PRIMUS 001: An adaptive phase II study of FOLFOX-A (FOLFOX and nab-paclitaxel) versus AG (nab-paclitaxel and gemcitabine) in patients with metastatic pancreatic cancer, with integrated biomarker evaluation
Metastatic pancreatic cancer
Patients will call the CTU to randomise the patients and they will be randomised on a 1:1 basis with 50% receiving AG and 50% FOLFOX-A. Minimisation will be used to allocate patients between the treatment arms, the following factors will be used: treatment centre, whether or not the patient has liver metastasis, whether the primary tumour is in the head or the tail of the pancreas and the patients baseline CA19.9. FOLFOX-A (nab-paclitaxel 150mg/m2 IV over 30 minutes, day 1 (administered first), Oxaliplatin: 85mg/m2, IV over 2 hours, day 1, Folinic acid: 350 mg flat dose or 400mg/m2, IV over 2 hours, day 1 (as per standard of care for folinic acid dosing), 5-FU infusion:1200mg/m2/day, as a continuous IV infusion over 2 days, day 1 and day 2 (for a total dose of 2400mg/m2 over 46 hours.) OR AG (nab-paclitaxel: 125 mg/m2 IV over 30 minutes, day 1,8, and 15 (administered first and Gemcitabine 1000 mg/m2 IV over 30 mins on days 1, 8, and 15 (immediately following nab-paclitaxel). When the patient progressed on CT scan treatment will stop and the end of treatment visit will take place with 28 days of the last treatment. At this visit any con meds will be reviewed, physical exam (weight, BP, pulse), ECOG, blood count and biochemistry, assessment of adverse events, CA19.9 and quality of life. After that patients will be followed up every 3 months for the first year post randomisation, 18 months after randomisation, 24 months and then annually for up to 5 years. At these visits con meds, including any new cancer treatments will be recorded, ECOG, CA19.9, quality of life assessments and survival status will be recorded.
1. Patient has been enrolled in the Precision Panc Master Protocol and their tissue has been deemed suitable for NGS analysis 2. Patient has provided signed information consent for the PRIMUS 001 study 3. Age 16 years and over 4. Histologically-confirmed metastatic pancreatic ductal adenocarcinoma and its varients, with measurable metastatic lesion(s) according to RECIST 1.1. 5. Eastern Cooperative Oncology Group (ECOG) 0-1 with life expectation of no less than 12 weeks. 6. 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. 7. Adequate liver/bone marrow function as defined by: 7.1. Neutrophils (ANC) ≥ 1.5 x 109/l 7.2. Platelets ≥ 100 x 109/l 7.3. Haemoglobin ≥ 9.0 g/dL 7.4. WBC ≥ 3 x 109/l 7.5. Total bilirubin ≤ 1.5 x institutional ULN unless bilirubin rise is due to Gilbert’s syndrome 7.6. Aspartate transaminase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN (and <5 ULN in the presence of liver metastases) 7.7. Estimated creatinine clearance ≥ 60 mL/min (as calculated by Cockcroft and Gault or Wright formula or measured by EDTA clearance) 8. Negative serum 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 9. Woman of child bearing potential, and men with female partners of child bearing potential, must agree to use adequate contraceptive measures (see section 8.1.8.1) for the duration of the study and for up to 6 months after the completion of study treatment. 10. Compliant, and can be followed up regularly The following additional inclusion criteria is ONLY required if recommended by the independent Data Monitoring Comm
Current exclusion criteria as of 12/03/2024: 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 metastatsis or mental illness 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 (DPD) deficiency 10. Pregnant of 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 3 years (other than treated squamous/basal cell skin cancer, treated early-stage cervical cancer or treated/biochemically-stable, organ-confined prostate cancer) 19. Any patient with severe diarrhoea (defined as ≥grade 3 diarrhoea despite maximum supportive measures and exclusion of underlying infection _____ Previous 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