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

Sponsor
University of Birmingham (Other)
Overall Status
Unknown status
CT.gov ID
NCT03455140
Collaborator
(none)
64
Enrollment
8
Locations
4
Arms
31.1
Anticipated Duration (Months)
8
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: PEG- BCT-100
 Phase 1/Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
64 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Aug 28, 2018
Anticipated Primary Completion Date :
Apr 1, 2021
Anticipated Study Completion Date :
Apr 1, 2021

Arms and Interventions

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

    		•

    Outcome Measures

    Primary Outcome Measures

    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 [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. [After 8 weeks]

      Disease response (Complete Response (CR) or Partial Response (PR)) after 8 weeks of treatment with BCT-100

    Secondary Outcome Measures

    1. The incidence and severity of Adverse Events (AEs) as Assessed by CTCAE v4 [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 [Within 1 year]

      Disease response ( CR / PR) according to Cheson criteria

    3. Disease response - Sarcoma [Within 1 year]

      Disease response ( CR / PR) according to RECIST criteria

    4. Disease response - High Grade Glioma [Within 1 year]

      Disease response ( CR / PR) according to RANO criteria

    5. Disease response - Neuroblastoma [Within 1 year]

      Disease response ( CR / PR) according to INCR criteria

    6. Progression free survival (PFS) [Up to three years after registration]

    7. Overall survival (OS). [Up to three years after registration]

    8. Maximum Plasma Concentration [Cmax], of BCT-100 in the paediatric population. [Up to 24 weeks]

    9. Time to maximum Plasma Concentration [Tmax], of BCT-100 in the paediatric population. [Up to 24 weeks]

    10. Minimum Plasma Concentration [Cmin], of BCT-100 in the paediatric population. [Up to 24 weeks]

    11. Area Under the Curve [AUC], of BCT-100 in the paediatric population. [Up to 24 weeks]

    12. Duration of adequate arginine depletion in blood. [Up to 24 weeks]

      BCT-100 concentration in blood

    13. Duration of adequate arginine depletion in bone marrow . [Up to 24 weeks]

      BCT-100 concentration in bone marrow

    14. Duration of adequate arginine depletion in cerebrospinal fluid. [Up to 24 weeks]

      BCT-100 concentration in cerebrospinal fluid

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    1 Year to 25 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Women's & Children's Hospital Adelaide Australia
    2 Birmingham Children's Hospital Birmingham United Kingdom
    3 Bristol Royal Hospital for Children Bristol United Kingdom
    4 Addenbrookes Hospital Cambridge United Kingdom
    5 Royal Hospital for Children Glasgow United Kingdom
    6 Leeds Children's Hospital Leeds United Kingdom
    7 Royal Manchester Children's Hospital Manchester United Kingdom
    8 Royal Marsden Hospital Sutton United Kingdom

    Sponsors and Collaborators

    • University of Birmingham

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    University of Birmingham
    ClinicalTrials.gov Identifier:
    NCT03455140
    Other Study ID Numbers:
    • RG_16-040
    First Posted:
    Mar 6, 2018
    Last Update Posted:
    Mar 25, 2020
    Last Verified:
    Mar 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by University of Birmingham
    Arginine
    Arginase
    Children
    Young Adult
    Additional relevant MeSH terms:
    BCT-100

    Study Results

    No Results Posted as of Mar 25, 2020