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

NCT ID: NCT02195180

Last Updated: 2018-07-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 141 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-07-31
• Study Completion Date: 2017-11-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

standard of care combined with ERY001

standard of care = Gemcitabine or folfox

Group Type: EXPERIMENTAL

ERY001

Intervention Type: DRUG

Gemcitabine

Intervention Type: DRUG

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

Intervention Type: DRUG

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

standard of care alone

standard of care = Gemcitabine or folfox

Group Type: SHAM_COMPARATOR

Gemcitabine

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Interventions

ERY001

Intervention Type: DRUG

Gemcitabine

Intervention Type: DRUG

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

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

Intervention Type: DRUG

Other Intervention Names

L asparaginase encapsulated in erythrocytes

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

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
• Fibrinogen ≤ 0.75 fold the lower limit of normal value
• Known Infection: HIV, active hepatitis related to B or C virus
• Concurrent active malignancies (with the exception of in situ carcinoma of the cervix and inactive non melanoma skin cancer
• Other serious conditions than pancreatic cancer according to investigator's opinion
• NYHA Grade ≥ 2 congestive heart failure
• Systemic chemotherapy or radiation within the last 3 weeks or major surgery within 4 weeks NOTE: chemotherapy or radiation therapy given in less than 3 weeks is allowed, provided patient recovered from all related toxicities
• History of grade 3 blood transfusion reaction (life threatening situation)
• Presence of anti-erythrocyte antibodies (auto-antibodies or anti-public antibodies) preventing from getting a compatible packed Red Blood Cells for the patient
• Participation in another concurrent clinical trial
• Women of child-bearing potential and men with partners of childbearing potential without effective contraception as well as pregnant or breast feeding women
• Other severe acute/chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the Investigator would make the patient inappropriate for entry into this study.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ERYtech Pharma

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pascal Hammel, Pr MD

Role: PRINCIPAL_INVESTIGATOR

Hopital Beaujon

Locations

Saint Catherine Institute

Avignon, , France

Institut de Cancerologie

Brest, , France

Hopital Beaujon

Clichy, , France

Hospital Henri Mondor

Créteil, , France

Groupe Hospitalier Mutualiste Grenoble

Grenoble, , France

Centre Hospitalier Departemental Vendee - Les Oudairies

La Roche-sur-Yon, , France

Centre Oscar Lambret

Lille, , France

Cnetre Leon Berard

Lyon, , France

Institut Regional du Cancer-Montpellier Val d'Aurelle

Montpellier, , France

Institute Mutualiste Montsouris

Paris, , France

Hospital Saint Antoine

Paris, , France

Hospital Pitie Salpetriere

Paris, , France

CHU de Poitiers

Poitiers, , France

CHU Reims

Reims, , France

CHU Toulouse - Rangueil

Toulouse, , France

CHU de Tours

Tours, , France

Countries

France

References

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.

Reference Type: DERIVED

PMID: 32605910 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31760314 (View on PubMed)

Other Identifiers

2013-004262-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GRASPANC 2013-03

Identifier Type: -

Identifier Source: org_study_id