Multi-Tracer PET Assessment of Primary Brain Tumors
|First Received Date ICMJE||December 16, 2008|
|Last Updated Date||June 21, 2016|
|Start Date ICMJE||December 2008|
|Estimated Primary Completion Date||July 2018 (final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
|Original Primary Outcome Measures ICMJE
|Change History||Complete list of historical versions of study NCT00813566 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Multi-Tracer PET Assessment of Primary Brain Tumors|
|Official Title ICMJE||Multi-Tracer PET Assessment of Primary Brain Tumors|
|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.|
Positron emission tomography (PET) is a molecular imaging modality that can probe various aspects of tumor function using a variety of radio-labeled imaging agents ("tracers"). Oncologic PET imaging has seen a dramatic rise in clinical utilization over the past decade for cancer detection, staging, and evaluating residual or recurrent disease following therapy. These clinical scans use the tracer [18F]fluoro-2-deoxy-D-glucose (FDG), which accumulates in cells in proportion to GLUT transporter and hexokinase activity. FDG thus provides a measure of tissue glucose metabolism. Concurrent with this clinical growth, a number of other PET tracers have received significant attention in research for a variety of imaging targets. Of special interest are the tracers 3'-deoxy-3'-[18F]fluorothymidine (FLT), 1-[11C]-acetate (ACE), and [15O]water (H2O). The uptake, retention/washout, and ultimate biodistribution of these tracers are each related to different functional or molecular processes. As such, each can be used to probe a different aspect of tumor function: FLT directly assesses tumor proliferation, ACE provides a measure of tumor growth related to fatty acid and membrane synthesis, and H2O quantifies tumor perfusion.
This study has two primary objectives: a translational objective in which a new PET imaging technology will be translated from experimental development (with simulations and in animals) to the first use in human subjects; and an exploratory objective in which the complementary value of multiple PET tracers will be investigated. Each of these objective is described below, where the study design has been carefully setup to fulfill both objectives in the same study population.
The translational objective of this study is to implement and evaluate a new imaging technology for rapid, single-scan multi-tracer PET imaging of these tracers. Current PET technology prohibits imaging of more than one tracer in a single scan since the imaging signals from each tracer cannot be distinguished by normal techniques; as such, separate scans with each tracer currently need to be acquired hours or days apart. Our group has developed techniques and algorithms for recovering individual-tracer images from rapidly-acquired multi-tracer PET data using dynamic imaging techniques. These methods have been tested through extensive simulations and verified experimentally in a canine model with spontaneously-occurring tumors. Refinement of the methods with more advanced algorithms is ongoing. The patient imaging studies of this protocol will be implemented in two phases. In Phase A, separate single-tracer imaging of each tracer will be performed. The data from these scans will be co-registered and combined to "emulate" multi-tracer scans, which will then be processed by the multi-tracer signal-separation algorithms. This will permit a direct comparison of imaging biomarkers from multi-tracer vs. single-tracer scans for each tracer. Such comparison techniques have been established by the investigators and have been accepted by peer review for testing multi-tracer signal-separation algorithms. Once statistically-significant evidence is obtained that multi-tracer scans can accurately provide the same imaging biomarkers as separate single-tracer scans, the imaging will transition to Phase B—in which actual multi-tracer scans will be performed.
The objectives of this exploratory study is to preliminarily evaluate the complementary value of FDG, FLT, ACE, and H2O PET in patients with primary glial neoplasms. Multi-tracer PET profiles with these four tracers will be obtained in 20 patients with primary glial neoplasms at up to three timepoints: (1) at "baseline" prior to surgery or immediately after surgery providing a complete surgical resection was not possible and confirmed by a post-operative contrast MRI scan where residual tumor greater than 1.0 cm in diameter was present and prior to any tumor-directed therapy; (2) at the conclusions of the initial (~6-8 weeks) chemoradiotherapy; and (3) at the time of MRI-documented recurrence within 2 years. In addition, patients with a known primary brain tumor who have previously undergone treatment and have recurred based on standard clinical and imaging criteria will be eligible for the study. A number of quantitative and pseudo-quantitative imaging biomarkers for each tracer will be computed at each imaging timepoint, and the change in each biomarker between timepoints will also be computed. These data will be compared with clinical endpoints (survival, time to progression), and with tumor biologic information (histology, WHO grade, vascularity, Ki-67, VEGF, EGFR, p53) in cases when tumor tissue becomes available from standard care. These data will provide pilot information into the potential value of concurrent multiple PET biomarkers for predicting tumor behavior prior to the start of therapy, for improved prognostication, for more efficient and effective tumor surveillance, and/or for more appropriate assignment of patients to conventional, aggressive, or investigational therapies early in their clinical courses.
The driving hypothesis for the overall line of research is that multiple PET imaging biomarkers obtained in conjunction can provide improved image-guided personalized care of patients with primary glial neoplasms. The term "personalized care" is used here to broadly include the prediction of tumor behavior prior to the start of therapy, tumor surveillance, prognostication, and individualized assignment of patients to conventional, aggressive, or investigational therapies early in their clinical courses. This pilot project will obtain initial data on the value of these PET biomarkers for such image-guided personalized care.
Specific hypotheses to be tested include:
a Sufficient statistical power is expected to be obtained under this protocol to validate the extensive simulations and experimental evaluations performed previously and concurrently with these patient imaging studies.
b Pilot data regarding these three hypotheses will be obtained in this work by studying the correlation of PET imaging biomarkers with clinical outcomes and tumor biologic information. Though high statistical power cannot be expected from the limited number of patients in this pilot study, underlying trends in the data will be identified, permitting the formulation of formal hypotheses to be tested in future rigorous trials.
|Study Type ICMJE||Observational|
|Study Design ICMJE||Observational Model: Case-Only
Time Perspective: Prospective
|Target Follow-Up Duration||Not Provided|
|Sampling Method||Non-Probability Sample|
|Study Population||Study patients: Adult patients (n = 20) with (Group 1) compelling MRI evidence of a new primary brain tumor who have not yet undergone surgery or any tumor-directed therapy, or (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 have residual tumor greater than 1.0 cm in diameter and will be receiving radiotherapy and/or chemotherapy, or (Group 3) patients with recurrent primary barin tumor as determined by standard clinical criteria and MRI imaging. Four to eight patients per year will be enrolled during the first 3 years, for a total of 20 patients. Enrollment will be weighted toward lower-grade tumors during year 1 in order to allow for longer followup times during the life of the project. Dr. Jensen or Dr. Colman will identify and recruit patients for participation and obtain informed consent.|
|Intervention ICMJE||Radiation: Multi-tracer PET exams of 18F-FDG, 18F-FLT, 11C-ACE, and 15O-H2O
|Study Group/Cohort (s)||Diagnostic
Intervention: Radiation: Multi-tracer PET exams of 18F-FDG, 18F-FLT, 11C-ACE, and 15O-H2O
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Estimated Enrollment ICMJE||20|
|Estimated Completion Date||July 2018|
|Estimated Primary Completion Date||July 2018 (final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
Three different adult patient groups will be eligible for inclusion in this study:
|Ages||18 Years and older (Adult, Senior)|
|Accepts Healthy Volunteers||No|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT00813566|
|Other Study ID Numbers ICMJE||HCI31335|
|Has Data Monitoring Committee||Yes|
|Plan to Share Data||Not Provided|
|IPD Description||Not Provided|
|Responsible Party||University of Utah|
|Study Sponsor ICMJE||University of Utah|
|Collaborators ICMJE||Not Provided|
|Information Provided By||University of Utah|
|Verification Date||June 2016|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP