Ensayos clínicos

Inclusion Criteria:

To be eligible for inclusion into the study patients must meet the following inclusion criteria:

• Histologically or cytologically confirmed adenocarcinoma of the pancreas that has not been previously treated in the metastatic setting: unresectable, locally advanced or metastatic disease is allowed, diagnosed within 6 weeks prior to Screening
• At least one tumor lesion measurable by CT or MRI scan (according to RECIST v1.1 criteria)
• ECOG performance status of 0 or 1 at Screening, and within 72 hours prior to first dose if first dose occurs more than 72 hours post screening. Two observers will be required to assess ECOG. If different, the lowest assessment will be used for the eligibility evaluation at each assessment (criterion applicable only for Part 1A).
• Adequate biological parameters as evidenced by all of the following blood counts:
  • Absolute neutrophil count (ANC) > 1,500 cells/μl without the use of hematopoietic growth factors within last 7 days prior to Screening;
  • Platelet count > 100,000 cells/μl;
  • Hemoglobin > 9 g/dL; transfusion is allowed, provided interval is ≥ 7 days prior to Screening.
• Adequate hepatic function as evidenced by:
  • Serum total bilirubin ≤ ULN (biliary drainage is allowed for biliary obstruction);
  • AST and ALT ≤ 2.5 x ULN (≤ 5 x ULN is acceptable if liver metastases are present).
• Adequate renal function as evidenced by serum creatinine ≤ 1.5 x ULN, and calculated clearance ≥60 mL/min/1.73 m2 for patients with serum creatinine levels above or below the institutional normal value. Actual body weight should be used for calculating creatinine clearance using the Cockcroft-Gault Equation (CreatClear = Sex * ((140 - Age) / (SerumCreat)) * (Weight / 72); for patients with body mass index (BMI) >30 kg/m2, lean body weight should be used instead.
• ECG without any clinically significant findings (e.g. QTc ≤450 ms for males and ≤470 ms for females and no known arrhythmias).
• Recovered from the effects of any prior surgery or radiotherapy.
• Able to understand and provide an informed consent.
• Patient has a Karnofsky performance status (KPS) ≥ 70 at Screening, and within 72 hours prior to date of first dose if first dose occurs more than 72 hours after screening. Two observers will be required to assess KPS. If discrepant, the one with the lowest assessment will be considered true (criterion applicable only for Part 1B, added in protocol Version 6.0).

Exclusion Criteria:

Patients must meet all the inclusion criteria listed above and none of the following exclusion criteria:

• Prior treatment of pancreatic cancer in the metastatic setting (or locally advanced setting) with surgery, radiotherapy, chemotherapy or investigational therapy (Note: palliative radiotherapy is permitted; placement of biliary stent is allowed).
• Prior treatment of pancreatic adenocarcinoma with chemotherapy in the adjuvant setting, except those where at least 12 months have elapsed since completion of the last dose and no persistent treatment-related toxicities are present.
• Uncontrolled CNS metastases (Note: Patients who require steroids should be on a stable or decreasing dose to be eligible).
• Clinically significant gastrointestinal disorder including hepatic disorders, bleeding, inflammation, occlusion, diarrhea > grade 1, malabsorption syndrome, ulcerative colitis, inflammatory bowel disease, or partial bowel obstruction.
• History of any second malignancy in the last 3 years; patients with prior history of in-situ cancer or basal or squamous cell skin cancer are eligible. Patients with a history of other malignancies are eligible if they have been continuously disease free for at least 3 years.
• Known hypersensitivity to any of the components of nal-IRI, other liposomal products, or any components of 5-FU, leucovorin or oxaliplatin.
• Concurrent illnesses that would be a relative contraindication to trial participation such as active cardiac or liver disease, including:
  • Severe arterial thromboembolic events (myocardial infarction, unstable angina pectoris, stroke) less than 6 months before inclusion;
  • NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure;
  • Known historical or active infection with HIV, hepatitis B, or hepatitis C.
• Active infection or an unexplained fever > 38.5°C during screening visits or on the first scheduled day of dosing (at the discretion of the investigator, patients with tumor fever may be enrolled), which in the investigator’s opinion might compromise the patient’s participation in the trial or affect the study outcome.
• Use of strong CYP3A4 inhibitors or inducers, or strong UGT1A1 inhibitors (patients are ineligible if unable to discontinue the use of strong CYP3A4 or UGT1A1 inhibitors at least 1 week or strong CYP3A4 inducers at least 2 weeks prior to receiving first dose of irinotecan liposome injection), or presence of any other contraindications for irinotecan.
  • See Section 6.8 for examples of strong CYP3A4 or UGT1A1 inhibitors or CYP3A4
• Presence of any contraindications for nal-IRI, 5-FU, leucovorin, or oxaliplatin.
• Any other medical or social condition deemed by the Investigator to be likely to interfere with a patient’s ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results.
• Pregnant or breast feeding; females of child-bearing potential must test negative for pregnancy within 7 days prior to the first dose based on a urine or serum pregnancy test. Both male and female patients of reproductive potential must agree to use a highly effective method of birth control, during the study and for 6 months following the last dose of study drug.
  • For a description of highly effective contraceptive measures, please see Appendix 1
• Neuroendocrine (carcinoid, islet cell) or acinar pancreatic carcinoma.
• Documented serum albumin <3 g/dL at Screening, and within 72 hours prior to first dose if first dose occurs more than 72 hours post screening (both labs at screening and prior to first dose may be confirmed locally).
• Patients who, in the opinion of the investigator, have symptoms or signs suggestive of clinically unacceptable deterioration of the primary disease at the time of screening.