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

September 1, 2022 updated by: University of Birmingham

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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
49

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

2 years to 21 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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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
Time Frame: 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.
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.
Time Frame: 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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
The incidence and severity of Adverse Events (AEs) as Assessed by CTCAE v4
Time Frame: 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
28 days after treatment completion
Disease response - Leukaemia
Time Frame: Within 1 year
Disease response ( CR / PR) according to Cheson criteria
Within 1 year
Disease response - Sarcoma
Time Frame: Within 1 year
Disease response ( CR / PR) according to RECIST criteria
Within 1 year
Disease response - High Grade Glioma
Time Frame: Within 1 year
Disease response ( CR / PR) according to RANO criteria
Within 1 year
Disease response - Neuroblastoma
Time Frame: Within 1 year
Disease response ( CR / PR) according to INCR criteria
Within 1 year
Progression free survival (PFS)
Time Frame: Up to three years after registration
Up to three years after registration
Overall survival (OS).
Time Frame: Up to three years after registration
Up to three years after registration
Maximum Plasma Concentration [Cmax], of BCT-100 in the paediatric population.
Time Frame: Up to 24 weeks
Up to 24 weeks
Time to maximum Plasma Concentration [Tmax], of BCT-100 in the paediatric population.
Time Frame: Up to 24 weeks
Up to 24 weeks
Minimum Plasma Concentration [Cmin], of BCT-100 in the paediatric population.
Time Frame: Up to 24 weeks
Up to 24 weeks
Area Under the Curve [AUC], of BCT-100 in the paediatric population.
Time Frame: Up to 24 weeks
Up to 24 weeks
Duration of adequate arginine depletion in blood.
Time Frame: Up to 24 weeks
BCT-100 concentration in blood
Up to 24 weeks
Duration of adequate arginine depletion in bone marrow .
Time Frame: Up to 24 weeks
BCT-100 concentration in bone marrow
Up to 24 weeks
Duration of adequate arginine depletion in cerebrospinal fluid.
Time Frame: Up to 24 weeks
BCT-100 concentration in cerebrospinal fluid
Up to 24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Birmingham

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Francis J Mussai, DPhil, University of Birmingham

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 28, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 22, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 22, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 1, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 27, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 6, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 2, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 1, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Cancer

Clinical Trials on PEG- BCT-100

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings