18F-Fluciclovine PET-MRI in High-grade Glioma

Official title

Evaluation of 18F-Fluciclovine PET-MRI to Differentiate Tumor Progression From Post-treatment Changes in Pediatric High-grade Glioma (HGG)

Overview

The purpose of this study is to see if 18F-fluciclovine (Axumin®) PET imaging is useful and safe in the management of children with High Grade Gliomas. Investigators seek to determine if this imaging will help doctors tell the difference between tumor growth (progression) and other tumor changes that can occur after treatment.

Detailed description

Following radiation and immunotherapy, many pediatric participants with high-grade gliomas (HGG), including diffuse midline glioma (DMG), demonstrate radiographic findings suspicious of disease progression. Differentiating post-treatment changes from true tumor progression is paramount to clinical decision-making, as true tumor progression may warrant a change in treatment, while post-treatment changes are typically not an indication to change treatment. Unfortunately, conventional MRI cannot reliably distinguish between true progression and post-treatment changes. Therefore, finding a physiological correlate to delineate true progression from pseudo-progression is critical.

The overall objective of this current application is to evaluate 18F-fluciclovine PET imaging as a diagnostic biomarker for tumor progression compared to post-treatment changes in pediatric HGG. The long-term goal of this research is to accurately differentiate tumor progression from post-treatment changes in pediatric HGG using 18F-fluciclovine PET imaging.

Interventions

• Drug 18F-Fluciclovine PET-MRI
  18F-Fluciclovine will be injected via IV prior to Positron emission tomography (PET)-Magnetic resonance imaging (MRI)

Primary outcome measures

• Image analysis [Time frame: 6 months]
• Histopathology analysis [Time frame: 4 weeks]

Secondary outcome measures (1)

• Safety of 18F-Fluciclovine [Time frame: 6 months]

Eligibility criteria

Inclusion criteria

• 1\. Histopathology-proven HGG (WHO grade III-IV) or DMG (WHO grade IV) or, in the case of DMG of the pons, imaging that is characteristic of Diffuse intrinsic pontine gliomas (DIPG) (diffusely infiltrating \>=2/3 of the pons).
• 2\. Measurable disease, measuring at least 1x1 cm.
• 3\. Life expectancy of greater than 8 weeks.
• 4\. Age \> 1 years but \< 21 years of age at enrollment.

For those without planned surgery:

• 1\. Participants with clinical and/or radiographic suspicion of True progression (TP) or Pseudoprogression (PsP) during radiation but yet to have the initial post-radiation MRI scan.

or

• 2\. Participants with suspicion for TP or PsP on first post-radiation MRI

For those with planned surgery:

• 1\. Clinical or radiographic suspicion of tumor progression with plan to undergo surgery or biopsy.

Exclusion criteria

• 1\. Inability to tolerate imaging procedures in the opinion of an investigator or treating physician.
• 2\. Pregnant or breastfeeding participants.
• 3\. Participant who would require sedation or anesthesia for imaging beyond standard of care (SOC).
• 4\. Participants who weigh less than 8 kg.
• 5\. Participants who cannot avoid contact with a pregnant woman or infant for at least 12 hours following injection.
• 6\. Participants with a history of abnormal kidney function or creatinine \>= CTCAE v5.0 grade 2 at time of study registration.

7\. Participants with primary tumors of the spinal cord.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Diagnostic

Study locations

United States · 1 center

• Children's Hospital of Philadelphia — Philadelphia

Publications

• Calmon R, Puget S, Varlet P, Dangouloff-Ros V, Blauwblomme T, Beccaria K, Grevent D, Sainte-Rose C, Castel D, Debily MA, Dufour C, Bolle S, Dhermain F, Saitovitch A, Zilbovicius M, Brunelle F, Grill J, Boddaert N. Cerebral blood flow changes after radiation therapy identifies pseudoprogression in diffuse intrinsic pontine gliomas. Neuro Oncol. 2018 Jun 18;20(7):994-1002. doi: 10.1093/neuonc/nox227 PMID 29244086
• Carceller F, Fowkes LA, Khabra K, Moreno L, Saran F, Burford A, Mackay A, Jones DT, Hovestadt V, Marshall LV, Vaidya S, Mandeville H, Jerome N, Bridges LR, Laxton R, Al-Sarraj S, Pfister SM, Leach MO, Pearson AD, Jones C, Koh DM, Zacharoulis S. Pseudoprogression in children, adolescents and young adults with non-brainstem high grade glioma and diffuse intrinsic pontine glioma. J Neurooncol. 2016 A PMID 27180091
• Vajapeyam S, Brown D, Billups C, Patay Z, Vezina G, Shiroishi MS, Law M, Baxter P, Onar-Thomas A, Fangusaro JR, Dunkel IJ, Poussaint TY. Advanced ADC Histogram, Perfusion, and Permeability Metrics Show an Association with Survival and Pseudoprogression in Newly Diagnosed Diffuse Intrinsic Pontine Glioma: A Report from the Pediatric Brain Tumor Consortium. AJNR Am J Neuroradiol. 2020 Apr;41(4):718- PMID 32241771
• Bhutia YD, Babu E, Ramachandran S, Ganapathy V. Amino Acid transporters in cancer and their relevance to "glutamine addiction": novel targets for the design of a new class of anticancer drugs. Cancer Res. 2015 May 1;75(9):1782-8. doi: 10.1158/0008-5472.CAN-14-3745. Epub 2015 Apr 8. PMID 25855379
• Galldiks N, Law I, Pope WB, Arbizu J, Langen KJ. The use of amino acid PET and conventional MRI for monitoring of brain tumor therapy. Neuroimage Clin. 2016 Dec 18;13:386-394. doi: 10.1016/j.nicl.2016.12.020. eCollection 2017. PMID 28116231
• Oka S, Hattori R, Kurosaki F, Toyama M, Williams LA, Yu W, Votaw JR, Yoshida Y, Goodman MM, Ito O. A preliminary study of anti-1-amino-3-18F-fluorocyclobutyl-1-carboxylic acid for the detection of prostate cancer. J Nucl Med. 2007 Jan;48(1):46-55. PMID 17204698
• Oka S, Okudaira H, Ono M, Schuster DM, Goodman MM, Kawai K, Shirakami Y. Differences in transport mechanisms of trans-1-amino-3-[18F]fluorocyclobutanecarboxylic acid in inflammation, prostate cancer, and glioma cells: comparison with L-[methyl-11C]methionine and 2-deoxy-2-[18F]fluoro-D-glucose. Mol Imaging Biol. 2014 Jun;16(3):322-9. doi: 10.1007/s11307-013-0693-0. PMID 24136390
• Zinnhardt B, Pigeon H, Theze B, Viel T, Wachsmuth L, Fricke IB, Schelhaas S, Honold L, Schwegmann K, Wagner S, Faust A, Faber C, Kuhlmann MT, Hermann S, Schafers M, Winkeler A, Jacobs AH. Combined PET Imaging of the Inflammatory Tumor Microenvironment Identifies Margins of Unique Radiotracer Uptake. Cancer Res. 2017 Apr 15;77(8):1831-1841. doi: 10.1158/0008-5472.CAN-16-2628. Epub 2017 Jan 30. PMID 28137769

Identifiers

NCT: NCT05553041 · 21-019514

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗