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

NCT01523808 | Completed Phase 1 Results DMC

• 1 other identifier: GRASPANC2008-02
• Study Type: interventional
• Target: 12
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Pancreatic Cancer

Keywords

pancreatic cancer; asparaginase

Outcome Measures

Primary Outcomes (1)

• 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

  4 weeks

Secondary Outcomes (8)

• Number of Patients With Limiting Toxicities From Week 4 to Week 8 (End of Study)

  8 weeks

• Encapsulated L-asparaginase Pharmacokinetic Parameters Terminal Half-life

  Days 0, 1, 3, 7, 14, 21, 28, 35, 42, 56

• Encapsulated L-asparaginase Pharmacokinetic Parameters Cmax

  Days 0, 1, 3, 7, 14, 21, 28, 35, 42, 56

• Encapsulated L-asparaginase Pharmacokinetic Parameters Area Under the Curve to Infinity

  Days 0, 1, 3, 7, 14, 21, 28, 35, 42, 56

• Change of Asparagine Levels From Baseline (Pharmacodynamics)

  Days 0, 1, 3, 7, 14, 21, 28, 35, 42, 56

Study Arms (4)

GRASPA 25

EXPERIMENTAL

Drug: GRASPA

GRASPA 50

EXPERIMENTAL

Drug: GRASPA

GRASPA 100

EXPERIMENTAL

Drug: GRASPA

GRASPA 150

EXPERIMENTAL

Drug: GRASPA

Interventions

GRASPA DRUG

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 100; GRASPA 150; GRASPA 25; GRASPA 50

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• ERYtech Pharma: lead

Related Publications (1)

• 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.

  PMID: 26355551 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Director of Clinical Trials
• Organization: Erytech Pharmaceuticals

contact@erytech.com

+33 4 78 74 44 38

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 16, 2012
• First Posted: February 1, 2012
• Study Start: November 1, 2009
• Primary Completion: March 1, 2011
• Study Completion: March 1, 2011
• Last Updated: October 15, 2021
• Results First Posted: October 15, 2021

Record last verified: 2021-08