Pancreatic CancerPhase 1NCT01523808
Administration of GRASPA (Suspension of Erythrocytes Encapsulating L-asparaginase)in Patients With Pancreatic Cancer
A Phase 1 study testing GRASPA in people with Pancreatic Cancer, run by ERYtech Pharma.
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… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Pancreatic Cancer
- What is being tested?
- GRASPA
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- No sites listed yet
- Study dates
- Nov 2009to Mar 2011
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
About this study
Official title: Phase I, Dose Escalation Clinical Trial of GRASPA (Red Blood Cells Encapsulating L-Asparaginase) in Patients With Pancreatic Carcinoma
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.
- Conditions
- Pancreatic Cancer
- Being tested
- GRASPA
- Keywords
- pancreatic cancer, asparaginase
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GRASPADrug
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
| Study group | Role | What they receive |
|---|---|---|
| GRASPA 25 | Experimental | Not described Receives: Drug: GRASPA |
| GRASPA 50 | Experimental | Not described Receives: Drug: GRASPA |
| GRASPA 100 | Experimental | Not described Receives: Drug: GRASPA |
| GRASPA 150 | Experimental | Not described Receives: Drug: GRASPA |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 4 weeks
Secondary outcomes (8)
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
Measured: 8 weeks
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.
Measured: Days 0, 1, 3, 7, 14, 21, 28, 35, 42, 56
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.
Measured: Days 0, 1, 3, 7, 14, 21, 28, 35, 42, 56
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.
Measured: Days 0, 1, 3, 7, 14, 21, 28, 35, 42, 56
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.
Measured: Days 0, 1, 3, 7, 14, 21, 28, 35, 42, 56
Number of Patient Positive for Anti-L-asparaginase Antibodies
Titers of E. coli anti-asparaginase antibodies evaluated over time to assess immunogenicity
Measured: Day 0, 1, 28 and 56
Summary of CEA Level Over Time
Assess tumor response, evaluated by carcinoembryonic antigen (CEA) tumor marker evolution
Measured: Day 0, 28, 56
Summary of CA 19.9 Over Time
Tumor response Evaluation by cancer antigen (CA)19.9 evolution over time
Measured: Day 0, 28 and 56
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2012 (estimated)
- Study startNov 2009
- Primary completionMar 2011
- Study completionMar 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pancreatic CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- ERYtech Pharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01523808
- Sponsor's protocol ID
- GRASPANC2008-02
- Status last verified
- Aug 2021
- First submitted
- 16 Jan 2012
- Last updated
- 15 Oct 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 26355551
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I, Dose Escalation Clinical Trial of GRASPA (Red Blood Cells Encapsulating L-Asparaginase) in Patients With Pancreatic Carcinoma
- ClinicalTrials.gov ID
- NCT01523808
- Acronym / sponsor ID
- GRASPANC2008-02
- Conditions
- Pancreatic Cancer
- Keywords
- pancreatic cancer, asparaginase
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- ERYtech PharmaIndustry (pharma, biotech, devices)
- Study start
- Nov 2009
- Primary completion
- Mar 2011 (actual)
- Study completion
- Mar 2011 (actual)
- First posted
- 1 Feb 2012 (estimated)
- Results
- Posted 15 Oct 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| GRASPA 25 | Experimental | Drug: GRASPA |
| GRASPA 50 | Experimental | Drug: GRASPA |
| GRASPA 100 | Experimental | Drug: GRASPA |
| GRASPA 150 | Experimental | Drug: GRASPA |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GRASPAEach 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 | Drug | GRASPA 100, GRASPA 150, GRASPA 25, GRASPA 50 |
Primary outcome
Number of Patients With Dose-limiting Toxicities up to Week 4 After Treatment
Time frame: 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
8 secondary outcomes
Number of Patients With Limiting Toxicities From Week 4 to Week 8 (End of Study)
Time frame: 8 weeks
Encapsulated L-asparaginase Pharmacokinetic Parameters Terminal Half-life
Time frame: Days 0, 1, 3, 7, 14, 21, 28, 35, 42, 56
Encapsulated L-asparaginase Pharmacokinetic Parameters Cmax
Time frame: Days 0, 1, 3, 7, 14, 21, 28, 35, 42, 56
Encapsulated L-asparaginase Pharmacokinetic Parameters Area Under the Curve to Infinity
Time frame: Days 0, 1, 3, 7, 14, 21, 28, 35, 42, 56
Change of Asparagine Levels From Baseline (Pharmacodynamics)
Time frame: Days 0, 1, 3, 7, 14, 21, 28, 35, 42, 56
Number of Patient Positive for Anti-L-asparaginase Antibodies
Time frame: Day 0, 1, 28 and 56
Summary of CEA Level Over Time
Time frame: Day 0, 28, 56
Summary of CA 19.9 Over Time
Time frame: Day 0, 28 and 56
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26355551Bachet 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GRASPA in people with Pancreatic Cancer, run by ERYtech Pharma.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Oct 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Patients With Dose-limiting Toxicities up to Week 4 After Treatment (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01523808, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2021.