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

Pancreatic Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01523808
• Other study ID #: GRASPANC2008-02
• Status: Completed
• Phase: Phase 1
• Start date: November 2009
• Est. completion date: March 2011

Study information

• Verified date: August 2021
• Source: ERYtech Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: March 2011
• Est. primary completion date: March 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Drug:
• GRASPA
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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
ERYtech Pharma

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	4 weeks
Secondary	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	8 weeks
Secondary	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.	Days 0, 1, 3, 7, 14, 21, 28, 35, 42, 56
Secondary	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.	Days 0, 1, 3, 7, 14, 21, 28, 35, 42, 56
Secondary	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.	Days 0, 1, 3, 7, 14, 21, 28, 35, 42, 56
Secondary	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.	Days 0, 1, 3, 7, 14, 21, 28, 35, 42, 56
Secondary	Number of Patient Positive for Anti-L-asparaginase Antibodies	Titers of E. coli anti-asparaginase antibodies evaluated over time to assess immunogenicity	Day 0, 1, 28 and 56
Secondary	Summary of CEA Level Over Time	Assess tumor response, evaluated by carcinoembryonic antigen (CEA) tumor marker evolution	Day 0, 28, 56
Secondary	Summary of CA 19.9 Over Time	Tumor response Evaluation by cancer antigen (CA)19.9 evolution over time	Day 0, 28 and 56