Ensayos clínicos

Inclusion Criteria:

• Subject has been informed about the nature of the study, and has agreed to participate in the study, and signed the informed consent form (ICF) prior to participation in any study-related activities.
• Male or non-pregnant and non-lactating female and ≥ 18 years of age:
  • Females of child-bearing potential (i.e., fertile, following menarche and until becoming postmenopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy) must test negative for pregnancy at the time of screening based on a urine or serum pregnancy test. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. Female subjects of reproductive potential must agree to use a highly effective method of birth control, during the study and for 7 months following the last dose of study medication;
  • Male subjects must agree to use condoms during the study and for 6 months following the last dose of study medication. Disease specific inclusion criteria;
• Histological or cytologically confirmed adenocarcinoma of the pancreas that has not been previously treated in the metastatic setting.
• Initial diagnosis of metastatic disease (as per American Joint Committee on Cancer 8th Edition [AJCC 2017]) must have occurred ≤ 6 weeks prior to screening.
• Subject has one or more metastatic lesions measurable by computed tomography (CT) scan (or magnetic resonance imaging (MRI), if the subject is allergic to CT contrast media) according to RECIST Version 1.1 criteria.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening and within 7 days prior to randomisation. 
• Subject has adequate biological parameters as demonstrated by the following blood counts:
  • Absolute neutrophil count (ANC) ≥ 2000/mm^3 without the use of hemopoietic growth factors within the last 7 days prior to randomisation;
  • Platelet count ≥ 100,000/mm^3;
  • Haemoglobin (Hgb) ≥ 9 g/dL obtained ≤ 14 days prior to randomisation.
• Adequate hepatic function as evidenced by:
  • Serum total bilirubin ≤ 1.5x upper limit of normal (ULN) (biliary drainage is allowed for biliary obstruction); and
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5x ULN (≤ 5x ULN is acceptable if liver metastases are present).
• Adequate renal function with a creatinine clearance (CLCR) of > 30 mL/min. Actual body weight should be used for calculating CLCR using the Cockcroft-Gault Equation: CLCR (mL/min) = ((140–Age [years]) * (Weight [kg]/(Serum Creatinine [mg/dL]*72). Multiply the result by 0.85 if the subject is female. For subjects with a body mass index (BMI) > 30 kg/m^2, adjusted body weight should be used instead.
• Electrocardiogram (ECG) without any clinically significant findings (QT interval corrected by Fridericia’s formula (QTcF) ≤ 450 msec and no known arrhythmias) and per the investigator’s assessment.
• Adequate coagulation studies (obtained ≤ 14 days prior to randomisation) as demonstrated by prothrombin time and partial thromboplastin time within normal limits (≤ 1.5 x ULN). (Subjects on warfarin or other vitamin K antagonists should be discussed with the sponsor).
• Subject has no clinically significant abnormalities in urinalysis results (obtained within the last 7 days prior to randomisation), per the investigator’s assessment.
• Subjects infected with human immunodeficiency virus (HIV) are eligible if they meet all the following criteria:
  • CD4 count is ≥ 350 cells/uL, viral load is undetectable, and not taking prohibited cytochrome (CYP)-interacting medications;
  • Probable long-term survival with HIV if cancer were not present;
  • Stable on a highly active antiretroviral therapy (HAART) regimen for ≥ 4 weeks and willing to adhere to their HAART regimen with minimal overlapping toxicity and drug-drug interactions with the experimental agents in this study;
  • HIV is not multi-drug resistant;
  • Taking medication and/or receiving antiretroviral therapy that does not interact or have overlapping toxicities with the study medication.

Exclusion Criteria:

• Any other medical or social condition deemed by the investigator to be likely to interfere with a subject’s ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results.
• Unwilling or unable to comply with study procedures and/or study visits, including long-term follow-up for survival. 
• Prior treatment of pancreatic cancer in the metastatic setting with surgery, radiotherapy, chemotherapy or investigational therapy:
  • Palliative radiotherapy is permitted;
  • Placement of biliary stent/tube is permitted.
• 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.
• Subject has only localised advanced disease.
• Documented serum albumin Grade 1, malabsorption syndrome, ulcerative colitis, inflammatory bowel disease or partial bowel obstruction.
• History of any second malignancy in the last 2 years; subjects with prior history of in-situ cancer or basal or squamous cell skin cancer are eligible. Subjects with a history of other malignancies are eligible if they have been continuously disease free for at least 2 years prior to screening. Subjects who have a concurrent malignancy that is clinically stable and does not require tumour-directed treatment are eligible. 
• Known hypersensitivity to any of the components of irinotecan liposome injection, other liposomal products, or any components of 5-FU, LV or oxaliplatin.
• Known hypersensitivity to any of the components of nab-paclitaxel or gemcitabine.

Eligibility last updated 12/10/21. Questions regarding updates should be directed to the study team contact.