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

July 25, 2018 updated by: ERYtech Pharma

Phase II, Randomized, Controlled, Clinical Trial Exploring Efficacy and Safety of ERY001 (L-asparaginase Encapsulated in Red Blood Cells) in Association With Gemcitabine or FOLFOX4 in Second-line Therapy for Patients With Progressive Metastatic Pancreatic Carcinoma

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

141

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Avignon, France, 84918
        • Saint Catherine Institute
      • Brest, France, 29609
        • Institut de Cancérologie
      • Clichy, France, 92118
        • Hopital Beaujon
      • Creteil, France, 94010
        • Hospital Henri Mondor
      • Grenoble, France, 38028
        • Groupe Hospitalier Mutualiste Grenoble
      • La Roche-sur-Yon, France, 85925
        • Centre Hospitalier Departemental Vendee - Les Oudairies
      • Lille, France, 59020
        • Centre Oscar Lambret
      • Lyon, France, 69373
        • Cnetre Leon Berard
      • Montpellier, France, 34298
        • Institut Regional du Cancer-Montpellier Val d'Aurelle
      • Paris, France, 75014
        • Institute Mutualiste Montsouris
      • Paris, France, 75571
        • Hospital Saint Antoine
      • Paris, France, 75651
        • Hospital Pitie Salpetriere
      • Poitiers, France, 42109
        • CHU de Poitiers
      • Reims, France, 51100
        • CHU Reims
      • Toulouse, France, 31059
        • CHU Toulouse - Rangueil
      • Tours, France, 37044
        • CHU de Tours

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: standard of care combined with ERY001
standard of care = Gemcitabine or folfox
Drug: Gemcitabine
Drug: ERY001
Other Names:
  • L asparaginase encapsulated in erythrocytes
Drug: 5-fluoro-uracil/oxaliplatin/leucovorin (folfox)
oxaliplatin 85 mg/m2 levo-leucovorin 200 mg/m2 5-FU 400 mg/m2
Sham Comparator: standard of care alone
standard of care = Gemcitabine or folfox
Drug: Gemcitabine
Drug: 5-fluoro-uracil/oxaliplatin/leucovorin (folfox)
oxaliplatin 85 mg/m2 levo-leucovorin 200 mg/m2 5-FU 400 mg/m2

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival (OS)
Time Frame: From last study treatment assessment visit until patient's death, loss to follow up, or study closure, assessed up to 36 months.
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)
Time Frame: 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.
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Treatment Emergent Adverse Events (Safety and Tolerability)
Time Frame: collected from time of informed consent until 4 weeks after last study treatment
Compare the safety profile in patients treated with eryaspase in combination with chemotherapy versus chemotherapy alone, including adverse events, vital signs and clinical laboratory assessments
collected from time of informed consent until 4 weeks after last study treatment
Overall survival
Time Frame: From last study treatment assessment visit until patient's death, loss to follow up, or study closure, assessed up to 36 months.
Evaluate the effects of eryaspase in combination with chemotherapy on investigator-assessed OS in all randomized patients (all patients) and in patients with ASNS 2+/3+ expressing tumors.
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
Time Frame: 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.
Evaluate the effects of eryaspase in combination with chemotherapy on investigator-assessed PFS in all randomized patients (all patients) and in patients with ASNS 2+/3+ expressing tumors.
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)
Time Frame: From date of randomization to last tumor assessment data collected for each patient, assessed up to 24 months.
Evaluate the effect of eryaspase in combination with chemotherapy on the ORR, and the duration in all comers, patients with ASNS 0/1+ expressing tumors, and those with ASNS 2+/3+ expressing tumors.
From date of randomization to last tumor assessment data collected for each patient, assessed up to 24 months.
Disease control rate (DCR)
Time Frame: From date of randomization to 16 and 24 weeks.
Evaluate the effect of eryaspase in combination with chemotherapy on the DCR in all comers, patients with ASNS 0/1+ expressing tumors, and those with ASNS 2+/3+ expressing tumors.
From date of randomization to 16 and 24 weeks.
Duration of response (DoR)
Time Frame: From date of first response of complete or partial response until tumor progression, assessed up to 24 months.
Evaluate the effect of eryaspase in combination with chemotherapy on the DoR in all comers, patients with ASNS 0/1+ expressing tumors, and those with ASNS 2+/3+ expressing tumors.
From date of first response of complete or partial response until tumor progression, assessed up to 24 months.
Evaluate the relationship of clinical outcomes with tumor markers
Time Frame: From date of randomiztion to end of treatment visit, assessed up to 20 months.
Evaluate the relationship of clinical outcome (i.e. OS, PFS, ORR, DCR and DoR) with tumor markers, namely cancer antigen (CA19-9), and carcinoembryonic antigen test (CEA).
From date of randomiztion to end of treatment visit, assessed up to 20 months.
Optical density reading
Time Frame: 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.
Assess the effect of eryaspase in combination with chemotherapy on PFS, OS, ORR, BOR, and other clinical outcomes in ASNS subsets, as determined by optical density reading.
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.
Quality of Life status
Time Frame: From date of randomiztion to end of treatment visit, assessed up to 20 months.
Compare the 2 treatment arms with respect to change in quality of life status, the change of QOL relative to baseline
From date of randomiztion to end of treatment visit, assessed up to 20 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

ERYtech Pharma

Investigators

  • Principal Investigator: Pascal Hammel, Pr MD, Hopital Beaujon

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2014

Primary Completion (Actual)

February 1, 2017

Study Completion (Actual)

November 1, 2017

Study Registration Dates

First Submitted

July 16, 2014

First Submitted That Met QC Criteria

July 17, 2014

First Posted (Estimate)

July 21, 2014

Study Record Updates

Last Update Posted (Actual)

July 27, 2018

Last Update Submitted That Met QC Criteria

July 25, 2018

Last Verified

November 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GRASPANC 2013-03
  • 2013-004262-34 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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