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Administration of GRASPA (Suspension of Erythrocytes Encapsulating L-asparaginase)in Patients With Pancreatic Cancer

Primary Purpose

Pancreatic Cancer

Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
GRASPA
Sponsored by
ERYtech Pharma
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pancreatic Cancer focused on measuring pancreatic cancer, asparaginase

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Exocrine pancreatic adenocarcinoma cytologically or histologically confirmed
  • Locally advanced and non-resectable with invasion of the superior mesenteric artery (stage III) or metastatic (stage IV) as defined by TNM (primary tumor, regional nodes, metastasis) 2002 classification (UICC 2002)
  • resistant to a first or second line chemotherapy with gemcitabine
  • Patient aged between 18 to 70 years
  • Signed Informed Consent Form
  • Life expectancy ≥ 12 weeks
  • Accurate measurement of tumor volume by imagery (in at least one dimension)
  • Presence of one or several tumor markers (carcinoembryonic antigen [CEA] and cancer antigen [CA] 19.9)
  • Eastern Cooperative Oncology Group [ECOG] Prognostic Score : 0, 1 or 2
  • Patient beneficiary of a Social Security Insurance

Exclusion Criteria:

  • Patient with an endocrine or acinar pancreatic tumor
  • Patient with known or suspected cerebro-meningeal metastases
  • Haemoglobin level greater than 13 g/L
  • Patient hypersensitive to L-asparaginase or have had prior exposure to any form of L-asparaginase
  • Splenic vein thrombosis < 3 months or under active treatment
  • Anti-vitamin K treatment
  • Hepatic Insufficiency unrelated to pancreatic cancer
  • Renal insufficiency unrelated to pancreatic cancer
  • Pancreatitis or pancreatitis history unrelated to pancreatic cancer
  • Insulin-dependant diabetes mellitus unrelated to pancreatic cancer
  • Current or prior coagulopathy disorders unrelated to pancreatic cancer
  • ECOG Prognostic Score 3 or 4
  • History of grade 3 blood transfusion reaction (life threatening situation)
  • Presence of rare and dangerous anti-erythrocyte antibodies preventing from getting a compatible packed Red Blood Cells for the patient
  • Patient already included in another clinical trial
  • Pregnancy, breast-feeding or absence of secured contraception
  • Unwillingness to sign the informed consent form

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm Type

    Experimental

    Experimental

    Experimental

    Experimental

    Arm Label

    GRASPA 25

    GRASPA 50

    GRASPA 100

    GRASPA 150

    Arm Description

    Outcomes

    Primary Outcome Measures

    Number of Patients With Dose-limiting Toxicities up to Week 4 After Treatment
    Dose limiting toxicities were defined according to CTCAE v3.0 as follow: Known toxicities related to asparaginase: Pancreatic grade 2, 3 or 4 Allergic, Neurological, Hepatic, Coagulation grade 3 or 4 an any other toxicity of grade 4

    Secondary Outcome Measures

    Number of Patients With Limiting Toxicities From Week 4 to Week 8 (End of Study)
    Limiting toxicities were defined according to CTCAE v3.0 as follow: Known toxicities related to asparaginase: Pancreatic grade 2, 3 or 4 Allergic, Neurological, Hepatic, Coagulation grade 3 or 4 Any other toxicity of grade 4
    Encapsulated L-asparaginase Pharmacokinetic Parameters Terminal Half-life
    Pharmacokinetic (PK) parameters were analyzed for encapsulated asparaginase concentration data using Phoenix® WinNonlin® 6.3. Free and total L-asparaginase activity was measured during the study and encapsulated asparaginase was defined as the difference between total asparaginase and plasmatic asparaginase.
    Encapsulated L-asparaginase Pharmacokinetic Parameters Cmax
    Pharmacokinetic (PK) parameters were analyzed for encapsulated asparaginase concentration data using Phoenix® WinNonlin® 6.3. Free and total L-asparaginase activity was measured during the study and encapsulated asparaginase was defined as the difference between total asparaginase and plasmatic asparaginase.
    Encapsulated L-asparaginase Pharmacokinetic Parameters Area Under the Curve to Infinity
    Pharmacokinetic (PK) parameters were analyzed for encapsulated asparaginase concentration data using Phoenix® WinNonlin® 6.3. Free and total L-asparaginase activity was measured during the study and encapsulated asparaginase was defined as the difference between total asparaginase and plasmatic asparaginase.
    Change of Asparagine Levels From Baseline (Pharmacodynamics)
    Duration of plasma asparagine depletion (less than or equal to 2 micromoles/Liter or deamination greater than 90% compared to baseline levels and serum concentrations of L-asparagine, L-aspartate, L-glutamine, and L-glutamate. For pharmacodynamic data, the administration date of the investigational treatment was considered as the reference date for duration calculation. All patients having received a single dose of studied drug GRASPA have been analyzed.
    Number of Patient Positive for Anti-L-asparaginase Antibodies
    Titers of E. coli anti-asparaginase antibodies evaluated over time to assess immunogenicity
    Summary of CEA Level Over Time
    Assess tumor response, evaluated by carcinoembryonic antigen (CEA) tumor marker evolution
    Summary of CA 19.9 Over Time
    Tumor response Evaluation by cancer antigen (CA)19.9 evolution over time

    Full Information

    First Posted
    January 16, 2012
    Last Updated
    September 20, 2021
    Sponsor
    ERYtech Pharma
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01523808
    Brief Title
    Administration of GRASPA (Suspension of Erythrocytes Encapsulating L-asparaginase)in Patients With Pancreatic Cancer
    Official Title
    Phase I, Dose Escalation Clinical Trial of GRASPA (Red Blood Cells Encapsulating L-Asparaginase) in Patients With Pancreatic Carcinoma
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2021
    Overall Recruitment Status
    Completed
    Study Start Date
    November 2009 (undefined)
    Primary Completion Date
    March 2011 (Actual)
    Study Completion Date
    March 2011 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    ERYtech Pharma

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    The interest in using L-asparaginase in pancreatic cancer arose from in vitro and in vivo studies data showing an anti-neoplastic effect on pancreatic tumor cell lines. Interestingly, these studies suggest an additional effect of L-asparaginase associated to gemcitabine.GRASPA is a suspension of red blood cells encapsulating L-asparaginase. The aim of this phase I clinical trial is to evaluate the Maximum Tolerated Dose (MTD) of GRASPA on locally advanced or metastatic pancreatic tumors, after therapy failure of first or second line chemotherapy using gemcitabine.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Pancreatic Cancer
    Keywords
    pancreatic cancer, asparaginase

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    12 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    GRASPA 25
    Arm Type
    Experimental
    Arm Title
    GRASPA 50
    Arm Type
    Experimental
    Arm Title
    GRASPA 100
    Arm Type
    Experimental
    Arm Title
    GRASPA 150
    Arm Type
    Experimental
    Intervention Type
    Drug
    Intervention Name(s)
    GRASPA
    Intervention Description
    Each patient will receive one administration of GRASPA . A stepwise increase of 4 single doses of GRASPA will be administered to cohorts of 3 patients per dose
    Primary Outcome Measure Information:
    Title
    Number of Patients With Dose-limiting Toxicities up to Week 4 After Treatment
    Description
    Dose limiting toxicities were defined according to CTCAE v3.0 as follow: Known toxicities related to asparaginase: Pancreatic grade 2, 3 or 4 Allergic, Neurological, Hepatic, Coagulation grade 3 or 4 an any other toxicity of grade 4
    Time Frame
    4 weeks
    Secondary Outcome Measure Information:
    Title
    Number of Patients With Limiting Toxicities From Week 4 to Week 8 (End of Study)
    Description
    Limiting toxicities were defined according to CTCAE v3.0 as follow: Known toxicities related to asparaginase: Pancreatic grade 2, 3 or 4 Allergic, Neurological, Hepatic, Coagulation grade 3 or 4 Any other toxicity of grade 4
    Time Frame
    8 weeks
    Title
    Encapsulated L-asparaginase Pharmacokinetic Parameters Terminal Half-life
    Description
    Pharmacokinetic (PK) parameters were analyzed for encapsulated asparaginase concentration data using Phoenix® WinNonlin® 6.3. Free and total L-asparaginase activity was measured during the study and encapsulated asparaginase was defined as the difference between total asparaginase and plasmatic asparaginase.
    Time Frame
    Days 0, 1, 3, 7, 14, 21, 28, 35, 42, 56
    Title
    Encapsulated L-asparaginase Pharmacokinetic Parameters Cmax
    Description
    Pharmacokinetic (PK) parameters were analyzed for encapsulated asparaginase concentration data using Phoenix® WinNonlin® 6.3. Free and total L-asparaginase activity was measured during the study and encapsulated asparaginase was defined as the difference between total asparaginase and plasmatic asparaginase.
    Time Frame
    Days 0, 1, 3, 7, 14, 21, 28, 35, 42, 56
    Title
    Encapsulated L-asparaginase Pharmacokinetic Parameters Area Under the Curve to Infinity
    Description
    Pharmacokinetic (PK) parameters were analyzed for encapsulated asparaginase concentration data using Phoenix® WinNonlin® 6.3. Free and total L-asparaginase activity was measured during the study and encapsulated asparaginase was defined as the difference between total asparaginase and plasmatic asparaginase.
    Time Frame
    Days 0, 1, 3, 7, 14, 21, 28, 35, 42, 56
    Title
    Change of Asparagine Levels From Baseline (Pharmacodynamics)
    Description
    Duration of plasma asparagine depletion (less than or equal to 2 micromoles/Liter or deamination greater than 90% compared to baseline levels and serum concentrations of L-asparagine, L-aspartate, L-glutamine, and L-glutamate. For pharmacodynamic data, the administration date of the investigational treatment was considered as the reference date for duration calculation. All patients having received a single dose of studied drug GRASPA have been analyzed.
    Time Frame
    Days 0, 1, 3, 7, 14, 21, 28, 35, 42, 56
    Title
    Number of Patient Positive for Anti-L-asparaginase Antibodies
    Description
    Titers of E. coli anti-asparaginase antibodies evaluated over time to assess immunogenicity
    Time Frame
    Day 0, 1, 28 and 56
    Title
    Summary of CEA Level Over Time
    Description
    Assess tumor response, evaluated by carcinoembryonic antigen (CEA) tumor marker evolution
    Time Frame
    Day 0, 28, 56
    Title
    Summary of CA 19.9 Over Time
    Description
    Tumor response Evaluation by cancer antigen (CA)19.9 evolution over time
    Time Frame
    Day 0, 28 and 56

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    70 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Exocrine pancreatic adenocarcinoma cytologically or histologically confirmed Locally advanced and non-resectable with invasion of the superior mesenteric artery (stage III) or metastatic (stage IV) as defined by TNM (primary tumor, regional nodes, metastasis) 2002 classification (UICC 2002) resistant to a first or second line chemotherapy with gemcitabine Patient aged between 18 to 70 years Signed Informed Consent Form Life expectancy ≥ 12 weeks Accurate measurement of tumor volume by imagery (in at least one dimension) Presence of one or several tumor markers (carcinoembryonic antigen [CEA] and cancer antigen [CA] 19.9) Eastern Cooperative Oncology Group [ECOG] Prognostic Score : 0, 1 or 2 Patient beneficiary of a Social Security Insurance Exclusion Criteria: Patient with an endocrine or acinar pancreatic tumor Patient with known or suspected cerebro-meningeal metastases Haemoglobin level greater than 13 g/L Patient hypersensitive to L-asparaginase or have had prior exposure to any form of L-asparaginase Splenic vein thrombosis < 3 months or under active treatment Anti-vitamin K treatment Hepatic Insufficiency unrelated to pancreatic cancer Renal insufficiency unrelated to pancreatic cancer Pancreatitis or pancreatitis history unrelated to pancreatic cancer Insulin-dependant diabetes mellitus unrelated to pancreatic cancer Current or prior coagulopathy disorders unrelated to pancreatic cancer ECOG Prognostic Score 3 or 4 History of grade 3 blood transfusion reaction (life threatening situation) Presence of rare and dangerous anti-erythrocyte antibodies preventing from getting a compatible packed Red Blood Cells for the patient Patient already included in another clinical trial Pregnancy, breast-feeding or absence of secured contraception Unwillingness to sign the informed consent form

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    26355551
    Citation
    Bachet JB, Gay F, Marechal R, Galais MP, Adenis A, MsC DS, Cros J, Demetter P, Svrcek M, Bardier-Dupas A, Emile JF, Hammel P, Ebenezer C, Berlier W, Godfrin Y, Andre T. Asparagine Synthetase Expression and Phase I Study With L-Asparaginase Encapsulated in Red Blood Cells in Patients With Pancreatic Adenocarcinoma. Pancreas. 2015 Oct;44(7):1141-7. doi: 10.1097/MPA.0000000000000394.
    Results Reference
    derived

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    Administration of GRASPA (Suspension of Erythrocytes Encapsulating L-asparaginase)in Patients With Pancreatic Cancer

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