Clinical trial NCT03455140: A Study Evaluating the Safety and Activity of Pegylated Recombinant Human Arginase (BCT-100)
Official 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Cancer
Pediatric Solid Tumor
Pediatric AML
Pediatric ALL
Keywords: Arginine
Arginase
Children
Young Adult
Lead sponsor: University of Birmingham
Sponsor class: OTHER
First posted: 2018-03-06
Enrollment: 49
Sex: ALL
Minimum age (years): 1
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

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

Primary outcomes:
measure: 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
timeFrame: 28 days
measure: 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.
timeFrame: After 8 weeks
Secondary outcomes:
measure: The incidence and severity of Adverse Events (AEs) as Assessed by CTCAE v4
timeFrame: 28 days after treatment completion
measure: Disease response - Leukaemia
timeFrame: Within 1 year
measure: Disease response - Sarcoma
timeFrame: Within 1 year
measure: Disease response - High Grade Glioma
timeFrame: Within 1 year
measure: Disease response - Neuroblastoma
timeFrame: Within 1 year
measure: Progression free survival (PFS)
timeFrame: Up to three years after registration
measure: Overall survival (OS).
timeFrame: Up to three years after registration
measure: Maximum Plasma Concentration [Cmax], of BCT-100 in the paediatric population.
timeFrame: Up to 24 weeks
measure: Time to maximum Plasma Concentration [Tmax], of BCT-100 in the paediatric population.
timeFrame: Up to 24 weeks
measure: Minimum Plasma Concentration [Cmin], of BCT-100 in the paediatric population.
timeFrame: Up to 24 weeks
measure: Area Under the Curve [AUC], of BCT-100 in the paediatric population.
timeFrame: Up to 24 weeks
measure: Duration of adequate arginine depletion in blood.
timeFrame: Up to 24 weeks
measure: Duration of adequate arginine depletion in bone marrow .
timeFrame: Up to 24 weeks
measure: Duration of adequate arginine depletion in cerebrospinal fluid.
timeFrame: Up to 24 weeks
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: Women's & Children's Hospital
city: Brisbane
country: Australia
facility: Queensland Children's Hospital
city: Melbourne
country: Australia
facility: Royal Children's Hospital Melbourne
city: Perth
country: Australia
facility: Perth Children's Hospital
city: Sydney
country: Australia
facility: Children's Hospital Westmead
city: Sydney
country: Australia
facility: Sydney Children's Hospital
city: Utrecht
country: Netherlands
facility: Princes Maxima Centrum
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital
city: Bristol
country: United Kingdom
facility: Bristol Royal Hospital for Children
city: Cambridge
country: United Kingdom
facility: Addenbrookes Hospital
city: Glasgow
country: United Kingdom
facility: Royal Hospital for Children
city: Leeds
country: United Kingdom
facility: Leeds Children's Hospital
city: Manchester
country: United Kingdom
facility: Royal Manchester Children's Hospital
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital
Study officials:
affiliation: University of Birmingham
name: Francis J Mussai, DPhil
role: STUDY_CHAIR
References: