PRIMUS 002: An umbrella phase II study examining two neo-adjuvant regimens (FOLFOX-A and AG) in resectable and borderline resectable Pancreatic Ductal AdenoCarcinoma (PDAC), focusing on biomarker and liquid biopsy development
That biomarker positive patients will respond better to FOLFOX-A treatment than biomarker negative patients in the neo-adjuvant setting.
Not provided at time of registration
Integrated interventional open label non randomised phase II study
Primary study design
Secondary study design
Non randomised study
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Patients will be registered according to their performance status and age (younger patients with better performance status will be registered to receive FOLFOX-A, with older patients with worse performance status will be registered to receive AG)
FOLFOX A arm (14-day cycle)
1. nab-paclitaxel: 150mg/m2 IV over 30 minutes, day 1 (administered first).
2. Oxaliplatin: 85mg/m2, IV over 2 hours, day 1.
3. Folinic acid: 350 mg flat dose or 400mg/m2, IV over 2 hours, day 1 (as per standard of care for folinic acid dosing. Please inform CRUK CTU if not using 350mg flat dose).
4. Fluouracil 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.)
Patients will receive 6 cycles in total.
Nab-Paclitaxel + Gemcitabine (AG) arm (28-day cycle)
1. nab-paclitaxel: 125 mg/m2 IV over 30 minutes, day 1,8,15 (administered first).
2. Gemcitabine 1000 mg/m2 on days 1, 8, and 15 (immediately following nab-paclitaxel).
Patients will receive 3 cycles in total.
Primary outcome measures
1. Time to progression following FOLFOX-A treatment is assessed through CT scans at baseline, prior to radiotherapy and prior to surgery. Further scans will be performed as per standard of care to progression.
2. Efficacy of proposed biomarkers in predicting disease progression rates in FOLFOX-A arm. Tissue samples will be collected from the patients at baseline (under the Precision Panc Master Protocol), prior to radiotherapy and at surgery/progression.
Secondary outcome measures
1. Translational research assessment of cloncal evolution and acquired resistance mechanisms due to treatment,
Response based on RECIST 1.1 post neo-adjuvant chemotherapy. The patient will have a CT scan at baseline, prior to radiotherapy and prior to surgery. Further scans will be performed as per standard of care to progression.
2. CAP tumour regression grade post surgery, this will be assessed by MDT after surgery
3. R0 rate post surgery, this will be assessed by MDT after surgery
4. Overall survival, this will be assessed at every chemotherapy visit, radiotherapy planning, radiotherapy, surgery and at every follow up visit (6, 9, 12, 18, 24, 36, 48, 60 months post registration)
5. Disease free survival, this will be assessed at every chemotherapy visit, radiotherapy planning, radiotherapy, surgery and at every follow up visit (6, 9, 12, 18, 24, 36, 48, 60 months post registration)
6. Safety and tolerability as assessed by NCI CTC 4.03, this will be assessed at every chemotherapy visit, radiotherapy planning, radiotherapy, surgery and at every follow up visit (6, 9, 12, 18, 24, 36, 48, 60 months post registration)
7. Neurotoxicity as assessed by GOG NTx4, this will be assessed montlhy while on chemotherapy, prior to surgery and at follow-up visits
8. Quality of life as assessed by EORTC QLQ-C30 version 3 and the pancreatic-specific QLQ-PAN26 QOL module, this will be assessed montlhy while on chemotherapy, prior to surgery and at follow-up visits
Overall trial start date
Overall trial end date
Participant inclusion criteria
1. Patient has provided written informed consent and is registered to the PRECISION PANC master protocol
2. Signed informed consent given for PRIMUS 002 study
3. Age ≥ 16 years
4. Resectable or borderline resectable pancreatic cancer as defined by RECIST v1.1 criteria following discussion at the MDT
5. Measurable Disease as per RECIST 1.1
6. Histological or cytologically proven pancreatic ductal adenocarcinome (including variants)
7. Able to undergo biliary drainage using a covered or partially covered self-expanding metal stent if jaundiced
8. ECOG performance status 0 and 1
9. Adequate liver/bone marrow function as defined by:
9.1. Neutrophils ≥ 1.5 x 109/l
9.2. Platelets ≥ 100 x 109/l
9.3. Haemoglobin ≥ 9.0g/dL
9.4. WBC ≥ 3 x 109/l
9.5. Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) unless bilirubin rise is due to Gilbert’s syndrome
9.6. Aspartate transaminase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN (and <5 x ULN in the presence of liver metastases)
9.7. Estimated creatinine clearance > 60 mL/min
10. 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
11. Woman of child bearing potential, and men with female partners of child bearing potential, must agree to use adequate contraceptive measures (see section 126.96.36.199) for the duration of the study and for up to 6 months after the completion of study treatment.
12. Able to comply with protocol requirements and deemed fit for surgical resection, chemotherapy and radiotherapy
Target number of participants
Participant exclusion criteria
1. Unable to obtain sufficient tissue for NGS analysis
2. Distant metastatic disease
3. History of previous or concurrent malignancy diagnosis (except curatively treated basil cell carcinoma of skin or carcinoma in situ of cervix)
4. Prior chemotherapy or chemoradiotherapy (exceptions may be given case by case by the Chief Investigator (CI), such as methotrexate for rheumatoid arthritis)
5. Known hypersensitivity for any component of any study drug
6. Active infection including Herpes Zoster and chickenpox
7. Uncontrolled congestive heart failure (CHF), or history of myocardial ischemia (MI), unstable angina, stroke, or transient ischemia within previous 6 months.
8. Serious medical or psychological condition precluding neoadjuvant treatment and surgical resection
9. New York Heart Association Classification Grade III or IV
10. Uncontrolled angina/ischaemic heart disease
11. Major surgery within 28 days prior to trial entry
12. Any patients receiving treatment with brivudin, sorivudin and analogues
13. Any patient with severe diarrhoea.
14. Patients with known malabsorption
15. Patients with known or suspected DPD (dihydropyrimidine dehydrogenase) deficiency.
16. Grade ≥ 2 peripheral neuropathy
17. Administration of any investigational drug within 28 days or 5 half-lives, whichever is longer, prior to receiving the first dose of trial treatment
Recruitment start date
Recruitment end date
Countries of recruitment
Trial participating centre
Beatson West of Scotland Cancer Centre
1053 Great Western Road
Trial participating centre
The Christie NHS Foundation Trust
550 Wilmslow Road
NHS Greater Glasgow and Clyde
West Glasgow Ambulatory Care Hospital
+44 1412 321818
Cancer Research UK
Funding Body Type
private sector organisation
Funding Body Subtype
Funding Body Type
Funding Body Subtype
Results and Publications
Publication and dissemination plan
Planned publication in a high-impact peer reviewed journal.
IPD Sharing plan:
The datasets generated during and/or analysed during the current study are/will be available upon request from Judith Dixon (Judith.Dixon@glasgow.ac.uk)
Intention to publish date
Participant level data
Available on request
Results - basic reporting