Skip to main content
OpenTrials
Completed

NCT Number: NCT03455140

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

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Cancer Hematologic Diseases Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Leukemia Leukemia, Lymphoid Lymphatic Diseases Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type Pediatric ALL Pediatric AML Pediatric Solid Tumor Precursor Cell Lymphoblastic Leukemia-Lymphoma

Age range

1 year–25 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Women's & Children's Hospital, Adelaide, Australia

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

PEG- BCT-100

Drug

PEGylated recombinant human arginase 1

Other names: rhArg1peg5000

Primary outcomes

  1. 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.

  2. 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

Secondary outcomes

  1. 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

  2. Disease response - Leukaemia

    Time frame: Within 1 year

    Disease response ( CR / PR) according to Cheson criteria

  3. Disease response - Sarcoma

    Time frame: Within 1 year

    Disease response ( CR / PR) according to RECIST criteria

  4. Disease response - High Grade Glioma

    Time frame: Within 1 year

    Disease response ( CR / PR) according to RANO criteria

  5. Disease response - Neuroblastoma

    Time frame: Within 1 year

    Disease response ( CR / PR) according to INCR criteria

  6. Progression free survival (PFS)

    Time frame: Up to three years after registration

  7. Overall survival (OS).

    Time frame: Up to three years after registration

  8. Maximum Plasma Concentration [Cmax], of BCT-100 in the paediatric population.

    Time frame: Up to 24 weeks

  9. Time to maximum Plasma Concentration [Tmax], of BCT-100 in the paediatric population.

    Time frame: Up to 24 weeks

  10. Minimum Plasma Concentration [Cmin], of BCT-100 in the paediatric population.

    Time frame: Up to 24 weeks

  11. Area Under the Curve [AUC], of BCT-100 in the paediatric population.

    Time frame: Up to 24 weeks

  12. Duration of adequate arginine depletion in blood.

    Time frame: Up to 24 weeks

    BCT-100 concentration in blood

  13. Duration of adequate arginine depletion in bone marrow .

    Time frame: Up to 24 weeks

    BCT-100 concentration in bone marrow

  14. Duration of adequate arginine depletion in cerebrospinal fluid.

    Time frame: Up to 24 weeks

    BCT-100 concentration in cerebrospinal fluid

Sponsors and collaborators

Lead sponsor

University of Birmingham

Other

Registry information

Official study 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

Acronym: PARC

Important dates

Study start
2018
Primary completion
2022
Study completion
2022
First posted
Mar 6, 2018
Registry last updated
Sep 2, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.