A Study Evaluating the Safety and Activity of Pegylated Recombinant Human Arginase (BCT-100) (PARC)

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

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 Overview

• Status: Completed
• Conditions: Cancer; Pediatric ALL; Pediatric Solid Tumor; Pediatric AML
• Intervention / Treatment: Drug: PEG- BCT-100

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • Adelaide, Australia
    • Women's & Children's Hospital
  • Brisbane, Australia
    • Queensland CHILDREN'S HOSPITAL
  • Melbourne, Australia
    • Royal Children's Hospital Melbourne
  • Perth, Australia
    • Perth Children's Hospital
  • Sydney, Australia
    • Children's Hospital Westmead
  • Sydney, Australia
    • Sydney Children's Hospital
• Netherlands
  • Utrecht, Netherlands
    • Princes Maxima Centrum
• United Kingdom
  • Birmingham, United Kingdom
    • Birmingham Children's Hospital
  • Bristol, United Kingdom
    • Bristol Royal Hospital for Children
  • Cambridge, United Kingdom
    • Addenbrookes Hospital
  • Glasgow, United Kingdom
    • Royal Hospital for Children
  • Leeds, United Kingdom
    • Leeds Children's Hospital
  • Manchester, United Kingdom
    • Royal Manchester Children's Hospital
  • Sutton, United Kingdom
    • Royal Marsden Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 months to 23 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1 - Leukaemia; PEG- BCT-100 in patients with Leukaemia Starting dose 1600U/Kg IV infusion weekly	Drug: PEG- BCT-100; PEGylated recombinant human arginase 1; Other Names: rhArg1peg5000
Experimental: Group 2 - Neuroblastoma; PEG- BCT-100 in patients with Neuroblastoma Starting dose 1600U/Kg IV infusion weekly	Drug: PEG- BCT-100; PEGylated recombinant human arginase 1; Other Names: rhArg1peg5000
Experimental: Group 3 - Sarcomas; PEG- BCT-100 in patients with Sarcomas Starting dose 1600U/Kg IV infusion weekly	Drug: PEG- BCT-100; PEGylated recombinant human arginase 1; Other Names: rhArg1peg5000
Experimental: Group 4 - High Grade Glioma; PEG- BCT-100 in patients with High Grade Gliomas Starting dose 1600U/Kg IV infusion weekly	Drug: PEG- BCT-100; PEGylated recombinant human arginase 1; Other Names: rhArg1peg5000

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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	After 8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	28 days after treatment completion
Disease response - Leukaemia	Disease response ( CR / PR) according to Cheson criteria	Within 1 year
Disease response - Sarcoma	Disease response ( CR / PR) according to RECIST criteria	Within 1 year
Disease response - High Grade Glioma	Disease response ( CR / PR) according to RANO criteria	Within 1 year
Disease response - Neuroblastoma	Disease response ( CR / PR) according to INCR criteria	Within 1 year
Progression free survival (PFS)		Up to three years after registration
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.	BCT-100 concentration in blood	Up to 24 weeks
Duration of adequate arginine depletion in bone marrow .	BCT-100 concentration in bone marrow	Up to 24 weeks
Duration of adequate arginine depletion in cerebrospinal fluid.	BCT-100 concentration in cerebrospinal fluid	Up to 24 weeks

Collaborators and Investigators

• Sponsor: University of Birmingham
• Investigators: Study Chair: Francis J Mussai, DPhil, University of Birmingham

Study record dates

Study Major Dates

• Study Start (Actual): August 28, 2018
• Primary Completion (Actual): July 22, 2022
• Study Completion (Actual): July 22, 2022

Study Registration Dates

• First Submitted: February 1, 2018
• First Submitted That Met QC Criteria: February 27, 2018
• First Posted (Actual): March 6, 2018

Study Record Updates

• Last Update Posted (Actual): September 2, 2022
• Last Update Submitted That Met QC Criteria: September 1, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Children; Arginine; Young Adult; Arginase
• Additional Relevant MeSH Terms: Antineoplastic Agents; BCT-100
• Other Study ID Numbers: RG_16-040

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No