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

Sponsor
ERYtech Pharma (Industry)
Overall Status
Completed
CT.gov ID
NCT01523808
Collaborator
(none)
12
4
15.9

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

Study Type:
Interventional
Actual Enrollment :
12 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase I, Dose Escalation Clinical Trial of GRASPA (Red Blood Cells Encapsulating L-Asparaginase) in Patients With Pancreatic Carcinoma
Study Start Date :
Nov 1, 2009
Actual Primary Completion Date :
Mar 1, 2011
Actual Study Completion Date :
Mar 1, 2011

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

  1. 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

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. Summary of CEA Level Over Time [Day 0, 28, 56]

    Assess tumor response, evaluated by carcinoembryonic antigen (CEA) tumor marker evolution

  8. 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

Ages Eligible for Study:
18 Years to 70 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.
Responsible Party:
ERYtech Pharma
ClinicalTrials.gov Identifier:
NCT01523808
Other Study ID Numbers:
  • GRASPANC2008-02
First Posted:
Feb 1, 2012
Last Update Posted:
Oct 15, 2021
Last Verified:
Aug 1, 2021
Keywords provided by ERYtech Pharma
Additional relevant MeSH terms:

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

1. Primary Outcome
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%
2. Secondary Outcome
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%
3. Secondary Outcome
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)
4. Secondary Outcome
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)
5. Secondary Outcome
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)
6. Secondary Outcome
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
7. Secondary Outcome
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%
8. Secondary Outcome
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
9. Secondary Outcome
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

[Not Specified]

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
Email contact@erytech.com
Responsible Party:
ERYtech Pharma
ClinicalTrials.gov Identifier:
NCT01523808
Other Study ID Numbers:
  • GRASPANC2008-02
First Posted:
Feb 1, 2012
Last Update Posted:
Oct 15, 2021
Last Verified:
Aug 1, 2021