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 |
| Clinical Trials Information System (CTIS) | 2012-000510-10 |
| Protocol serial number | 13254 |
| Sponsor | University of Birmingham (UK) |
| Funder | Cancer Research UK (UK) Grant Codes: C17807/A14091 |
- 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
Contact information
Miss Jennifer Laidler
Scientific
Scientific
Cancer Research UK Clinical Trials Unit
Institute for Cancer Studies
Edgbaston
Birmingham
B15 2TT
United Kingdom
| ludo@trials.bham.ac.uk |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Non-randomised interventional treatment trial |
| Secondary study design | Non randomised study |
| Study type | Participant 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 |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Lutetium dotatate |
| Primary outcome measure(s) |
Response rate; Timepoint(s): 1 month |
| Key secondary outcome measure(s) |
1. Overall survival; Timepoint(s): Follow up for 5 years |
| Completion date | 01/04/2015 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Child |
| Lower age limit | 18 Months |
| Upper age limit | 18 Years |
| Sex | All |
| Target sample size at registration | 24 |
| 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
- United Kingdom
- England
Study participating centre
Cancer Research UK Clinical Trials Unit
Birmingham
B15 2TT
United Kingdom
B15 2TT
United Kingdom
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/09/2020 | 12/03/2020 | Yes | No |
| Basic results | 21/06/2019 | No | No | ||
| HRA research summary | 28/06/2023 | No | No | ||
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
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.
