Overview

This study is comparing two combinations of chemotherapy treatments in patients with metastatic pancreatic cancer. Half the participants will receive FOLFOX-A and the other half will receive AG. Treatment will continue until progression or patient/clinican decision or intolerable toxicity.

Eligibility

Inclusion Criteria:

1. Patient has been enrolled in the Precision-Panc Master Protocol
2. Patient has provided signed information consent for the PRIMUS 001 study
3. Age ≥ 16 years
4. Histologically-confirmed pancreatic ductal adenocarcinoma and its varients
5. Measurable metastatic disease according to RECIST V1.1
6. Eastern Cooperative Oncology Group (ECOG) 0-1 with life expectation of no less than 12 weeks
7. Patients must have received no previous chemotherapy or investigational therapy for the treatment of metastatic disease. Prior treatment with a fluoropyrimidine and/or gemcitabine administered in the adjuvant setting is allowed, provided at least 6 months have elapsed since completion of the last dose and no ongoing toxicities are present
8. Adequate liver/bone marrow function as defined by:
   1. Neutrophils (ANC) ≥ 1.5 x 109/l
   2. Platelets ≥ 100 x 109/l
   3. Haemoglobin ≥ 9.0 g/dL
   4. White Blood Cells (WBC) ≥ 3 x 109/l
   5. Total bilirubin ≤ 1.5 x institutional ULN unless bilirubin rise is due to Gilbert's syndrome
   6. Aspartate transaminase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN ( <5 ULN in the presence of liver metastases)
   7. Estimated creatinine clearance ≥ 60 mL/min (as calculated by Cockcroft and Gault or Wright formula or measured by EDTA clearance) 9. Negative serum or urine Human Chorionic Gonadotropin (HCG) test for females with child bearing potential. Postmenopausal women must have been amenorrhoeic for at least 12 months to be considered of non-childbearing potential 10. Woman of child bearing potential, and men with female partners of child bearing potential, must agree to use adequate contraceptive measures (see s section 8.1.8.1) for the duration of the study and for up to 6 months after the completion of study treatment. 11. Compliant, and can be followed up regularly

        The following additional inclusion criteria is ONLY required if recommended by the
        independent Data Monitoring Committee after interim review of study data (sites will have
        been informed by the Cancer Research UK (CRUK) Clinical Trials Unit (CTU) if this is the
        case) 12. Patient must be biomarker positive as fed back after central Precision-Panc
        diagnostic testing
        Exclusion Criteria:
          1. Prior treatment with nab-paclitaxel or oxaliplatin
          2. Prior chemotherapy for metastatic pancreatic cancer
          3. Known hypersensitivity for any component of any study drug
          4. Active infection including Herpes Zoster and chickenpox
          5. Current neuropathy ≥ grade 2
          6. Uncontrolled brain metastasis
          7. Uncontrolled congestive heart failure (CHF), or history of myocardial ischemia (MI),
             unstable angina, stroke, or transient ischemia within previous 6 months
          8. Uncontrolled serious contraindicated medical condition or illness
          9. Known or suspected dihydropyrimidine dehydrogenase (DPD) deficiency
         10. Pregnant or breastfeeding
         11. History of physical or psychiatric disorder that would prevent informed consent and
             compliance with protocol
         12. Administration of any investigational drug within 28 days or 5 half-lives, whichever
             is longer, of receiving the first dose of trial treatment
         13. Any systemic anti-cancer therapy or major surgery within 28 days of randomisation
         14. Any minor surgery or radiotherapy within 7 days of randomisation
         15. Any psychological, familial, sociological or geographical consideration potentially
             hampering compliance with the trial protocol and follow up schedule
         16. Any patients receiving treatment with brivudin, sorivudin and analogues
         17. History of another malignancy in the last 5 years (other than treated squamous/basal
             cell skin cancer, treated early-stage cervical cancer or treated/biochemically-stable
             organ-confined prostate cancer)
         18. Any patient with severe diarrhoea (defined as ≥grade 3 diarrhoea despite maximum
             supportive measures and exclusion of underlying infection)