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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
49
PEGylated recombinant human arginase 1
Women's & Children's Hospital
Adelaide, Australia
Queensland Children's Hospital
Brisbane, Australia
Royal Children's Hospital Melbourne
Melbourne, Australia
Perth Children's Hospital
Perth, Australia
Children's Hospital Westmead
Sydney, Australia
Sydney Children's Hospital
Sydney, Australia
Princes Maxima Centrum
Utrecht, Netherlands
Birmingham Children's Hospital
Birmingham, United Kingdom
Bristol Royal Hospital for Children
Bristol, United Kingdom
Addenbrookes Hospital
Cambridge, United Kingdom
...and 4 more locations
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.
Time frame: 28 days
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
Time frame: After 8 weeks
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
Time frame: 28 days after treatment completion
Disease response - Leukaemia
Disease response ( CR / PR) according to Cheson criteria
Time frame: Within 1 year
Disease response - Sarcoma
Disease response ( CR / PR) according to RECIST criteria
Time frame: Within 1 year
Disease response - High Grade Glioma
Disease response ( CR / PR) according to RANO criteria
Time frame: Within 1 year
Disease response - Neuroblastoma
Disease response ( CR / PR) according to INCR criteria
Time frame: Within 1 year
Progression free survival (PFS)
Time frame: Up to three years after registration
Overall survival (OS).
Time frame: Up to three years after registration
Maximum Plasma Concentration [Cmax], of BCT-100 in the paediatric population.
Time frame: Up to 24 weeks
Time to maximum Plasma Concentration [Tmax], of BCT-100 in the paediatric population.
Time frame: Up to 24 weeks
Minimum Plasma Concentration [Cmin], of BCT-100 in the paediatric population.
Time frame: Up to 24 weeks
Area Under the Curve [AUC], of BCT-100 in the paediatric population.
Time frame: Up to 24 weeks
Duration of adequate arginine depletion in blood.
BCT-100 concentration in blood
Time frame: Up to 24 weeks
Duration of adequate arginine depletion in bone marrow .
BCT-100 concentration in bone marrow
Time frame: Up to 24 weeks
Duration of adequate arginine depletion in cerebrospinal fluid.
BCT-100 concentration in cerebrospinal fluid
Time frame: Up to 24 weeks
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