Condition category
Cancer
Date applied
20/12/2013
Date assigned
20/12/2013
Last edited
06/02/2014
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

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 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 (1) the toxicity and (2) the efficacy of 177Lu DOTATATE in children with relapsed or refractory high-risk neuroblastoma. Secondary, translational, aims are (1) to investigate 68Ga DOTATATE PET/CT for imaging of neuroblastoma, in comparison with the standard of 123I-mIBG, (2) to assess the relationship between the expression of somatostatin receptors measured by immunohistochemistry in archived neuroblastoma tissue from each patient with their imaging, and (3) 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.

More details can be found at: http://public.ukcrn.org.uk/search/StudyDetail.aspx?StudyID=13254

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 controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below 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

Other

Phase

Phase II

Drug names

Primary outcome measures

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

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

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes