PARC
Research type
Research Study
Full title
A phase I/II study evaluating the safety and activity of Pegylated recombinant human Arginase (BCT-100) in Relapsed/refractory cancers of Children and young adults
IRAS ID
232898
Contact name
Francis Mussai
Contact email
Sponsor organisation
University of Birmingham
Eudract number
2017-002762-44
Clinicaltrials.gov Identifier
ITCC-062, ITCC
Duration of Study in the UK
3 years, 6 months, 14 days
Research summary
Research Summary
PARC is an international phase I/II trial evaluating the safety and activity of pegylated recombinant human arginase (BCT-100) in children and young people with relapsed/refractory leukaemia, neuroblastoma, sarcoma and high grade gliomas (brain cancers).
Currently the outcomes for these patients are poor and the therapeutic options are limited with a significant toxicity burden. Therefore new treatments which work in different ways to standard chemotherapy are urgently needed.
Research has shown that arginine (a nutrient) is important in the survival of cancer cells. BCT-100 is a drug which can deplete arginine levels and starve cancer cells – a completely new approach. BCT-100 has been tested in adults and shown to be active with almost no side-effects. This trial will test whether this dose of BCT-100 is also safe and active in children and young adults with relapsed/refractory leukaemia, neuroblastoma, sarcoma and high grade glioma. The trial will also study how BCT-100 is broken down in the body and look for new biological markers of treatment response. Up to 64 children and young adults with relapsed cancers will be recruited over 2 years.Summary of Results
As cancers grow they use nutrients to help the cells survive. Laboratory data shows that a nutrient called ‘arginine’ is taken up by cancer cells to allow them to grow and divide.
These cancer cells rely on arginine as they cannot make their own due to changes inside the cells.In the PARC trial doctors tested a drug called BCT-100, which can reduce the amount of arginine in the body to very low levels – starving cancer of this nutrient, causing the cancer cells die. Normal cells appear to be unaffected as they can make their own arginine to compensate.
The trial was open to children with one of the following relapsed cancers (blood cancers/leukaemias), neuroblastoma (a solid cancer of the nerves), sarcomas (cancers of muscle and connective tissues), or high grade gliomas (brain tumours).
The trial was composed of 2 parts: the first (Phase 1) is to decide which dose of BCT-100 is safe to give and the second part (Phase II) is to test whether BCT-100 helps children with relapsed cancer. The aim was to recruit 13 patients in each group.
Scientists measured the effect of the drug on arginine, on the cancer, and work out why some patients respond/ do not respond.
The trial recruited 49 patients over 4 years from three countries: the UK (41), Australia (4) and The Netherlands (4). Of which 45 patients started treatment and were evaluable for analysis: 7 leukaemia, 12 neuroblastoma, 13 sarcoma and 13 high grade gliomas. Recruitment to the leukaemia group proved challenging due to a lack of eligible patients and competing clinical studies. Therefore the study closed prior to completing recruitment to this group.
The Phase 1 part of the study demonstrated that BCT-100 can be administered to children with relapsed/refractory cancers safely with a low level of side effects. A dose of 1600U/kg of BCT-100, given weekly via a one-hour intravenous infusion, was chosen because it was both safe and sufficiently reduced arginine levels. This is the same dose that has been shown to be safe and effective at reducing arginine levels in adults.
The Phase II part of the study was designed to look at whether a patient’s cancer responded to BCT-100 treatment when looked at using radiological scans after 8 weeks of treatment. Although no patients exhibited a complete remission, 1 patient with a high grade glioma experienced a partial response. In addition, 8 patients maintained stable disease (1 leukaemia, 3 neuroblastoma, 3 sarcoma and 1 high grade glioma). 8 patients remained on treatment beyond the initial 8 weeks (range: 10-68 weeks).
Overall, the data from the study suggest that BCT-100 can slow the growth of cancers with a low side effect profile. This provides the basis of exploring the use of BCT-100 in combination with other cancer treatments, especially in paediatric cancers which may be more sensitive to a reduction arginine levels.
The analysis of samples taken from patients during their participation in PARC is ongoing and we hope that this will help further identify patients and cancer types that may benefit from treatment with BCT100.
We would like to thank all the patients and parents who participated in the PARC study.
REC name
East Midlands - Leicester South Research Ethics Committee
REC reference
18/EM/0024
Date of REC Opinion
1 Mar 2018
REC opinion
Further Information Favourable Opinion