Efficacy and Safety of L-asparaginase Encapsulated in RBC Combined With Gemcitabine or FOLFOX in 2nd Line for Progressive Metastatic Pancreatic Carcinoma

NCT02195180 | Completed Phase 2 DMC

• 2 other identifiers: GRASPANC 2013-032013-004262-34
• Study Type: interventional
• Target: 141
• Locations: 1 country
• Sites: 16

Brief Summary

A new approach that aims to destroy pancreatic tumor cells through modification of the tumor environment. Asparagine synthetase (ASNS) is an enzyme wich synthetise asparagine. Asparagine is an essential nutriment for pancreatic cancer cells which have no or low level of ASNS. by L-asparaginase encapsulated in erythrocytes deplete (supress) Plasma asparagine. in selected patients having no or low ASNS, may provide a new therapeutic approach.

Conditions

Pancreatic Adenocarcinoma Metastatic

Keywords

Pancreas; adenocarcinoma; cancer; asparaginase; erythrocytes; red blood cell; Encapsulation; folfox; gemcitabine

Outcome Measures

Primary Outcomes (2)

• Overall survival (OS)

  Evaluate the effects of eryaspase when combined with chemotherapy for the second line treatment of patients with pancreatic adenocarcinoma in terms of OS, whose tumors has low or no ASNS expression (ASNS 0 or 1+)

  From last study treatment assessment visit until patient's death, loss to follow up, or study closure, assessed up to 36 months.

• Progression free survival (PFS)

  Evaluate the effects of eryaspase when combined with chemotherapy for the second line treatment of patients with pancreatic adenocarcinoma in terms of PFS, whose tumors has low or no ASNS expression (ASNS 0 or 1+)

  From date of randomization to first documented progression of disease, death for any cause or until start of new anti-cancer treatment, whcihever came first, assessed up to 24 months.

Secondary Outcomes (9)

• Incidence of Treatment Emergent Adverse Events (Safety and Tolerability)

  collected from time of informed consent until 4 weeks after last study treatment

• Overall survival

  From last study treatment assessment visit until patient's death, loss to follow up, or study closure, assessed up to 36 months.

• Progression free survival

  From date of randomization to first documented progression of disease, death for any cause or until start of new anti-cancer treatment, whcihever came first, assessed up to 24 months.

• Objective response rate (ORR)

  From date of randomization to last tumor assessment data collected for each patient, assessed up to 24 months.

• Disease control rate (DCR)

  From date of randomization to 16 and 24 weeks.

Study Arms (2)

standard of care combined with ERY001

EXPERIMENTAL

standard of care = Gemcitabine or folfox

Drug: ERY001; Drug: Gemcitabine; Drug: 5-fluoro-uracil/oxaliplatin/leucovorin (folfox)

standard of care alone

SHAM COMPARATOR

standard of care = Gemcitabine or folfox

Drug: Gemcitabine; Drug: 5-fluoro-uracil/oxaliplatin/leucovorin (folfox)

Interventions

ERY001 DRUG

Also known as: L asparaginase encapsulated in erythrocytes

standard of care combined with ERY001

Gemcitabine DRUG

standard of care alone; standard of care combined with ERY001

5-fluoro-uracil/oxaliplatin/leucovorin (folfox) DRUG

oxaliplatin 85 mg/m2 levo-leucovorin 200 mg/m2 5-FU 400 mg/m2

standard of care alone; standard of care combined with ERY001

Eligibility Criteria

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

You may qualify if:

• A patient is eligible for the study if all of the following criteria are met:
• Advanced or metastatic exocrine pancreatic adenocarcinoma, confirmed histologically
• Available archival tumor tissue block with sufficient tissue either from primary tumor and/or from metastatic lesions for biomarker testing; alternatively, unstained slides with sufficient tissue may be substituted
• Only 1 prior systemic therapy for advanced or metastatic disease. NOTE: Patient must be eligible to 2nd line gemcitabine or mFOLFOX6 treatment Documented disease progression during or following first-line therapy for advanced disease
• Measurable lesion (\>1cm) as assessed by CT scan or MRI (Magnetic Resonance Imaging) according to RECIST criteria (version 1.1)
• Age 18 years and older
• ECOG performance status 0 or 1
• Ability to understand, and willingness to sign, a written informed consent and to comply with the scheduled visits, treatment plans, laboratory tests, and other study procedures.
• Patient beneficiary of a Social Security Insurance if applicable

You may not qualify if:

• A patient is excluded from the study if any of the following criteria are met:
• Patient who have received Oxaliplatin in first line will not be eligible in FOLFOX arm; Patient who received Gemcitabine in first line will not be eligible in Gemcitabine arm
• Resectable pancreatic adenocarcinoma
• Known hypersensitivity to L-asparaginase or have had prior exposure to any form of L-asparaginase
• Anti-vitamin K treatment. Replacement with low molecular weight heparin treatment if required
• Inadequate organ functions:
• hemoglobin \< 9.0 g/dl, neutrophil count \< 1.5 x 109/L, platelets \< 100 x 109/L.
• Liver or pancreatic function abnormalities
• AST or ALT \> 3 x ULN, or
• Total bilirubin \> 1.5 x ULN, or
• Lipase \> 2 x ULN with suggestive clinical sign of pancreatitis or \> 3N without suggestive clinical sign
• Renal insufficiency: Renal clearance determined by the Cockroft and Gault Formula \< 60 mL/min
• Current or prior coagulopathy disorders in the last month
• PT ≥1.5 fold the upper limit of normal value or
• INR ≥1.5 fold the upper limit of normal value or

Sponsors & Collaborators

• ERYtech Pharma: lead

Study Sites (16)

Saint Catherine Institute

Avignon, 84918, France

Location

Institut de Cancerologie

Brest, 29609, France

Location

Hopital Beaujon

Clichy, 92118, France

Location

Hospital Henri Mondor

Créteil, 94010, France

Location

Groupe Hospitalier Mutualiste Grenoble

Grenoble, 38028, France

Location

Centre Hospitalier Departemental Vendee - Les Oudairies

La Roche-sur-Yon, 85925, France

Location

Centre Oscar Lambret

Lille, 59020, France

Location

Cnetre Leon Berard

Lyon, 69373, France

Location

Institut Regional du Cancer-Montpellier Val d'Aurelle

Montpellier, 34298, France

Location

Institute Mutualiste Montsouris

Paris, 75014, France

Location

Hospital Saint Antoine

Paris, 75571, France

Location

Hospital Pitie Salpetriere

Paris, 75651, France

Location

CHU de Poitiers

Poitiers, 42109, France

Location

CHU Reims

Reims, 51100, France

Location

CHU Toulouse - Rangueil

Toulouse, 31059, France

Location

CHU de Tours

Tours, 37044, France

Location

Related Publications (2)

• Bachet JB, Blons H, Hammel P, Hariry IE, Portales F, Mineur L, Metges JP, Mulot C, Bourreau C, Cain J, Cros J, Laurent-Puig P. Circulating Tumor DNA is Prognostic and Potentially Predictive of Eryaspase Efficacy in Second-line in Patients with Advanced Pancreatic Adenocarcinoma. Clin Cancer Res. 2020 Oct 1;26(19):5208-5216. doi: 10.1158/1078-0432.CCR-20-0950. Epub 2020 Jun 30.

  PMID: 32605910 DERIVED

• Hammel P, Fabienne P, Mineur L, Metges JP, Andre T, De La Fouchardiere C, Louvet C, El Hajbi F, Faroux R, Guimbaud R, Tougeron D, Bouche O, Lecomte T, Rebischung C, Tournigand C, Cros J, Kay R, Hamm A, Gupta A, Bachet JB, El Hariry I. Erythrocyte-encapsulated asparaginase (eryaspase) combined with chemotherapy in second-line treatment of advanced pancreatic cancer: An open-label, randomized Phase IIb trial. Eur J Cancer. 2020 Jan;124:91-101. doi: 10.1016/j.ejca.2019.10.020. Epub 2019 Nov 21.

  PMID: 31760314 DERIVED

MeSH Terms

Conditions

Adenocarcinoma; Neoplasms

Interventions

Erythrocyte Count; Gemcitabine; Folfox protocol

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Blood Cell Count; Cell Count; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Hematologic Tests; Investigative Techniques; Cell Physiological Phenomena; Blood Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Pascal Hammel, Pr MD

  Hopital Beaujon

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2014
• First Posted: July 21, 2014
• Study Start: July 1, 2014
• Primary Completion: February 1, 2017
• Study Completion: November 1, 2017
• Last Updated: July 27, 2018

Record last verified: 2017-11

Locations

FR (16)