[18F]Fluciclovine and [18F]FLT PET/CT Assessment of Primary High-Grade Brain Tumors
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|ClinicalTrials.gov Identifier: NCT03276676|
Recruitment Status : Recruiting
First Posted : September 8, 2017
Last Update Posted : December 4, 2019
|Condition or disease||Intervention/treatment||Phase|
|Brain Tumor||Drug: Multi-tracer PET exams of [18F]FLT and [18F]Fluciclovine||Phase 2|
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 et al., 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 (Curran et al., 1993, Carson et al., 2007). 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 et al., 2007). This confounding situation demonstrates a need for better assessment of tumor response.
Improvements in the ability to predict tumor behavior prior to the start of therapy would allow more efficient and effective tumor surveillance; better prognostication; and more appropriate assignment of patients to conventional, aggressive, or investigational therapies early in their clinical courses. This would provide huge economic and social benefits, and could afford decisive insights into brain tumor physiology and biology.
Similarly, the ability to identify, earlier and more accurately, whether individual patients were responding to therapy would allow prompt discontinuation of ineffectual treatments and institution of potentially more effective therapies.
Previous efforts using imaging for such tasks have generally been limited to a single modality (e.g. MRI) and/or single-tracer (e.g. FDG-PET). However, there is a significant and growing body of evidence that complementary imaging of multiple aspects of tumor physiology (i.e. using multiple PET tracers) can provide greatly enhanced information over imaging with a single modality or tracer alone. In solid tumors, complex interactions exist between blood flow, metabolic activity, and oxygen status which affect metastatic and proliferative activity. Heterogeneous tumors may contain both slow-growing and fast-growing regions that present different profiles of proliferation rates and amino acid uptake.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||[18F]Fluciclovine and [18F]FLT PET/CT Assessment of Primary High-Grade Brain Tumors|
|Actual Study Start Date :||March 6, 2018|
|Estimated Primary Completion Date :||November 2022|
|Estimated Study Completion Date :||November 2022|
Experimental: All Enrolled participants
Multi-tracer PET exams of [18F]FLT and [18F]Fluciclovine
Drug: Multi-tracer PET exams of [18F]FLT and [18F]Fluciclovine
Multi-tracer PET exams of [18F]FLT and [18F]Fluciclovine will be acquired in each patient at up to three time points: (1) prior to any tumor-directed therapy, either prior to surgery or immediately after surgery providing a complete surgical resection was not performed and confirmed by a post-operative contrast MRI scan where residual tumor > 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) patients with MRI-documented possible recurrence/progression versus treatment effect (pseudoprogression) within 6 months from the time of completion of chemoradiation.
- Increased Overall Survival [ Time Frame: 2 years ]a 25% reduction in SUVmax (Standardized uptake value) or SUVmean for each of the PET imaging tracers will be predictive of increased overall survival
- Association between overall survival and quantitative markers [ Time Frame: Within 6 months of chemoradiation ]Assess the association between overall survival and change in each of the following quantitative markers for [18F]Fluciclovine and [18F]FLT: K1-k4, Knet and Ktrans, from baseline to post therapy.
- Association between progression free survival and quantitative markers [ Time Frame: Within 6 months of chemoradiation ]Assess the association between progression free survival and change in each of the following quantitative markers for [18F]Fluciclovine and [18F]FLT: K1-k4, Knet and Ktrans, from baseline to post therapy.
- Ability of [18F]FLT and/or [18F]Fluciclovine alone or together to predict true progression from pseudoprogression [ Time Frame: Through study completion, an average of 6 months ]Assess the ability of [18F]FLT and/or [18F]Fluciclovine alone or together to predict true progression from pseudoprogression in patients with this clinical dilemma.
- More predictive of overall survival than an MRI [ Time Frame: 2 years ]A 25% reduction in SUVmax or SUVmean for each of the PET imaging tracers will be more predictive of overall survival than the current MRI based response criteria.
- More predictive of time to progression than an MRI [ Time Frame: 2 years ]A 25% reduction in SUVmax or SUVmean for each of the PET imaging tracers will be more predictive of time to progression than the current MRI based response criteria.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03276676
|Contact: Paige Nielsenemail@example.com|
|United States, Utah|
|Huntsman Cancer Institute||Recruiting|
|Salt Lake City, Utah, United States, 84112|
|Contact: Paige Nielsen 801-585-5942 firstname.lastname@example.org|
|Principal Investigator: John Hoffman, MD|
|Principal Investigator:||John Hoffman, MD||University of Utah|