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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03455140
Recruitment Status : Recruiting
First Posted : March 6, 2018
Last Update Posted : March 25, 2020
Sponsor:
Information provided by (Responsible Party):
University of Birmingham

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
Cancer Pediatric Solid Tumor Pediatric AML Pediatric ALL Drug: PEG- BCT-100 Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : August 28, 2018
Estimated Primary Completion Date : April 2021
Estimated Study Completion Date : April 2021


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 Name: 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 Name: 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 Name: 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 Name: rhArg1peg5000




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 [ 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 Outcome Measures :
  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



Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year to 25 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03455140


Contacts
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Contact: Nicola Fenwick, BMedSc +44 121 415 8782 n.fenwick@bham.ac.uk

Locations
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Australia
Women's & Children's Hospital Recruiting
Adelaide, Australia
Contact: Dr Kirby         
United Kingdom
Birmingham Children's Hospital Recruiting
Birmingham, United Kingdom
Contact: Dr Mussai         
Bristol Royal Hospital for Children Recruiting
Bristol, United Kingdom
Contact: Dr Ng         
Addenbrookes Hospital Recruiting
Cambridge, United Kingdom
Contact: Dr Burke         
Royal Hospital for Children Not yet recruiting
Glasgow, United Kingdom
Contact: Dr McIntosh         
Leeds Children's Hospital Recruiting
Leeds, United Kingdom
Contact: Dr Elliott         
Royal Manchester Children's Hospital Recruiting
Manchester, United Kingdom
Contact: Dr Makin         
Royal Marsden Hospital Recruiting
Sutton, United Kingdom
Contact: Dr Lancaster         
Sponsors and Collaborators
University of Birmingham
Investigators
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Study Chair: Francis J Mussai, DPhil University of Birmingham
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Responsible Party: University of Birmingham
ClinicalTrials.gov Identifier: NCT03455140    
Other Study ID Numbers: RG_16-040
First Posted: March 6, 2018    Key Record Dates
Last Update Posted: March 25, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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:
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BCT-100
Antineoplastic Agents