Clinical trial NCT02195180: Efficacy and Safety of L-asparaginase Encapsulated in RBC Combined With Gemcitabine or FOLFOX in 2nd Line for Progressive Metastatic Pancreatic Carcinoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pancreatic Adenocarcinoma Metastatic
Keywords: Pancreas
adenocarcinoma
cancer
asparaginase
erythrocytes
red blood cell
Encapsulation
folfox
gemcitabine
Lead sponsor: ERYtech Pharma
Sponsor class: INDUSTRY
First posted: 2014-07-21
Enrollment: 141
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Overall survival (OS)
timeFrame: From last study treatment assessment visit until patient's death, loss to follow up, or study closure, assessed up to 36 months.
measure: Progression free survival (PFS)
timeFrame: 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:
measure: Incidence of Treatment Emergent Adverse Events (Safety and Tolerability)
timeFrame: collected from time of informed consent until 4 weeks after last study treatment
measure: Overall survival
timeFrame: From last study treatment assessment visit until patient's death, loss to follow up, or study closure, assessed up to 36 months.
measure: Progression free survival
timeFrame: 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.
measure: Objective response rate (ORR)
timeFrame: From date of randomization to last tumor assessment data collected for each patient, assessed up to 24 months.
measure: Disease control rate (DCR)
timeFrame: From date of randomization to 16 and 24 weeks.
measure: Duration of response (DoR)
timeFrame: From date of first response of complete or partial response until tumor progression, assessed up to 24 months.
measure: Evaluate the relationship of clinical outcomes with tumor markers
timeFrame: From date of randomiztion to end of treatment visit, assessed up to 20 months.
measure: Optical density reading
timeFrame: 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.
measure: Quality of Life status
timeFrame: From date of randomiztion to end of treatment visit, assessed up to 20 months.
Other outcomes:
Locations:
city: Avignon
country: France
facility: Saint Catherine Institute
city: Brest
country: France
facility: Institut de Cancerologie
city: Clichy
country: France
facility: Hopital Beaujon
city: Creteil
country: France
facility: Hospital Henri Mondor
city: Grenoble
country: France
facility: Groupe Hospitalier Mutualiste Grenoble
city: La Roche-sur-Yon
country: France
facility: Centre Hospitalier Departemental Vendee - Les Oudairies
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lyon
country: France
facility: Cnetre Leon Berard
city: Montpellier
country: France
facility: Institut Regional du Cancer-Montpellier Val d'Aurelle
city: Paris
country: France
facility: Institute Mutualiste Montsouris
city: Paris
country: France
facility: Hospital Saint Antoine
city: Paris
country: France
facility: Hospital Pitie Salpetriere
city: Poitiers
country: France
facility: CHU de Poitiers
city: Reims
country: France
facility: CHU Reims
city: Toulouse
country: France
facility: CHU Toulouse - Rangueil
city: Tours
country: France
facility: CHU de Tours
Study officials:
affiliation: Hopital Beaujon
name: Pascal Hammel, Pr MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.