A study of 177 lutetium dotatate in children with primary refractory or relapsed high-risk neuroblastoma

ISRCTN	ISRCTN98918118
DOI	https://doi.org/10.1186/ISRCTN98918118
EudraCT/CTIS number	2012-000510-10
Secondary identifying numbers	13254

Submission date: 20/12/2013
Registration date: 20/12/2013
Last edited: 12/03/2020

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

http://www.cancerresearchuk.org/cancer-help/trials/a-trial-looking-177-lutetium-dotatate-neuroblastoma-children-young-people-ludo?

Contact information

Miss Jennifer Laidler
Scientific

Cancer Research UK Clinical Trials Unit
Institute for Cancer Studies
Edgbaston
Birmingham
B15 2TT
United Kingdom

Email	ludo@trials.bham.ac.uk

Study information

Study design	Non-randomised interventional treatment trial
Primary study design	Interventional
Secondary study design	Non randomised study
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details to request a patient information sheet
Scientific title	A Phase IIa trial of 177 177 lutetium dotatate in children with primary refractory or relapsed high-risk neuroblastoma
Study acronym	LuDo
Study objectives	High-risk neuroblastoma is a common childhood cancer. Initial standard chemotherapy treatment produces responses in about two thirds of patients, many of whom will later relapse. The others have primary refractory disease. Overall cure rates are low, and so effective new treatments are needed. Many neuroblastoma cells express somatostatin receptors. Radiolabelled octreotide analogues can be used for nuclear medicine imaging and therapy of somatostatin receptor positive tumours. 68Ga DOTATATE and 177Lu DOTATATE have been shown to be effective octreotide analogues for imaging and treatment respectively of neuroendocrine cancers in adults. The primary aims of this study are to evaluate the toxicity and the efficacy of 177Lu DOTATATE in children with relapsed or refractory high-risk neuroblastoma. Secondary, translational, aims are to investigate 68Ga DOTATATE PET/CT for imaging of neuroblastoma, in comparison with the standard of 123I-mIBG, to assess the relationship between the expression of somatostatin receptors measured by immunohistochemistry in archived neuroblastoma tissue from each patient with their imaging, and to correlate tumour radiation dosimetry with response. This will be a Phase II clinical trial using a Simon Two Stage Minimax design. This requires 14 patients in Stage 1. If three or more responses are seen, another 10 patients will be recruited in Stage 2. If eight or more responses are seen in these 24 patients, then the treatment will be deemed worthy of further investigation in this patient group.
Ethics approval(s)	London-Hampstead Ethics Board, First MREC approval date 10/10/2012, ref: 12/LO/1422
Health condition(s) or problem(s) studied	Topic: National Cancer Research Network; Subtopic: Paediatric Oncology; Disease: Brain and Nervous System
Intervention	177Lutetium DOTATATE: The investigational medicinal product (IMP) for the study. Patients will receive up to a maximum of 4 administrations 8 weeks apart. 68Ga DOTATATE PET/CT: Potential patients for this study will require a 68Ga DOTATATE PET/CT to assess eligibility. Uptake in the tumour at least as high as the uptake in the liver must be demonstrated for a patient to be eligible. Amino acid solution infusion: An amino acid solution is infused over 4 hours concurrently with the radionuclide administration to reduce renal tubular uptake and minimise nephrotoxicity. SPECT/CT dosimetry: In radionuclide therapy there is an uncertain relationship between the administered activity (in GBq) of the drug and the absorbed dose (in Gray). Therefore following administration whole body and SPECT/CT dosimetry will be performed to accurately determine the dose received by the whole body, bone marrow, kidneys and the tumour. Whole blood profile: Weekly bloods will be taken to perform assessment of haematological toxicity Study Entry : Registration only
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Lutetium dotatate
Primary outcome measure	Response rate; Timepoint(s): 1 month
Secondary outcome measures	1. Overall survival; Timepoint(s): Follow up for 5 years 2. Progression-free survival; Timepoint(s): Follow up for 5 years 3. Toxic effects
Overall study start date	19/03/2013
Completion date	01/04/2015

Eligibility

Participant type(s)	Patient
Age group	Child
Lower age limit	18 Months
Upper age limit	18 Years
Sex	Both
Target number of participants	Planned Sample Size: 24; UK Sample Size: 24; Description: 14 patients to be treated in stage 1 and a further 10 patients to be enrolled in stage 2 with a total of 24 patients
Total final enrolment	21
Key inclusion criteria	1. Histologically confirmed diagnosis of neuroblastoma 2. Relapsed or primary refractory high-risk neuroblastoma (International Neuroblastoma Staging System stage 4 or International Neuroblastoma Risk Group staging System M) 3. Age >18 months and <18 years of age at the time of enrolment into the study 4. Life expectancy of greater than 3 months 5. Performance Status: 5.1. Karnofsky 50% or more (for patients >12 years of age) 5.2. Lansky 50% or more (for patients <12 years of age) 5.3. Adequate recovery from major surgery prior to receiving study treatment 5.4. Uptake in primary tumour or metastatic tumour deposits on 68Gallium DOTATATE PET/CT at least as high as the liver uptake and performed within a month prior to trial 5.5. IMIBG and FDG PET/CT within a month prior to trial entry 5.6. Two-week washout from any prior treatment 5.7. Patients must have recovery of hematological toxicity following previous therapy 6. Laboratory requirements within 7 days of commencement of therapy 6.1. Absolute neutrophil count > 1.0 x 10^9/L 6.2. Absolute platelets > 100 x 10^9/L 7. Biochemistry: 7.1. Bilirubin within normal range 7.2. ALT within 2.5 x ULN 7.3. ALP within 5 x ULN 7.4. Glomerular filtration rate >50 mL/min/1.73m2 8. Before patient registration, written informed consent 9. Parents or other appropriate adult to sign the local Comforters and Carers consent before patient registration 10. Agreed to a follow-up of 5 years.
Key exclusion criteria	1. Not fit enough to undergo proposed study treatment 2. Concurrent treatment with any antitumour agents 3. Prior treatment with other radiolabelled somatostatin analogues 4. Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient or legal guardian before registration in the trial
Date of first enrolment	19/03/2013
Date of final enrolment	01/04/2015

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Cancer Research UK Clinical Trials Unit

Birmingham
B15 2TT
United Kingdom

Sponsor information

University of Birmingham (UK)
University/education

Edgbaston
Birmingham
B15 2TT
England
United Kingdom

Email	ludo@trials.bham.ac.uk
"ROR"	https://ror.org/03angcq70

Funders

Funder type

Charity

Cancer Research UK (UK) Grant Codes: C17807/A14091
Private sector organisation / Other non-profit organizations

Alternative name(s): CR_UK, Cancer Research UK - London, CRUK
Location: United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Basic results			21/06/2019	No	No
Results article	results	01/09/2020	12/03/2020	Yes	No
HRA research summary			28/06/2023	No	No

Editorial Notes

12/03/2020: Publication reference added.
21/06/2019: Added clinicaltrialsregister.eu link to basic results (scientific). Added total final enrollment.
06/07/2017: No publications found, verifying study status with principal investigator.