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NCT Number: NCT01523808

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

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.

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Key information

Conditions

Pancreatic Cancer Digestive System Diseases Digestive System Neoplasms Endocrine Gland Neoplasms Endocrine System Diseases Neoplasms Neoplasms by Site Pancreatic Diseases Pancreatic Neoplasms

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Who can participate

Healthy volunteers accepted: No

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

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

Treatment and study plan

GRASPA

Drug

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 outcomes

  1. Number of Patients With Dose-limiting Toxicities up to Week 4 After Treatment

    Time frame: 4 weeks

    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 outcomes

  1. Number of Patients With Limiting Toxicities From Week 4 to Week 8 (End of Study)

    Time frame: 8 weeks

    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

  2. Encapsulated L-asparaginase Pharmacokinetic Parameters Terminal Half-life

    Time frame: Days 0, 1, 3, 7, 14, 21, 28, 35, 42, 56

    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.

  3. Encapsulated L-asparaginase Pharmacokinetic Parameters Cmax

    Time frame: Days 0, 1, 3, 7, 14, 21, 28, 35, 42, 56

    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.

  4. Encapsulated L-asparaginase Pharmacokinetic Parameters Area Under the Curve to Infinity

    Time frame: Days 0, 1, 3, 7, 14, 21, 28, 35, 42, 56

    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.

  5. Change of Asparagine Levels From Baseline (Pharmacodynamics)

    Time frame: Days 0, 1, 3, 7, 14, 21, 28, 35, 42, 56

    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.

  6. Number of Patient Positive for Anti-L-asparaginase Antibodies

    Time frame: Day 0, 1, 28 and 56

    Titers of E. coli anti-asparaginase antibodies evaluated over time to assess immunogenicity

  7. Summary of CEA Level Over Time

    Time frame: Day 0, 28, 56

    Assess tumor response, evaluated by carcinoembryonic antigen (CEA) tumor marker evolution

  8. Summary of CA 19.9 Over Time

    Time frame: Day 0, 28 and 56

    Tumor response Evaluation by cancer antigen (CA)19.9 evolution over time

Sponsors and collaborators

Lead sponsor

ERYtech Pharma

Industry

Registry information

Official study title

Phase I, Dose Escalation Clinical Trial of GRASPA (Red Blood Cells Encapsulating L-Asparaginase) in Patients With Pancreatic Carcinoma

Important dates

Study start
2009
Primary completion
2011
Study completion
2011
First posted
Feb 1, 2012
Registry last updated
Oct 15, 2021

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.

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