Pancreatic cancer MedDRA version: 16.1 Level: LLT Classification code 10051971 Term: Pancreatic adenocarcinoma System Organ Class: 100000004864
Conditions
Interventions
Product Code: ERY001
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: L-asparaginase encapsulated in erythrocytes
Current Sponsor code: L-asparaginase encapsulated in erythrocytes
Co
Sponsors
ERYTECH Pharma
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Patients with progressive metastatic exocrine pancreatic adenocarcinoma, confirmed histologically - Patients with available histology specimen, either from primary tumor and/or from metastatic lesions. The IHC analyses (done in a central laboratory) issued from these specimens MUST allow determining the level of asparagine synthetase expression. Such result is mandatory for the final analysis - Patient eligible to 2nd line gemcitabine or FOLFOX4 treatment according investigator’s decision. - Measurable lesion (>1cm) as assessed by CT scan or MRI (Magnetic Resonance Imaging) according to RECIST criteria (version 1.1) - Patient aged 18 years and older - ECOG (WHO) performance status 0-1 - Signed Informed Consent - Patient beneficiary of a Social Security Insurance if applicable During the selection period, any study related examination not required for the standard diagnosis must be performed after signature of the informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 60 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: - Patient with cerebral metastasis - Patient with resectable or borderline non metastatic pancreatic adenocarcinoma - Patient with 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 - Patient unable to receive treatments based on gemcitabine or FOLFOX4 or ERY001, due to general or visceral conditions unrelated to pancreatic cancer such as: * Bone marrow impairment as evidenced by hemoglobin 3 x ULN, or Total bilirubin > 1.5 x ULN, or Lipase > 2N (grade 2) with suggestive clinical sign 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 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 * 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 - 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, 30 days prior inclusion - Women of child-bearing potential and men with partners of childbearing potential without effective contraception as well as pregnant or breast feeding women. - Patients whose regular follow-up is impossible due to psychological, family, social or geographical reasons
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to determine the potential improvement of Progression Free Survival (PFS) rate at 16 weeks with ERY001 combined with gemcitabine or FOLFOX4 chemotherapy, in a population of patients with progressive metastatic pancreatic adenocarcinoma, after progression under a first line of chemotherapy, over 18 years.;Secondary Objective: Secondary - Assess the overall tolerance of ERY001 in combination with gemcitabine or FOLFOX4 chemotherapy as second line of chemotherapy. - Evaluate tumor response through clinical and biological markers over time - Evaluate PK/PD and immunogenicity parameters of ERY001 - Evaluate treatment adherence - Assess potential association between response and ASNS expression level (no or weak) on tumor - Evaluation of the Quality of Life Exploratory - To assess circulating tumor DNA: The aim is to assess the predictive value of circulating tumor DNA variations during the course of treatment. All patients will be eligible for circulating tumor DNA analysis. - To assess tumor responses by using new imaging methods and new tumor assessments criteria;Primary end point(s): PFS rate of ASNS 0-1 patients with ERY001 at Month 4 (week 16). Progression is defined as per local evaluation as: - appearance of one or more new lesions, - increase in the size of target measurable lesions (greater than or equal to 20% of the sum of the largest diameters according to RECIST criteria version 1.1) Progression-free survival is defined as the time from randomization to time of objective disease progression or death related to medical condition. Medical images will be centrally reviewed. These central reads RECIST data will be supportive only and will be performed as sensitivity analysis.;Timepoint(s) of evaluation of this end point: Timepoint(s) of evaluation of Primary end points are described in E.5.1 | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Timepoint(s) of evaluation of Secondary end points are described in E.5.2;Secondary end point(s): Secondary endpoints: - Overall tolerance of the Frequency, severity and relationship to study treatments drug of AE - Time to progression, (TTP), disease control rate, and survival rates over time up to 24 weeks, (DCR), overall survival (OS),) and event free survival (EFS) over time up to 24 weeks: * Time to progression is defined as the time from randomization to time of objective disease progression. * Disease control rate is defined as the percentage of patients who achieved disease control overtime following randomization. Disease control at 24 weeks is defined as a best objective response of Complete Response (CR), Partial (PR) or stable disease (SD = 24) per RECIST criteria (version 1.1) (MRI/CT scan every 8 weeks or sooner if clinically indicated). * Objective response rate defined as complete or partial response (CR or PR) per RECIST criteria (version 1.1) (MRI/CT scan every 8 weeks or sooner if clinically indicated) * Overall survival defined as the time elapsed between randomization and death from any cause * Event free survival defined as the time elapsed between randomization and disease progression, or treatment stop/delayed from toxicity reason, or death from any cause Patients who are alive without disease progression by the clinical cut-off will be censored at the dates of their last tumor evaluation. - Pharmacokinetic (PK) / pharmacodynamic parameters evaluation of ERY001 including * Pharmacokinetic parameters: Blood activity of free, total, plasmatic and encapsulated L-asparaginase * Pharmacodynamic parameters: Plasmatic concentrations of amino-acids (asparagine, aspartate, glutamine, and glutamate; ); Percentage of patient presenting with asparagine depletion at different time points (i.e. = 2µM); * Percentage of deamination compared to baseline levels; * Immunogenicity: titers of Anti-L | — |
Countries
France
Contacts
Public ContactJerome Bailly
ERYTECH Pharma
Outcome results
None listed