Administration of GRASPA (Suspension of Erythrocytes Encapsulating L-asparaginase)in Patients With Pancreatic Cancer
Condition: Pancreatic Cancer
MeSH terms: Pancreatic Neoplasms
Intervention: 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
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: pancreatic cancer; asparaginase

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.
    

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