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

Cancer Clinical Trial

— PARC  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03455140
• Other study ID #: RG_16-040
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: August 28, 2018
• Est. completion date: July 22, 2022

Study information

• Verified date: September 2022
• Source: University of Birmingham
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: July 22, 2022
• Est. primary completion date: July 22, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 25 Years

Eligibility

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

Related Conditions & MeSH terms

• Cancer
• Pediatric ALL
• Pediatric AML
• Pediatric Solid Tumor

Intervention

Drug:
• PEG- BCT-100
PEGylated recombinant human arginase 1

Locations

Country	Name	City	State
Australia	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
Netherlands	Princes Maxima Centrum	Utrecht
United Kingdom	Birmingham Children's Hospital	Birmingham
United Kingdom	Bristol Royal Hospital for Children	Bristol
United Kingdom	Addenbrookes Hospital	Cambridge
United Kingdom	Royal Hospital for Children	Glasgow
United Kingdom	Leeds Children's Hospital	Leeds
United Kingdom	Royal Manchester Children's Hospital	Manchester
United Kingdom	Royal Marsden Hospital	Sutton

Sponsors (1)

Lead Sponsor	Collaborator
University of Birmingham

Countries where clinical trial is conducted

Australia,  Netherlands,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	Disease response - Leukaemia	Disease response ( CR / PR) according to Cheson criteria	Within 1 year
Secondary	Disease response - Sarcoma	Disease response ( CR / PR) according to RECIST criteria	Within 1 year
Secondary	Disease response - High Grade Glioma	Disease response ( CR / PR) according to RANO criteria	Within 1 year
Secondary	Disease response - Neuroblastoma	Disease response ( CR / PR) according to INCR criteria	Within 1 year
Secondary	Progression free survival (PFS)		Up to three years after registration
Secondary	Overall survival (OS).		Up to three years after registration
Secondary	Maximum Plasma Concentration [Cmax], of BCT-100 in the paediatric population.		Up to 24 weeks
Secondary	Time to maximum Plasma Concentration [Tmax], of BCT-100 in the paediatric population.		Up to 24 weeks
Secondary	Minimum Plasma Concentration [Cmin], of BCT-100 in the paediatric population.		Up to 24 weeks
Secondary	Area Under the Curve [AUC], of BCT-100 in the paediatric population.		Up to 24 weeks
Secondary	Duration of adequate arginine depletion in blood.	BCT-100 concentration in blood	Up to 24 weeks
Secondary	Duration of adequate arginine depletion in bone marrow .	BCT-100 concentration in bone marrow	Up to 24 weeks
Secondary	Duration of adequate arginine depletion in cerebrospinal fluid.	BCT-100 concentration in cerebrospinal fluid	Up to 24 weeks