Clinical study in subjects with pancreatic adenocarcinoma to assess safety and efficacy of investigational product (eryaspase) when added to standard chemotherapy

Phase 1

• Conditions: Pancreatic Adenocarcinoma; MedDRA version: 20.0 Level: LLT Classification code 10051971 Term: Pancreatic adenocarcinoma System Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-000572-15-DK
• Lead Sponsor: ERYTECH Pharma

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-08-27
• Last Update Posted: 30 June 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 602

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 ductal adenocarcinoma.
3. Must have Stage III or IV disease (see Appendix 11.1).
4. Must have received only one line of systemic chemotherapy with or without targeted agents, immunotherapy, or radiotherapy for treatment of advanced pancreatic
adenocarcinoma.
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.
8. Must have adequate performance status (see Appendix 11.2):
- ECOG Performance Status (PS) score of 0, or
- ECOG score 1 and score =80 on Karnofsky Performance Status (KPS) scale.
9. Must have life expectancy of >12 weeks according to the Investigator’s clinical judgment.
10. Females of childbearing potential must have a negative pregnancy test at screening and additional 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.
11. Must have adequate laboratory parameters at baseline (obtained <14 days prior to randomization:
a. Absolute neutrophil count =1.5 x 109/L.
b. Hemoglobin =9 g/dL.
c. Platelet count =100,000/mm3 (100 x 109/L).
d. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =2.5 x upper limit of normal (ULN) (=5 x ULN in presence of liver metastases).
e. Total bilirubin =1.5 x institutional ULN.
f. Serum creatinine within normal limits or calculated clearance >60 mL/min/1.73 m2 for patients with serum creatinine levels above or below the
institutional normal range. Actual body weight should be used for calculating creatinine clearance (e.g., using the Cockcroft-Gault formula). For patients with a
Body Mass Index (BMI) >30 Kg/m2, lean body weight should be used instead.
g. Acceptable coagulation parameters: plasma antithrombin III >70%, fibrinogen =1.5 g/dL, international normalized ratio (INR) <1.5, and partial thromboplastin
time (PTT) =

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.
2. Histology other than pancreatic ductal adenocarcinoma (for example, but not inclusive: neuroendocrine, adenosquamous).
3. More than 1 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 <70) between baseline visit and within 72 hours prior to randomization.
b. Weight loss of =10% during screening.
5. Presence of active or symptomatic untreated central nervous system (CNS) metastases.
NOTE: Patients with asymptomatic or stable CNS metastases are eligible, provided that the CNS metastases are radiologically and clinically stable, and the patient is off steroids for at least 1 month prior to randomization.
6. Prior radiotherapy to the only area of measurable disease, unless there is documented disease progression, defined as an increase of at least 1 cm in the longest diameter compared to the nadir scan.
NOTE: Patients must have completed treatment and recovered from all acute treatmentrelated toxicities prior to administration of the first dose of eryaspase or chemotherapy.
7. Bone as the only site of metastatic disease from pancreatic cancer (bone-only disease).
8. History of recent clinical pancreatitis, according to revised Atlanta criteria, within 3 months of randomization.
NOTE: The revised Atlanta classification [1] requires that two or more of the following criteria be met for the diagnosis of acute pancreatitis: (a) abdominal pain suggestive of
pancreatitis, (b) serum amylase or lipase level =3 x ULN, or (c) characteristic imaging findings using CT or MRI.
9. Neurosensory neuropathy >Grade 1 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.
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. Subjects whose UGT1A1 status is not known but are being considered for irinotecan-based
chemotherapy must be screened for UGT1A1*28 allele before enrollment into the trial and must have the initial irinotecan dose reduced if demonstrated to be homozygous for the UGT1A1*28 allele.
13. Patients being treated with warfarin are not eligible. Warfarin must be replaced with low molecular weight heparin.
14. History of other malignancies except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumors curatively treated by
surgery alone or surgery plus radiotherapy with no evidence of disease for >5 years.
15. Any other severe acute or chronic condition that may increase the risk of study participation including:
a. History of abdominal fistula, gastrointestinal perforat

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified