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
About this trial
This is an interventional treatment trial for Pancreatic Cancer focused on measuring pancreatic cancer, asparaginase
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
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
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
Learn more about this trial
Administration of GRASPA (Suspension of Erythrocytes Encapsulating L-asparaginase)in Patients With Pancreatic Cancer
We'll reach out to this number within 24 hrs