| Eligibility |
Inclusion Criteria:
1. Age 18 to 70 years old (inclusive), regardless of gender;
2. Histologically or cytologically confirmed unresectable, locally advanced, or
metastatic pancreatic adenocarcinoma;
3. At least one measurable lesion according to RECIST 1.1.
4. No prior systemic anti-tumor therapy, except those with disease progression more than
6 months after adjuvant therapy or neoadjuvant therapy;
5. Patients with prior local treatment (radical radiotherapy or radical
chemoradiotherapy, etc.) may be enrolled provided that the local treatment does not
involve the target lesion, or the target lesion is within the treatment area, but the
size has increased more than 20% since the post-treatment evaluation, and also must be
completed at least 4 weeks before the first administration of the study drug,
palliative decompensated radiotherapy (such as bone metastases) must be completed at
least 2 weeks before the first administration of the study drug;
6. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1;
7. Life expectancy >3 months;
8. Adverse reactions must recover to grade 1 or baseline according to CTCAE 5.0 (except
for toxicity such as alopecia, grade 2 or less sensory neuropathy, etc., which have
been judged no safety risk by investigators).
9. Patients should not receive cell growth factors or blood and platelet transfusion
within 7 days before the initiate administration of study drug, and laboratory test
must meet the following criteria:
neutrophile count =1.5×10^9/L; platelet count =100×10^9/L; hemoglobin =90 g/L or =5.6
mmol/L; serum creatinine =1×ULN or creatinine clearance rate must be = 50 mL/min when
serum creatinine >1.0×ULN; total bilirubin =1.5×ULN; aspartate aminotransferase (AST)
and alanine aminotransferase (ALT) =2.5×ULN or =5×ULN if intrahepatic lesions exist;
Albumin =3 g/dL.
10. Activated Partial Thromboplastin Time (APTT), International Normalized Ratio (INR) and
prothrombin time (PT) =1.5 × ULN for patients not receiving therapeutic
anticoagulation.
11. According to the related guidelines, patients with HBV DNA or HBsAg and/or anti-HBC
positive must receive prophylactic treatment (at least one week before the initial
administration of the study drug) and take antiviral drugs in stable dose (e.g.,
entecavir, tenofovir, or lamivudine; No adefovir or interferon are allowed) at study
entry with planned monitoring and management, including baseline HBV DNA levels.
Patient receiving active hepatitis C virus (HCV) treatment must use astable dose of
drugs at study entry and be subject to planned monitoring and management according to
antiviral drug guidelines;
12. Female patients with reproductive potential must agree to use adequate contraception
from the signing of informed consent to at least 6 months after the study completion
and have a negative serum pregnancy test within 3 days before enrollment, and must be
non-lactating. Male patients must agree to use medically approved contraception during
the study period and for 6 months after the study completion;
13. Ability to understand and the willingness to sign a written informed consent.
Exclusion Criteria:
1. Patients with acinar cell carcinoma, pancreatoblastoma, solid pseudopapillary tumor
and pancreatic neuroendocrine tumor;
2. Patients with definitive diagnosis of CNS metastasis;
3. Patients with hepatic encephalopathy at screening;
4. Patients with clinically symptomatic ascites requiring puncture or drainage or who
have received ascites drainage within the past 3 months, except for those with only a
small amount of ascites on imaging but no clinical symptoms;
5. Uncontrolled third lacunar effusion other than ascites (e.g., large pleural or
pericardial effusion) within 4 weeks before the first administration of the test drug;
6. Previous malignancies in the past five years (except radically resected and
non-recurring basal cell carcinoma of the skin, squamous cell carcinoma of the skin,
superficial bladder carcinoma, local prostate carcinoma, carcinoma in situ of
cervical, or other carcinoma in situ);
7. Patients with partial or complete biliary obstruction who has not relieved by active
treatment;
8. History of serious cardiovascular disease, including but not limited to:
1) Acute myocardial infarction, unstable angina pectoris, coronary angioplasty, stroke,
severe pulmonary embolism; 2) New York Heart Association class grade III or IV congestive
heart failure or left ventricular ejection fraction (LVEF) < 50%; 3) Poorly controlled
hypertension (systolic blood pressure = 150 mmHg and/or diastolic blood pressure= 95 mmHg)
with optimal treatment; 4) Ventricular arrhythmia; 5) Patients with prolonged QT/QTc
interval in baseline electrocardiogram (ECG) (QTcF > 480 ms, Fridericia formula: QTcF =
QT/(RR^0.33), RR = 60/heart rate); 6) Patients with clinically significant abnormal
electrocardiogram (ECG) according to the investigator's assessment.
9.Patients with uncontrolled active bleeding.
10.Patients with known interstitial lung disease;
11.Patients with known peripheral neuropathy (CTCAE grade 3 or 4);
12.Patients with severe lung, liver, kidney, endocrine, immune system, skin or
musculoskeletal diseases within 3 months prior to the first dose and who are not suitable
for enrollment in the opinion of the investigator;
13.Patients who are at risk of active infection or have active infection that may affect
the results of the study (such as severe pneumonia requiring hospitalization, bacteremia,
acute bacterial infection, infectious complications, tuberculosis, active HIV infection,
etc.) or who, in the judgment of the investigator, are not suitable for participation in
this clinical trial. Active hepatitis B virus is defined as HBV DNA=10^4 copies or = 2000
IU/mL; active hepatitis C virus or active HIV infection is defined as HCV-RNA positive;
14.Gastrointestinal diseases of clinical significance, such as bleeding, inflammation,
obstruction, >grade 1 diarrhea, malabsorption syndrome, diseases significantly affecting
gastrointestinal function, gastric or small bowel resection, etc;
15.Patients with known to have dihydropyrimidine dehydrogenase (low activity) or
deficiency;
16.Patients with definite Gilbert syndrome;
17.History of explicit neurological or psychiatric disorders, including epilepsy or
dementia;
18.Patients with known alcohol or drug dependence.
19.Patients who have concomitant use of strong CYP3A4 inducers within 2 weeks prior to the
first dose, or strong CYP3A4 inhibitors or strong UGT1A1 inhibitors within 1 week prior to
the first dose;
20.Patients who have required systemic glucocorticoids (prednisone >10 mg/day or equivalent
dose of the similar drugs) or other immunosuppressive agents within 14 days before the
first dose of the study drug. Except for treatment with local, ocular, intra-articular,
intranasal, and inhaled glucocorticoids in the absence of active autoimmune disease,
short-term preventive treatment with glucocorticoids (e.g., prevention of contrast
allergy);
21.Patients who have major organ surgery (except for needle biopsy, central venous
catheterization, port-cath, stenting to relieve biliary obstruction, and percutaneous
hepatic biliary drainage, cholecystostomy) or selective operation plan were performed
within 4 weeks before the first dose of the study drug;
22.Patients with known allergy to irinotecan liposome injection, other liposome products,
oxaliplatin, 5-fluorouracil, leucovorin, Nab-paclitaxel, other albumin products,
gemcitabine or any of the ingredients in the above products.;
23. Patients who are not suitable for this study as determined by the investigator.
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