A Study Evaluating the Safety and Activity of Pegylated Recombinant Human Arginase (BCT-100)
- Conditions
- CancerPediatric Solid TumorPediatric AMLPediatric ALL
- Interventions
- Drug: PEG- BCT-100
- Registration Number
- NCT03455140
- Lead Sponsor
- University of Birmingham
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 49
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Aged 1- <25 years old at the time of study registration
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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).
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Measurable bone marrow disease (group 1) or at least one evaluable radiological site of disease (group 2, 3 and 4).
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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
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Documented negative pregnancy test for female patients of childbearing potential within 7 days of trial entry
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Sexually active patients must agree to use adequate and appropriate contraception while on study drug and for 12 months following treatment discontinuation
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Written informed consent given by patient and/or parents/legal representative
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group 3 - Sarcomas PEG- BCT-100 PEG- BCT-100 in patients with Sarcomas Starting dose 1600U/Kg IV infusion weekly Group 1 - Leukaemia PEG- BCT-100 PEG- BCT-100 in patients with Leukaemia Starting dose 1600U/Kg IV infusion weekly Group 2 - Neuroblastoma PEG- BCT-100 PEG- BCT-100 in patients with Neuroblastoma Starting dose 1600U/Kg IV infusion weekly Group 4 - High Grade Glioma PEG- BCT-100 PEG- BCT-100 in patients with High Grade Gliomas Starting dose 1600U/Kg IV infusion weekly
- Primary Outcome Measures
Name Time Method 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. After 8 weeks Disease response (Complete Response (CR) or Partial Response (PR)) after 8 weeks of treatment with BCT-100
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 28 days 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.
- Secondary Outcome Measures
Name Time Method Disease response - High Grade Glioma Within 1 year Disease response ( CR / PR) according to RANO criteria
Disease response - Neuroblastoma Within 1 year Disease response ( CR / PR) according to INCR criteria
Progression free survival (PFS) Up to three years after registration Disease response - Sarcoma Within 1 year Disease response ( CR / PR) according to RECIST criteria
The incidence and severity of Adverse Events (AEs) as Assessed by CTCAE v4 28 days after treatment completion Incidence and severity of Adverse Events (AEs) defined by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v4
Disease response - Leukaemia Within 1 year Disease response ( CR / PR) according to Cheson criteria
Overall survival (OS). Up to three years after registration Maximum Plasma Concentration [Cmax], of BCT-100 in the paediatric population. Up to 24 weeks Time to maximum Plasma Concentration [Tmax], of BCT-100 in the paediatric population. Up to 24 weeks Minimum Plasma Concentration [Cmin], of BCT-100 in the paediatric population. Up to 24 weeks Area Under the Curve [AUC], of BCT-100 in the paediatric population. Up to 24 weeks Duration of adequate arginine depletion in blood. Up to 24 weeks BCT-100 concentration in blood
Duration of adequate arginine depletion in bone marrow . Up to 24 weeks BCT-100 concentration in bone marrow
Duration of adequate arginine depletion in cerebrospinal fluid. Up to 24 weeks BCT-100 concentration in cerebrospinal fluid
Trial Locations
- Locations (14)
Royal Marsden Hospital
🇬🇧Sutton, United Kingdom
Royal Manchester Children's Hospital
🇬🇧Manchester, United Kingdom
Perth Children's Hospital
🇦🇺Perth, Australia
Queensland Children's Hospital
🇦🇺Brisbane, Australia
Women's & Children's Hospital
🇦🇺Adelaide, Australia
Royal Children's Hospital Melbourne
🇦🇺Melbourne, Australia
Children's Hospital Westmead
🇦🇺Sydney, Australia
Sydney Children's Hospital
🇦🇺Sydney, Australia
Addenbrookes Hospital
🇬🇧Cambridge, United Kingdom
Princes Maxima Centrum
🇳🇱Utrecht, Netherlands
Birmingham Children's Hospital
🇬🇧Birmingham, United Kingdom
Bristol Royal Hospital for Children
🇬🇧Bristol, United Kingdom
Leeds Children's Hospital
🇬🇧Leeds, United Kingdom
Royal Hospital for Children
🇬🇧Glasgow, United Kingdom