A Randomized, Phase 3 Study of Eryaspase in Combination with Chemotherapy versus Chemotherapy Alone as Second-Line Treatment in Patients with Pancreatic Adenocarcinoma
- Conditions
- Pancreatic AdenocarcinomaPancreatic cancer10017991
- Registration Number
- NL-OMON55526
- Lead Sponsor
- ERYTECH Pharma
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 10
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 Protocol Appendix 1).
4. Must have received only 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
progression 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 (see Protocol Appendix 2 and 3):
- ECOG Performance Status (PS) score of 0, or
- ECOG score 1 and score >=80 on Karnofsky Performance Status (KPS) scale.
Must have body mass index (BMI) >=18.5 kg/m2 (obtained <14 days prior to
randomization
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. For more details see protocol
11. Must have adequate laboratory parameters at baseline (obtained <14 days
prior to randomization:Laboratory parameters outside of these ranges that are
deemed clinically insignificant should be discussed with the medical monitor
a. Absolute neutrophil count >=1.5 x 109/L.
b. Hemoglobin >=9 g/dL. monitorPatients with a baseline Hemoglobin >=13 g/dL
should be discussed with the medical monitor
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.
g. Acceptable coagulation parameters: plasma antithrombin III >70%, and
fibrinogen >=1.5 g/L, international normalized ratio (INR) <1.5, and par
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 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 high dose steroids treatment for at least 1 month prior to
randomization.
6. Prior radiotherapy to the only area of measurable disease 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.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 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 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 nonmelanoma 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/treatment that
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary analysis will be the comparison of OS between the 2 treatment arms<br /><br>in the ITT population using the 2-sided stratified log-rank test, stratified<br /><br>for ECOG status, chemotherapy regimen, and time from diagnosis of advanced<br /><br>disease.<br /><br><br /><br>The primary efficacy endpoint is Overall Survival (OS) and the study is<br /><br>designed to test the superiority of eryaspase plus chemotherapy over<br /><br>chemotherapy alone. The primary analysis will test the following hypotheses:<br /><br>• Null Hypothesis: The hazard ratio for OS between eryaspase plus chemotherapy<br /><br>and chemotherapy alone is equal to one<br /><br>• Alternative Hypothesis: The hazard ratio for OS between eryaspase plus<br /><br>chemotherapy and chemotherapy alone is less than one</p><br>
- Secondary Outcome Measures
Name Time Method