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
| ISRCTN | ISRCTN21727048 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN21727048 |
| ClinicalTrials.gov (NCT) | NCT03455140 |
| Clinical Trials Information System (CTIS) | 2017-002762-44 |
| Protocol serial number | 37340 |
| Sponsor | University of Birmingham |
| Funders | Cancer Research UK; Grant Codes: C47669/A24836, Imagine For Margo - Children without Cancer; Grant Codes: ITCC-062 |
- Submission date
- 12/03/2018
- Registration date
- 27/03/2018
- Last edited
- 18/11/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Plain English summary of protocol
Background and study aims
The aim of this study is to assess 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 treatment options are limited with significant side effects. 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 reduce arginine levels and starve cancer cells – a completely new approach. BCT-100 has been tested in adults and has been shown to be active with almost no side effects. This study 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 study will also look at how BCT-100 is broken down in the body and look for new markers of treatment response.
Who can participate?
Children and young adults (aged 1 to 25) with relapsed cancers (leukaemia, neuroblastoma, sarcoma and high-grade gliomas)
What does the study involve?
BCT-100 is given as weekly intravenous infusions (into a vein) over one hour in an outpatient setting. The dose is given at 7-day intervals (+/- 1 day). The dose is increased or decreased based on both safety (side effects) and the successful depletion of arginine in the participants. BCT-100 should at first be given for 8 weeks, i.e. 8 doses, but participants may receive treatment beyond 8 weeks if there is an ongoing clinical benefit.
What are the possible benefits and risks of participating?
This study aims to find the dose which balances high effectiveness with few side effects, and this will then be tested in a larger group. This study will test this drug on four different disease types for relapsed/refractory patients. The options for these patients can be limited and often are associated with a large burden of side effects. BCT-100 has been found to be very well tolerated with few side effects. However, this is the first study involving children.
Where is the study run from?
Hospitals in the UK, Italy, Germany, Netherlands, Spain, Ireland, Denmark and Australia
When is the study starting and how long is it expected to run for?
January 2017 to October 2021
Who is funding the study?
1. Cancer Research UK
2. Imagine For Margo - Children without Cancer
Who is the main contact?
Jodie Hodgson
parc@trials.bham.ac.uk
Contact information
Scientific
Cancer Research UK Clinical Trials Unit (CRCTU)
Institute of Cancer and Genomic Sciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom
| Phone | +44 (0)121 414 9235 |
|---|---|
| parc@trials.bham.ac.uk |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Non-randomized; Interventional; Design type: Treatment, Drug |
| Secondary study design | Non randomised study |
| Study type | Participant information sheet |
| Scientific 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 |
| Study acronym | PARC |
| Study objectives | 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. |
| Ethics approval(s) | Leicester South Research Ethics Committee, 05/03/2018, ref: 18/EM/0024 |
| Health condition(s) or problem(s) studied | Relapsed/refractory cancers of children and young adults |
| Intervention | There is no randomisation for this single-arm trial. BCT-100 is administered as weekly intravenous infusions over one hour which may be administered in an outpatient setting. The dose must be administered at 7-day intervals (+/- 1 day). For phase I the starting dose will be 1600 U/kg and dose escalation/de-escalation is based on both the safety profile (occurrence of DLT) and the successful depletion of arginine in patients. This will establish the phase II recommended dose. BCT-100 should initially be given for 8 weeks, i.e. 8 doses but may receive treatment beyond 8 weeks if there is ongoing clinical benefit. Total trial duration is two years and follow up is minimum one year. |
| Intervention type | Drug |
| Phase | Phase I/II |
| Drug / device / biological / vaccine name(s) | Pegylated recombinant human arginase (BCT-100) |
| Primary outcome measure(s) |
Phase I: the safe and optimal (in terms of arginine depletion) RP2D of BCT-100 as determined by: |
| Key secondary outcome measure(s) |
Current secondary outcome measures as of 02/02/2023: |
| Completion date | 16/10/2022 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Lower age limit | 1 Year |
| Upper age limit | 24 Years |
| Sex | All |
| Target sample size at registration | 64 |
| Total final enrolment | 49 |
| Key inclusion criteria | 1. Aged 1- <25 years old at the time of study registration 2. Histologically confirmed disease in one of the following four groups: 2.1. Group 1 - Acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML) 2.2. Group 2 - Neuroblastoma 2.3. Group 3 - Sarcoma 2.4. Group 4 - High grade glioma (as defined by 2016 WHO CNS classification) 3. Radiological or laboratory evidence of disease progression (during or after completion of first line treatment) or any subsequent recurrence (biopsy at relapse is not mandated) 4. Measurable bone marrow disease (group 1) or at least one evaluable radiological site of disease (group 2, 3 and 4) 5. Adequate liver function defined as a total bilirubin ≤1.5x the upper limit of normal for age and ALT ≤ 3x the upper limit of normal for age 6. Documented negative pregnancy test for female patients of childbearing potential within 7 days of trial entry 7. Sexually active patients must agree to use adequate and appropriate contraception while on study drug and for 12 months following treatment discontinuation 8. Written informed consent given by patient and/or parents/legal representative |
| Key exclusion criteria | 1. Previous treatment with another therapeutic arginine-depleting drug (bacterial or human) or arginase inhibitor 2. Presence of any >= CTCAE grade 3 clinically significant treatment-related toxicity from prior therapies 3. Pregnant or lactating female 4. Evidence of uncontrolled infection |
| Date of first enrolment | 16/04/2018 |
| Date of final enrolment | 01/12/2021 |
Locations
Countries of recruitment
- United Kingdom
- England
- Scotland
- Australia
- Denmark
- Germany
- Ireland
- Italy
- Netherlands
- Spain
Study participating centres
Birmingham
B4 6NH
England
Cambridge
CB2 0QQ
England
Manchester
M13 9WL
England
Sutton
SM2 5PT
England
Bristol
BS2 8BJ
England
Leeds
LS1 3EX
England
Glasgow
G51 4TF
Scotland
Crumlin
Drimnagh
Dublin
D12 V004
Ireland
Parkville
Victoria
3052
Australia
Randwick
Sydney
NSW 2031
Australia
Westmead
Sydney
NSW 2145
Australia
North Adelaide
SA 5006
Australia
Subiaco
Perth
WA 6008
Australia
Utrecht
3584 CS
Netherlands
Results and Publications
| Individual participant data (IPD) Intention to share | Yes |
|---|---|
| IPD sharing plan summary | Available on request |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are/will be available upon request from the Cancer Research UK Clinical Trials Unit (CRCTU) at the University of Birmingham. The (CRCTU) is committed to responsible and controlled sharing of anonymised clinical trial data with the wider research community to maximise potential patient benefit while protecting the privacy and confidentiality of study participants. Participant data and the associated supporting documentation (metadata) will typically be available for all CRCTU clinical trials within 6 months after the publication of the outcome measures unless the trial results are to be used as part of a regulatory submission where release of the data may be delayed or be subject to the approval of a third party. Requests for historical clinical trial data will be dealt with on a case-by-case basis. For trials with long term follow-up, primary outcome data (e.g. response) may be available before secondary outcome data (e.g. survival). Each request will be reviewed independently by the CRCTU Directors in discussion with the Chief Investigator and relevant Trial Management Group and/or independent Trial Steering Committee (as applicable to the trial). In making their decision the Director’s Committee will consider the scientific validity of the request, the qualifications of the research group, the views of the Chief Investigator and trial management and/or steering committees, consent arrangements, the practicality of anonymising the requested data and contractual obligations. Where the CRCTU Directors and appropriate Trial Committees are supportive of the request, and where not already obtained, consent for data transfer will be sought from the Sponsor of the trial before notifying the applicant of the outcome of their request. It is anticipated that applicants will be notified of a decision within 3 months. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | 31/01/2024 | 15/02/2024 | Yes | No | |
| Basic results | version 1.0b | 23/02/2023 | 27/02/2023 | No | No |
| HRA research summary | 26/07/2023 | No | No | ||
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
Additional files
- ISRCTN21727048_BasicResults_V1.0b_23Feb23.pdf
- Basic results
Editorial Notes
18/11/2025: Internal review.
15/02/2024: Publication reference added.
27/02/2023: Basic results corrected.
02/02/2023: The following changes were made to the trial record:
1. The secondary outcome measures were updated.
2. The trial participating centres were updated to add Princess Maxima Center for pediatric oncology and Royal Hospital for Children Glasgow and remove Great Ormond Street Hospital for Children, Rigshospitalet, John Hunter Children’s Hospital, and Lady Cilento Children’s Hospital.
3. Sponsor details updated.
23/01/2023: Basic results and total final enrolment added.
02/12/2020: The following changes were made to the trial record:
1. The recruitment end date was changed from 01/12/2020 to 01/12/2021.
2. The overall trial end date was changed from 16/10/2021 to 16/10/2022.
3. The intention to publish date was changed from 01/07/2022 to 01/07/2023.
4. Contact details updated.
09/07/2020: The trial contact details have been made publicly visible.
24/04/2020: The recruitment end date was changed from 16/04/2020 to 01/12/2020.
12/06/2019: ClinicalTrials.gov number added.
27/03/2019: The condition has been changed from "Specialty: Cancer, Primary sub-specialty: Children's Cancer and Leukaemia; UKCRC code/ Disease: Cancer/ Malignant neoplasms, stated or presumed to be primary, of lymphoid, haematopoietic and related tissue, Cancer/ Malignant neoplasms of thyroid and other endocrine glands, Cancer/ Malignant neoplasms of eye, brain and other parts of central nervous system, Cancer/ Malignant neoplasms of mesothelial and soft tissue" to "Relapsed/refractory cancers of Children and young adults" following a request from the NIHR.
