Pancreatic Adenocarcinoma MedDRA version: 21.1 Level: LLT Classification code 10051971 Term: Pancreatic adenocarcinoma System Organ Class: 100000004864
Conditions
Interventions
Product Name: Eryaspase
Pharmaceutical Form: Dispersion for infusion
INN or Proposed INN: L-asparaginase encapsulated in red blood cells
Other descriptive name: L-ASPARAGINASE ENCAPSULATED IN RED BLO
Sponsors
ERYTECH Pharma
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A patient will be eligible for the study if all the following criteria are met: 1. Must be 18 years of age or older. 2. Must have histologically confirmed pancreatic adenocarcinoma. 3. Must have Stage III or IV disease (see Appendix 1). 4. Must have received one line of systemic chemotherapy in advanced setting with or without targeted agents, immunotherapy, or radiotherapy for treatment of advanced pancreatic adenocarcinoma. NOTE: patients whose disease progresses on, or within 3 months, of neo(adjuvant) chemotherapy may be considered eligible 5. Must have radiological evidence of disease progression following most recent prior treatment, defined as appearance of any new lesion or increase of >20% of one or more existing lesions. 6. Must have measurable lesion(s) per RECIST version 1.1 by CT scan with contrast (or MRI, if the patient is allergic to CT contrast media). - Measurable disease may be in the field of prior irradiation; however, at least 4 weeks must have elapsed between the completion of radiation therapy and the baseline scan documenting disease status. - Bone disease is considered radiologically measurable only if there is at least a 50% lytic component. NOTE: Bone disease consisting of blastic lesion only is not measurable. 7. Archival or fresh tumor tissue must be available for evaluating relevant biomarkers. Formalin-fixed paraffin-embedded [FFPE] block preferred, or a minimum of 10 unstained FFPE slides of one archived block is required. NOTE: Cytology samples from fine needle aspirates or brushing biopsies are not sufficient. NOTE: if archival tissue is unavailable and an elective biopsy can’t be scheduled due to COVID, this will be waived 8. Must have adequate performance status: - ECOG Performance Status (PS) score of 0, or - ECOG score 1 and score =80 on Karnofsky Performance Status (KPS) scale. NOTE: Must have body mass index (BMI) =18.5 kg/m2 (obtained 12 weeks according to the Investigator’s clinical judgment. 10. Females of childbearing potential must have a negative pregnancy test at screening and additional negative pregnancy test prior to first dose. Males and females of childbearing potential must agree to use a highly effective method of contraception during treatment and for at least 6 months after the last dose of study treatment. These include, but not limited to: a. combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: i. intravaginal ii. transdermal b. progestogen-only hormonal contraception associated with inhibition of ovulation: i. injectable ii. implantable c. intrauterine device (IUD) d. bilateral tubal occlusion e. vasectomised partner f. sexual abstinence (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments) is intended. g. males with partners of childbearing potential must agree to use condoms NOTE: Since an indirect interaction between components of the oral contraceptives and ASNase cannot be ruled out, oral contraceptives are not considered acceptable as contraceptive methods in the current clinical trial. A method other than oral contraception should be used in women of childbearing potential. NOTE: All chemotherapeutic agents may be teratogenic and excreted in breast milk. Patients who are breast feeding should consider alternative methods. 11. Must have adequate laboratory parameters at
Exclusion criteria
Exclusion criteria: A patient is not eligible to participate in the study if any of the following criteria are met: 1. Resectable or borderline resectable pancreatic adenocarcinoma at the time of signing the informed consent. 2. Histology other than pancreatic adenocarcinoma (for example, but not inclusive: neuroendocrine, adenosquamous). 3. More than one line of prior treatment in advanced or metastatic setting. 4. Patient has experienced medically significant acute decline in clinical status including a. Decline in ECOG PS to >1 (or KPS Grade 2 at baseline. 10. Pregnancy or breastfeeding. 11. History of infection with human immunodeficiency virus (HIV) and/or active infection with hepatitis B or hepatitis C. NOTE: Patients with unknown status of hepatitis B or C must be tested and declared negative before randomization. 12. Hypersensitivity to any of the components of the chemotherapy or asparaginase. NOTE: Patients known to be homozygous for UGT1A1*28 who are assigned to an irinotecan-containing regimen must have the initial irinotecan dose reduced unless they have previously tolerated full doses of irinotecan. Subjects whose UGT1A1 status is not known but are being considered for irinotecan-based chemotherapy must be screened for UGT1A1*28 allele unless they have previously tolerated full doses of irinotecan before enrollment into the trial and must have the initial irinotecan dose reduced if demonstrated to be homozygous for the UGT1A1*28 allele. NOTE: Patients assigned to the irinotecan/5 FU arms in the study should not have dihydropyridine dehydrogenase deficiency (DPD). Patients whose DPD status is unknown at time of screening should be tested before enrollment in the irinotecan/5 FU arm unless they have previously tolerated full doses of 5 FU. 13. Patients who have received live or live attenuated vaccines within 3 weeks of randomization. 14. History of other malignancies NOTE: Adequately treated non-melanoma skin cancer or curatively treated in-situ cancer of the cervix may be eligible. NOTE: Patients successfully treated for other malignancies and are disease-free for at least 5 years may be eligible. 15. Any other severe acute or chronic condition/treatments that may increase the risk of study participation including: a. History of abdominal fistula, gastro
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to determine whether the addition of eryaspase to chemotherapy improves overall survival (OS) in second-line treatment of pancreatic adenocarcinoma compared to chemotherapy alone.;Secondary Objective: The secondary objectives of this study: To compare progression-free survival (PFS) between the 2 treatment arms. To compare the objective response rate (ORR) and duration of response (DoR) between the 2 treatment arms. To compare the disease control rate (DCR) between the 2 treatment arms.To evaluate the safety and tolerability of eryaspase in combination with chemotherapy versus chemotherapy alone. To assess the effect of eryaspase on quality of life using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). To determine the pharmacokinetics of eryaspase. To assess the immunogenicity of eryaspase in terms of the induction of anti-asparaginase antibodies and neutralizing antibodies. To evaluate the relationship of clinical outcome with relevant biomarkers and genetic changes present in tumor tissues and blood and/or serum samples. To investigate the predictive relationship between the patient’s DNA sequence variation.;Primary end point(s): The primary objective of this study is to determine whether the addition of eryaspase to chemotherapy improves overall survival (OS) in second-line treatment of pancreatic adenocarcinoma compared to chemotherapy alone.;Timepoint(s) of evaluation of this end point: To be measured from the date of randomization to the date of death from any cause. Patients who are not known to have died will be censored at the date of last contact, and this will apply as of the date of data cut-off for any particular analysis. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary objectives of this study are: - To compare progression-free survival (PFS) between the 2 treatment arms. - To compare the objective response rate (ORR) and duration of response (DoR) between the 2 treatment arms. - To compare the disease control rate (DCR) between the 2 treatment arms. - To evaluate the safety and tolerability of eryaspase in combination with chemotherapy versus chemotherapy alone. - To assess the effect of eryaspase on quality of life using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). - To determine the pharmacokinetics of eryaspase. - To assess the immunogenicity of eryaspase in terms of the induction of anti-asparaginase antibodies and neutralizing antibodies. - To evaluate the relationship of clinical outcome with relevant biomarkers and genetic changes present in tumor tissues and blood and/or serum samples. - To investigate the predictive relationship between the patient’s DNA sequence variation, e.g. exploratory SNP genotyping and their response to combination treatment in terms of safety and tolerability (pharmacogenetics [PGx]).;Timepoint(s) of evaluation of this end point: PFS will be compared between the 2 treatment arms using the same methods of analysis as for OS. | — |
Countries
Austria, Belgium, Czechia, Denmark, Finland, France, Germany, Italy, Netherlands, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactIman El-Hariry
ERYTECH Pharma
Outcome results
None listed