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A phase IIa trial of molecular radiotherapy with 177-lutetium DOTATATE in children with primary refractory or relapsed high-risk neuroblastoma

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

The objective of this phase IIa, open-label, single-centre, single-arm, two-stage clinical trial was to evaluate the safety and activity of 177-lutetium DOTATATE (LuDO) molecular radiotherapy in neuroblastoma.

Methods

Children with relapsed or refractory metastatic high-risk neuroblastoma were treated with up to four courses of LuDO. The administered activity was 75 to 100 MBq kg−1 per course, spaced at 8- to 12-week intervals. Outcomes were assessed by the International Neuroblastoma Response Criteria (primary outcome), progression-free survival (PFS), and overall survival (OS).

Results

The trial recruited 21 patients; eight received the planned four courses. There was dose-limiting haematologic toxicity in one case, but no other significant haematologic or renal toxicities. None of 14 evaluable patients had an objective response at 1 month after completion of treatment (Wilson 90% CI 0.0, 0.16; and 95% CI is 0.0, 0.22). The trial did not therefore proceed to the second stage. The median PFS was 2.96 months (95% CI 1.71, 7.66), and the median OS was 13.0 months (95% CI 2.99, 21.52).

Conclusion

In the absence of any objective responses, the use of LuDO as a single agent at the dose schedule used in this study is not recommended for the treatment of neuroblastoma. There are several reasons why this treatment schedule may not have resulted in objective responses, and as other studies do show benefit, the treatment should not be regarded as being of no value. Further trials designed to overcome this schedule’s limitations are required.

Trial registration

ISRCTN98918118; URL: https://www.isrctn.com/search?q=98918118

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Abbreviations

AE:

Adverse event

CT:

Computed tomography

CTCAE:

Common Terminology Criteria for Adverse Events

FDG:

Fluorodeoxyglucose

GaDO:

68-Gallium DOTATATE

GFR:

Glomerular filtration rate

Gy:

Gray

h:

Hour

INRC:

International Neuroblastoma Response Criteria

kg:

Kilogram

kVp:

Kilovoltage peak

l:

Litre

L:

Levo

LuDO:

177-Lutetium DOTATATE

m:

Metre

mA:

Milliamperes

MBq:

Megabecquerel

mIBG:

Meta-iodobenzylguanidine

MRI:

Magnetic resonance imaging

OS:

Overall survival

PET:

Positron emission tomography

PFS:

Progression-free survival

PRRT:

Peptide receptor radionuclide therapy

SAE:

Serious adverse event

SIOPEN:

International Society of Paediatric Oncology European Neuroblastoma clinical research group

SPECT:

Single-photon emission computed tomography

SUVmax :

Maximum standardized uptake value

UK:

United Kingdom

USA:

United States of America

USAN:

United States Adopted Name

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Funding

This trial was funded by the Cancer Research UK (reference C17807/A14091) and Joining Against Cancer in Kids, and supported by researchers at the National Institute for Health Research University College London Hospitals Biomedical Research Centre.

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Author notes

  1. Jennifer E. Gains and Veronica Moroz contributed equally to this work.

Authors and Affiliations

  1. Department of Oncology, University College London Hospitals NHS Foundation Trust, 250 Euston Road, London, NW1 2PG, UK

    Jennifer E. Gains, Matthew D. Aldridge, Connie Peet & Mark N. Gaze

  2. Cancer Research UK Clinical Trials Unit, Institute of Cancer and Genomic Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK

    Veronica Moroz, Keith Wheatley & Jennifer Laidler

  3. Department of Nuclear Medicine, University College London Hospitals NHS Foundation Trust, 235 Euston Road, London, NW1 2BU, UK

    Matthew D. Aldridge, Simon Wan & Jamshed B. Bomanji

Authors
  1. Jennifer E. Gains
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  2. Veronica Moroz
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  4. Simon Wan
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  7. Connie Peet
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  8. Jamshed B. Bomanji
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  9. Mark N. Gaze
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Contributions

Conception and design: Jennifer E. Gains, Veronica Moroz, Matthew D. Aldridge, Jamshed B. Bomanji, Keith Wheatley, Mark N. Gaze

Clinical care of patients: Jennifer E. Gains, Connie Peet, Matthew D. Aldridge, S Wan, Jamshed B. Bomanji, Mark N. Gaze

Collection and assembly of data: Connie Peet, Matthew D. Aldridge, Jennifer Laidler

Data analysis and interpretation: Jennifer E. Gains, Veronica Moroz, Simon Wan, Jamshed B. Bomanji, Matthew D. Aldridge, Keith Wheatley, Mark N. Gaze

Manuscript writing: all authors

Final approval of the manuscript: all authors

Accountable for all aspects of work: all authors

Corresponding author

Correspondence to Mark N. Gaze.

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Gains, J.E., Moroz, V., Aldridge, M.D. et al. A phase IIa trial of molecular radiotherapy with 177-lutetium DOTATATE in children with primary refractory or relapsed high-risk neuroblastoma. Eur J Nucl Med Mol Imaging 47, 2348–2357 (2020). https://doi.org/10.1007/s00259-020-04741-x

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