: December 23, 2008
• Study Start: November 12, 2010
• Primary Completion: February 3, 2015
• Study Completion: February 3, 2015
• Last Updated: April 27, 2022

Record last verified: 2022-04

Locations

US (1)