Plain English Summary
Trial website
Contact information
Type
Scientific
Primary contact
Miss Jennifer Laidler
ORCID ID
Contact details
Cancer Research UK Clinical Trials Unit
Institute for Cancer Studies
Edgbaston
Birmingham
B15 2TT
United Kingdom
-
ludo@trials.bham.ac.uk
Additional identifiers
EudraCT number
2012-000510-10
ClinicalTrials.gov number
Protocol/serial number
13254
Study information
Scientific title
A Phase IIa trial of 177 177 lutetium dotatate in children with primary refractory or relapsed high-risk neuroblastoma
Acronym
LuDo
Study hypothesis
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
London-Hampstead Ethics Board, First MREC approval date 10/10/2012, ref: 12/LO/1422
Study design
Non-randomised interventional treatment trial
Primary study design
Interventional
Secondary study design
Non randomised study
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
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 names
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 trial start date
19/03/2013
Overall trial end date
01/04/2015
Reason abandoned (if study stopped)
Eligibility
Participant 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.
Participant type
Patient
Age group
Child
Gender
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
Participant 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
Recruitment start date
19/03/2013
Recruitment end date
01/04/2015
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Cancer Research UK Clinical Trials Unit
Birmingham
B15 2TT
United Kingdom
Sponsor information
Organisation
University of Birmingham (UK)
Sponsor details
Edgbaston
Birmingham
B15 2TT
United Kingdom
-
ludo@trials.bham.ac.uk
Sponsor type
University/education
Website
Funders
Funder type
Charity
Funder name
Cancer Research UK (UK) Grant Codes: C17807/A14091
Alternative name(s)
CRUK
Funding Body Type
private sector organisation
Funding Body Subtype
other non-profit
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list