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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03455140


Additional trial details provided through ANZCTR are available at the end of this record.


Registration number
NCT03455140
Ethics application status
Date submitted
1/02/2018
Date registered
6/03/2018
Date last updated
25/03/2020

Titles & IDs
Public title
A Study Evaluating the Safety and Activity of Pegylated Recombinant Human Arginase (BCT-100)
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
Secondary ID [1] 0 0
RG_16-040
Universal Trial Number (UTN)
Trial acronym
PARC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cancer 0 0
Pediatric Solid Tumor 0 0
Pediatric AML 0 0
Pediatric ALL 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - PEG- BCT-100

Experimental: Group 1 - Leukaemia - PEG- BCT-100 in patients with Leukaemia Starting dose 1600U/Kg IV infusion weekly

Experimental: Group 2 - Neuroblastoma - PEG- BCT-100 in patients with Neuroblastoma Starting dose 1600U/Kg IV infusion weekly

Experimental: Group 3 - Sarcomas - PEG- BCT-100 in patients with Sarcomas Starting dose 1600U/Kg IV infusion weekly

Experimental: Group 4 - High Grade Glioma - PEG- BCT-100 in patients with High Grade Gliomas Starting dose 1600U/Kg IV infusion weekly


Treatment: Drugs: PEG- BCT-100
PEGylated recombinant human arginase 1

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase I: to establish the recommended phase II dose (RP2D) of BCT-100 in children and young adults as assessed by dose limiting toxicity (DLT) and complete arginine depletion - Safety profile as measured by the occurrence/non-occurrence of DLT within 28 days of treatment with BCT-100.
o Optimal dose as measured by the complete depletion of arginine. This is defined as AAD <8µM arginine in the blood after 3 doses of BCT-100.
Timepoint [1] 0 0
28 days
Primary outcome [2] 0 0
Phase II: to determine the activity of single agent BCT-100 against relapsed/refractory leukaemia, neuroblastoma, sarcoma and high grade glioma in children and young adults as measured by disease response after 8 weeks. - Disease response (Complete Response (CR) or Partial Response (PR)) after 8 weeks of treatment with BCT-100
Timepoint [2] 0 0
After 8 weeks
Secondary outcome [1] 0 0
The incidence and severity of Adverse Events (AEs) as Assessed by CTCAE v4 - Incidence and severity of Adverse Events (AEs) defined by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v4
Timepoint [1] 0 0
28 days after treatment completion
Secondary outcome [2] 0 0
Disease response - Leukaemia - Disease response ( CR / PR) according to Cheson criteria
Timepoint [2] 0 0
Within 1 year
Secondary outcome [3] 0 0
Disease response - Sarcoma - Disease response ( CR / PR) according to RECIST criteria
Timepoint [3] 0 0
Within 1 year
Secondary outcome [4] 0 0
Disease response - High Grade Glioma - Disease response ( CR / PR) according to RANO criteria
Timepoint [4] 0 0
Within 1 year
Secondary outcome [5] 0 0
Disease response - Neuroblastoma - Disease response ( CR / PR) according to INCR criteria
Timepoint [5] 0 0
Within 1 year
Secondary outcome [6] 0 0
Progression free survival (PFS)
Timepoint [6] 0 0
Up to three years after registration
Secondary outcome [7] 0 0
Overall survival (OS).
Timepoint [7] 0 0
Up to three years after registration
Secondary outcome [8] 0 0
Maximum Plasma Concentration [Cmax], of BCT-100 in the paediatric population.
Timepoint [8] 0 0
Up to 24 weeks
Secondary outcome [9] 0 0
Time to maximum Plasma Concentration [Tmax], of BCT-100 in the paediatric population.
Timepoint [9] 0 0
Up to 24 weeks
Secondary outcome [10] 0 0
Minimum Plasma Concentration [Cmin], of BCT-100 in the paediatric population.
Timepoint [10] 0 0
Up to 24 weeks
Secondary outcome [11] 0 0
Area Under the Curve [AUC], of BCT-100 in the paediatric population.
Timepoint [11] 0 0
Up to 24 weeks
Secondary outcome [12] 0 0
Duration of adequate arginine depletion in blood. - BCT-100 concentration in blood
Timepoint [12] 0 0
Up to 24 weeks
Secondary outcome [13] 0 0
Duration of adequate arginine depletion in bone marrow . - BCT-100 concentration in bone marrow
Timepoint [13] 0 0
Up to 24 weeks
Secondary outcome [14] 0 0
Duration of adequate arginine depletion in cerebrospinal fluid. - BCT-100 concentration in cerebrospinal fluid
Timepoint [14] 0 0
Up to 24 weeks

Eligibility
Key inclusion criteria
- Aged 1- <25 years old at the time of study registration

- Histologically confirmed disease in one of the following four groups:

- Group 1 - Acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML)

- Group 2 - Neuroblastoma Group 3 - Sarcoma

- Group 4 - High grade glioma (as defined by 2016 WHO CNS classification)

- 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).

- Measurable bone marrow disease (group 1) or at least one evaluable radiological site
of disease (group 2, 3 and 4).

- 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

- Documented negative pregnancy test for female patients of childbearing potential
within 7 days of trial entry

- Sexually active patients must agree to use adequate and appropriate contraception
while on study drug and for 12 months following treatment discontinuation

- Written informed consent given by patient and/or parents/legal representative
Minimum age
1 Year
Maximum age
25 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Previous treatment with another therapeutic arginine depleting drug (bacterial or
human) or arginase inhibitor

- Presence of any = CTCAE grade 3 clinically significant treatment-related toxicity from
prior therapies

- Pregnant or lactating female

- Evidence of uncontrolled infection

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1/Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Women's & Children's Hospital - Adelaide
Recruitment postcode(s) [1] 0 0
- Adelaide
Recruitment outside Australia
Country [1] 0 0
United Kingdom
State/province [1] 0 0
Birmingham
Country [2] 0 0
United Kingdom
State/province [2] 0 0
Bristol
Country [3] 0 0
United Kingdom
State/province [3] 0 0
Cambridge
Country [4] 0 0
United Kingdom
State/province [4] 0 0
Glasgow
Country [5] 0 0
United Kingdom
State/province [5] 0 0
Leeds
Country [6] 0 0
United Kingdom
State/province [6] 0 0
Manchester
Country [7] 0 0
United Kingdom
State/province [7] 0 0
Sutton

Funding & Sponsors
Primary sponsor type
Other
Name
University of Birmingham
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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 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
with relapsed cancers will be recruited over 2 years.
Trial website
https://clinicaltrials.gov/show/NCT03455140
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Francis J Mussai, DPhil
Address 0 0
University of Birmingham
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Nicola Fenwick, BMedSc
Address 0 0
Country 0 0
Phone 0 0
+44 121 415 8782
Fax 0 0
Email 0 0
n.fenwick@bham.ac.uk
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03455140

Additional trial details provided through ANZCTR
Accrual to date
Recruiting in Australia
Recruitment state(s)
SA
Funding & Sponsors
Primary sponsor
Primary sponsor name
Primary sponsor address
Primary sponsor country
Secondary sponsor category [1] 32
Other Collaborative groups
Name [1] 32
ANZCHOG
Address [1] 32
27-31 Wright Street, Clayton VIC 3168
Country [1] 32
Australia
Ethics approval
Ethics application status
 
Public notes
Women's and Children's Hospital

Contacts
Principal investigator
Title 157 0
Dr
Name 157 0
Maria Kirby
Address 157 0
72 King William Rd, North Adelaide SA 5006
Country 157 0
Australia
Phone 157 0
+618 8161 7411
Fax 157 0
Email 157 0
Maria.Kirby@sa.gov.au
Contact person for public queries
Title 158 0
Mrs
Name 158 0
Robyn Strong
Address 158 0
27-31 Wright Street, Clayton VIC 3168
Country 158 0
Australia
Phone 158 0
+613 8572 2684
Fax 158 0
Email 158 0
Robyn.Strong@hudson.org.au
Contact person for scientific queries
Title 159 0
Dr
Name 159 0
Maria Kirby
Address 159 0
72 King William Rd, North Adelaide SA 5006
Country 159 0
Australia
Phone 159 0
+618 8161 7411
Fax 159 0
Email 159 0
Maria.Kirby@sa.gov.au