Clinical trial NCT01523808: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pancreatic Cancer
Keywords: pancreatic cancer
asparaginase
Lead sponsor: ERYtech Pharma
Sponsor class: INDUSTRY
First posted: 2012-02-01
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Number of Patients With Dose-limiting Toxicities up to Week 4 After Treatment
timeFrame: 4 weeks
Secondary outcomes:
measure: Number of Patients With Limiting Toxicities From Week 4 to Week 8 (End of Study)
timeFrame: 8 weeks
measure: Encapsulated L-asparaginase Pharmacokinetic Parameters Terminal Half-life
timeFrame: Days 0, 1, 3, 7, 14, 21, 28, 35, 42, 56
measure: Encapsulated L-asparaginase Pharmacokinetic Parameters Cmax
timeFrame: Days 0, 1, 3, 7, 14, 21, 28, 35, 42, 56
measure: Encapsulated L-asparaginase Pharmacokinetic Parameters Area Under the Curve to Infinity
timeFrame: Days 0, 1, 3, 7, 14, 21, 28, 35, 42, 56
measure: Change of Asparagine Levels From Baseline (Pharmacodynamics)
timeFrame: Days 0, 1, 3, 7, 14, 21, 28, 35, 42, 56
measure: Number of Patient Positive for Anti-L-asparaginase Antibodies
timeFrame: Day 0, 1, 28 and 56
measure: Summary of CEA Level Over Time
timeFrame: Day 0, 28, 56
measure: Summary of CA 19.9 Over Time
timeFrame: Day 0, 28 and 56
Other outcomes:
Locations:
Study officials:
References:
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.