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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
ERYtech Pharma
ClinicalTrials.gov Identifier:
NCT01523808
First received: January 16, 2012
Last updated: March 7, 2013
Last verified: March 2013
  Purpose

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 Intervention Phase
Pancreatic Cancer
Drug: GRASPA
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by ERYtech Pharma:

Primary Outcome Measures:
  • limiting toxicity [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]

    Toxicity(ies) considered as dose limiting, defined according to the "Common Terminology Criteria for Adverse Events v3.0" (CTCAE v3.0) scale toxicities are :

    • grade 2,3 or 4 for pancreatic toxicities,
    • grade 3 or 4 for allergies (hypersensitivity), neurological, hepatic and /or coagulation toxicities
    • all other grade 4 toxicity


Secondary Outcome Measures:
  • Immunogenicity : Titers of anti-L-asparaginase antibodies [ Time Frame: 0,1,28,56 days post-dose ] [ Designated as safety issue: No ]
  • Tumor response Evaluation by one or several tumor (bio)markers evolution [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Serum concentrations of asparagine, aspartate, glutamine, glutamate, and asparaginase [ Time Frame: 0,1,3,7,14,21,28,35,42,56 days post-dose ] [ Designated as safety issue: No ]

Enrollment: 12
Study Start Date: June 2009
Study Completion Date: March 2011
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 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 (CEA and CA 19.9)
  • 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: ERYtech Pharma
ClinicalTrials.gov Identifier: NCT01523808     History of Changes
Other Study ID Numbers: GRASPANC2008-02
Study First Received: January 16, 2012
Last Updated: March 7, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by ERYtech Pharma:
pancreatic cancer
asparaginase

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Asparaginase
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 26, 2014