Administration of GRASPA (Suspension of Erythrocytes Encapsulating L-asparaginase)in Patients With Pancreatic Cancer
Study Details
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 1 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: GRASPA 25
|
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
|
Experimental: GRASPA 50
|
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
|
Experimental: GRASPA 100
|
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
|
Experimental: GRASPA 150
|
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
|
Outcome Measures
Primary Outcome Measures
- Number of Patients With Dose-limiting Toxicities up to Week 4 After Treatment [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 Outcome Measures
- Number of Patients With Limiting Toxicities From Week 4 to Week 8 (End of Study) [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
- Encapsulated L-asparaginase Pharmacokinetic Parameters Terminal Half-life [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.
- Encapsulated L-asparaginase Pharmacokinetic Parameters Cmax [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.
- Encapsulated L-asparaginase Pharmacokinetic Parameters Area Under the Curve to Infinity [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.
- Change of Asparagine Levels From Baseline (Pharmacodynamics) [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.
- Number of Patient Positive for Anti-L-asparaginase Antibodies [Day 0, 1, 28 and 56]
Titers of E. coli anti-asparaginase antibodies evaluated over time to assess immunogenicity
- Summary of CEA Level Over Time [Day 0, 28, 56]
Assess tumor response, evaluated by carcinoembryonic antigen (CEA) tumor marker evolution
- Summary of CA 19.9 Over Time [Day 0, 28 and 56]
Tumor response Evaluation by cancer antigen (CA)19.9 evolution over time
Eligibility Criteria
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
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- ERYtech Pharma
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- GRASPANC2008-02
Study Results
Participant Flow
Recruitment Details | Participants were recruited at 3 investigational sites in France between November 2009 and February 2011. The first participant was enrolled in the study on 27 November 2009 and the last patient exited the study on 30 March 2011. |
---|---|
Pre-assignment Detail | This was not a randomized study. No washout or run-in was required. Assignment of patients to treatment groups followed study design rules, per protocol. |
Arm/Group Title | GRASPA 25 | GRASPA 50 | GRASPA 100 | GRASPA 150 |
---|---|---|---|---|
Arm/Group Description | 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 | 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 | 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 | 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 |
Period Title: Overall Study | ||||
STARTED | 3 | 3 | 3 | 3 |
COMPLETED | 0 | 3 | 1 | 0 |
NOT COMPLETED | 3 | 0 | 2 | 3 |
Baseline Characteristics
Arm/Group Title | GRASPA 25 | GRASPA 50 | GRASPA 100 | GRASPA 150 | Total |
---|---|---|---|---|---|
Arm/Group Description | Participants received one administration of GRASPA . A stepwise increase of 4 single doses of GRASPA was administered to cohorts of 3 patients per dose 3 subjects enrolled; 0 subjects completed | Each patient will receive one administration of GRASPA . A stepwise increase of 4 single doses of GRASPA was administered to cohorts of 3 patients per dose 3 subjects enrolled; 3 subjects completed | Each patient will receive one administration of GRASPA . A stepwise increase of 4 single doses of GRASPA was administered to cohorts of 3 patients per dose 3 subjects enrolled; 1 subject completed | Each patient will receive one administration of GRASPA . A stepwise increase of 4 single doses of GRASPA was administered to cohorts of 3 patients per dose 3 subjects enrolled; 0 subjects completed | Total of all reporting groups |
Overall Participants | 3 | 3 | 3 | 3 | 12 |
Age (Count of Participants) | |||||
<=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Between 18 and 65 years |
3
100%
|
1
33.3%
|
3
100%
|
1
33.3%
|
8
66.7%
|
>=65 years |
0
0%
|
2
66.7%
|
0
0%
|
2
66.7%
|
4
33.3%
|
Age (years) [Median (Full Range) ] | |||||
Median (Full Range) [years] |
56
|
67
|
51
|
68
|
60
|
Sex: Female, Male (Count of Participants) | |||||
Female |
0
0%
|
1
33.3%
|
1
33.3%
|
1
33.3%
|
3
25%
|
Male |
3
100%
|
2
66.7%
|
2
66.7%
|
2
66.7%
|
9
75%
|
Region of Enrollment (Count of Participants) | |||||
France |
3
100%
|
3
100%
|
3
100%
|
3
100%
|
12
100%
|
Outcome Measures
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 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | GRASPA 25 | GRASPA 50 | GRASPA 100 | GRASPA 150 |
---|---|---|---|---|
Arm/Group Description | 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 3 subjects enrolled; 0 subjects completed | 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 3 subjects enrolled; 3 subjects completed | 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 3 subjects enrolled; 1 subject completed | 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 3 subjects enrolled; 0 subjects completed |
Measure Participants | 3 | 3 | 3 | 3 |
Number [participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
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 |
Outcome Measure Data
Analysis Population Description |
---|
AEs that met the following criteria were considered for the primary safety criterion: Grade 2 to 4 of pancreatic toxicity - no symptomatic pancreatitis occurred for any patients Grade 3 or 4 of hepatic toxicity - Two patients had antithrombin III decrease, but both cases were Grade 1; no cytolytic hepatitis Other grade 4 toxicities |
Arm/Group Title | GRASPA 25 | GRASPA 50 | GRASPA 100 | GRASPA 150 |
---|---|---|---|---|
Arm/Group Description | Participants received one administration of GRASPA . A stepwise increase of 4 single doses of GRASPA was administered to cohorts of 3 patients per dose 3 subjects enrolled; 0 subjects completed | Each patient will receive one administration of GRASPA . A stepwise increase of 4 single doses of GRASPA was administered to cohorts of 3 patients per dose 3 subjects enrolled; 3 subjects completed | Each patient will receive one administration of GRASPA . A stepwise increase of 4 single doses of GRASPA was administered to cohorts of 3 patients per dose 3 subjects enrolled; 1 subject completed | Each patient will receive one administration of GRASPA . A stepwise increase of 4 single doses of GRASPA was administered to cohorts of 3 patients per dose 3 subjects enrolled; 0 subjects completed |
Measure Participants | 3 | 3 | 3 | 3 |
Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
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 |
Outcome Measure Data
Analysis Population Description |
---|
Data were available for dose levels (no. of patients) of 25 IU/kg (n=1), 50 IU/kg (n=0), 100 IU/kg (n=0), and 150 IU/kg (n=3). |
Arm/Group Title | GRASPA 25 | GRASPA 150 |
---|---|---|
Arm/Group Description | 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 3 subjects enrolled; 0 subjects completed | 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 3 subjects enrolled; 0 subjects completed |
Measure Participants | 1 | 3 |
Mean (Standard Deviation) [days] |
19.34
|
22.71
(10.48)
|
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 |
Outcome Measure Data
Analysis Population Description |
---|
Data were available for dose levels (no. of patients) of 25 IU/kg (n=1), 50 IU/kg (n=0), 100 IU/kg (n=0), and 150 IU/kg (n=3). |
Arm/Group Title | GRASPA 25 | GRASPA 150 |
---|---|---|
Arm/Group Description | 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 3 subjects enrolled; 0 subjects completed | 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 3 subjects enrolled; 0 subjects completed |
Measure Participants | 1 | 3 |
Mean (Standard Deviation) [IU/L] |
255.33
|
1812.57
(203.12)
|
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 |
Outcome Measure Data
Analysis Population Description |
---|
Data were available for dose levels (no. of patients) of 25 IU/kg (n=1), 50 IU/kg (n=0), 100 IU/kg (n=0), and 150 IU/kg (n=3). |
Arm/Group Title | GRASPA 25 | GRASPA 150 |
---|---|---|
Arm/Group Description | 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 3 subjects enrolled; 0 subjects completed | 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 3 subjects enrolled; 0 subjects completed |
Measure Participants | 1 | 3 |
Mean (Standard Deviation) [hr*IU/L] |
189363.84
|
1331430.20
(258279.50)
|
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 |
Outcome Measure Data
Analysis Population Description |
---|
12 patients were included and analyzed corresponding to 1 cohort of 3 patients per dose. Data shown is a summary of the relative change of asparagine (%) from baseline over time (analysis set) |
Arm/Group Title | GRASPA 25 | GRASPA 50 | GRASPA 100 | GRASPA 150 |
---|---|---|---|---|
Arm/Group Description | 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 3 subjects enrolled; 0 subjects completed | 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 3 subjects enrolled; 3 subjects completed | 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 3 subjects enrolled; 1 subject completed | 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 3 subjects enrolled; 0 subjects completed |
Measure Participants | 3 | 3 | 3 | 3 |
Day 0 |
0.00
(0.00)
|
0.00
(0.00)
|
0.00
(0.00)
|
0.00
(0.00)
|
Day 1 |
-98.10
(0.35)
|
-98.36
(0.60)
|
-80.22
(31.67)
|
-97.26
(0.02)
|
Day 3 |
-98.10
(0.35)
|
-91.39
(11.49)
|
-72.66
(44.77)
|
-97.36
(0.18)
|
Day 7 |
-37.65
(55.53)
|
-80.06
(15.68)
|
-49.97
(52.19)
|
-93.02
(7.35)
|
Day 14 |
3.74
(33.84)
|
-30.13
(11.06)
|
-6.63
(8.46)
|
-65.91
(54.30)
|
Day 21 |
1.46
(52.13)
|
-13.21
(41.76)
|
-12.93
(9.87)
|
-31.64
(41.65)
|
Day 28 |
8.77
(63.51)
|
-16.24
(40.46)
|
0.94
(2.65)
|
-6.55
(8.54)
|
Day 35 |
-15.61
(33.87)
|
-10.95
(18.03)
|
7.50
|
43.08
|
Day 42 |
-22.04
(47.31)
|
-7.81
|
-1.82
|
|
Day 56 |
-74.80
|
-7.26
|
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 |
Outcome Measure Data
Analysis Population Description |
---|
Summary of anti-L-asparaginase antibodies over time by number of patients |
Arm/Group Title | GRASPA 25 | GRASPA 50 | GRASPA 100 | GRASPA 150 |
---|---|---|---|---|
Arm/Group Description | 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 3 subjects enrolled; 0 subjects completed | 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 3 subjects enrolled; 3 subjects completed | 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 3 subjects enrolled; 1 subject completed | 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 3 subjects enrolled; 0 subjects completed |
Measure Participants | 3 | 3 | 3 | 3 |
Day 0 |
0
0%
|
0
0%
|
1
33.3%
|
0
0%
|
Day 1 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Day 28 |
2
66.7%
|
3
100%
|
3
100%
|
0
0%
|
Day 56 |
2
66.7%
|
1
33.3%
|
2
66.7%
|
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 |
Outcome Measure Data
Analysis Population Description |
---|
Sample collection not completed at each timepoint for each patient. All data available presented below. |
Arm/Group Title | GRASPA 25 | GRASPA 50 | GRASPA 100 | GRASPA 150 |
---|---|---|---|---|
Arm/Group Description | 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 | 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 | 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 | 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 |
Measure Participants | 3 | 3 | 3 | 3 |
Day 0 |
21.3
|
10.2
|
6.4
|
354.8
|
Day 28 |
22.8
|
26.3
|
3.1
|
967.9
|
Day 56 |
9.0
|
3.4
|
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 |
Outcome Measure Data
Analysis Population Description |
---|
Sample collection not completed at each timepoint for each patient. All data available presented below. |
Arm/Group Title | GRASPA 25 | GRASPA 50 | GRASPA 100 | GRASPA 150 |
---|---|---|---|---|
Arm/Group Description | 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 3 subjects enrolled; 0 subjects completed | 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 3 subjects enrolled; 3 subjects completed | 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 3 subjects enrolled; 1 subject completed | 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 3 subjects enrolled; 0 subjects completed |
Measure Participants | 3 | 3 | 3 | 3 |
Day 0 |
18440.0
|
184.3
|
1625.0
|
54.5
|
Day 28 |
37196.5
|
748.3
|
3136.0
|
124.1
|
Day 56 |
561.8
|
195.5
|
Adverse Events
Time Frame | Reported Adverse Events (AEs) include events starting from patient inclusion until 2 month after GRASPA administration (~2.5 months) | |||||||
---|---|---|---|---|---|---|---|---|
Adverse Event Reporting Description | Adverse events regardless of grade or causality are reported. Events are summarized by system organ class and footnote indicates the specific events reported for each class. | |||||||
Arm/Group Title | GRASPA 25 | GRASPA 50 | GRASPA 100 | GRASPA 150 | ||||
Arm/Group Description | 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 3 subjects enrolled; 0 subjects completed | 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 3 subjects enrolled; 3 subjects completed | 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 3 subjects enrolled; 1 subject completed | 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 3 subjects enrolled; 0 subjects completed | ||||
All Cause Mortality |
||||||||
GRASPA 25 | GRASPA 50 | GRASPA 100 | GRASPA 150 | |||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 1/3 (33.3%) | 0/3 (0%) | 1/3 (33.3%) | 1/3 (33.3%) | ||||
Serious Adverse Events |
||||||||
GRASPA 25 | GRASPA 50 | GRASPA 100 | GRASPA 150 | |||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 3/3 (100%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | ||||
Gastrointestinal disorders | ||||||||
Increase of Abdominal Pain | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | ||||
Musculoskeletal and connective tissue disorders | ||||||||
Increase of Lumbar Pain | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | ||||
Respiratory, thoracic and mediastinal disorders | ||||||||
Dyspnea related to pleural effusion | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
GRASPA 25 | GRASPA 50 | GRASPA 100 | GRASPA 150 | |||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 3/3 (100%) | 3/3 (100%) | 2/3 (66.7%) | 2/3 (66.7%) | ||||
Gastrointestinal disorders | ||||||||
Abdominal Pain | 3/3 (100%) | 3 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 |
Ascites | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
Constipation | 2/3 (66.7%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/3 (66.7%) | 2 |
Nausea | 2/3 (66.7%) | 2 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 2/3 (66.7%) | 2 |
Diarrohea | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 |
Vomiting | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 |
Gastroesophageal reflux | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 |
Tongue disorder | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 |
Stomatitis | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 |
General disorders | ||||||||
Astenia | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 |
Fatigue | 0/3 (0%) | 0 | 1/3 (33.3%) | 2 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 |
Oedema peripheral | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 |
Pyrexia | 2/3 (66.7%) | 2 | 1/3 (33.3%) | 3 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 |
Investigations | ||||||||
ECOG Performance Status worsened | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
Antithrombin III decreased | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 |
Weight decreased | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 |
Metabolism and nutrition disorders | ||||||||
Decreased appetite | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 |
Gout | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
Hyperglycaemia | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
Musculoskeletal and connective tissue disorders | ||||||||
Back pain | 1/3 (33.3%) | 2 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 |
Muscle spasm | 0/3 (0%) | 0 | 2/3 (66.7%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
Musculoskeletal pain | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Director of Clinical Trials |
---|---|
Organization | Erytech Pharmaceuticals |
Phone | +33 4 78 74 44 38 |
contact@erytech.com |
- GRASPANC2008-02