PRIMUS002: A study looking at two neo-adjuvant chemotherapy treatments for pancreatic cancer in patients whose cancer is able to be operated on
| ISRCTN | ISRCTN34129115 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN34129115 |
| EudraCT/CTIS number | 2016-004156-29 |
| Secondary identifying numbers | PRIMUS0022016 |
- Submission date
- 05/05/2017
- Registration date
- 05/05/2017
- Last edited
- 10/04/2024
- Recruitment status
- Stopped
- Overall study status
- Stopped
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year
Plain English summary of protocol
Contact information
Ms Sarah Bradley
Public
Public
University of Glasgow
Clinical Trials Unit, Level 0
Beatson West of Scotland Cancer Centre
1053 Great Western Road
Glasgow
G12 0YN
United Kingdom
| Phone | +44 (0)141 301 7540 |
|---|---|
| sarah.bradley@glasgow.ac.uk |
Study information
| Study design | Integrated interventional open-label non-randomized Phase II study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | 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 |
| Study acronym | PRIMUS 002 |
| Study objectives | That biomarker positive patients will respond better to FOLFOX-A treatment than biomarker negative patients in the neo-adjuvant setting. |
| Ethics approval(s) | Approved 14/08/2018, Approved 14/08/2018, NHS Lothian, Edinburgh Committee, Scotland A (NHS Lothian, Waverley Gate, 2 - 4 Waterloo Place, Edinburgh,, EH1 3EG, United Kingdom; +44 (0)131 465 5473; Manx.Neill@nhslothian.scot.nhs.uk), ref: 18/SS/0076 |
| Health condition(s) or problem(s) studied | Pancreatic cancer |
| Intervention | 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. Or: 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. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | FOLFOX-A (nab-paclitaxel, oxaliplatin, folinic acid, fluouracil), AG (nab-paclitaxel, gemcitabine) |
| Primary outcome measure | 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 study start date | 01/04/2017 |
| Completion date | 01/03/2022 |
| Reason abandoned (if study stopped) | Lack of funding/sponsorship |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Lower age limit | 16 Years |
| Upper age limit | 99 Years |
| Sex | Both |
| Target number of participants | 242 |
| Total final enrolment | 31 |
| Key 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 8.1.8.1) 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 |
| Key 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 |
| Date of first enrolment | 01/09/2018 |
| Date of final enrolment | 19/08/2021 |
Locations
Countries of recruitment
- England
- Scotland
- United Kingdom
Study participating centres
Beatson West of Scotland Cancer Centre
1053 Great Western Road
Glasgow
G12 0YN
United Kingdom
Glasgow
G12 0YN
United Kingdom
The Christie NHS Foundation Trust
550 Wilmslow Road
Manchester
M20 4BX
United Kingdom
Manchester
M20 4BX
United Kingdom
Western General Hospital
Crewe Road South
Edinburgh
EH4 2XU
United Kingdom
Edinburgh
EH4 2XU
United Kingdom
Royal Free Hospital
Pond Street
London
NW3 QG
United Kingdom
London
NW3 QG
United Kingdom
Sponsor information
NHS Greater Glasgow and Clyde
Hospital/treatment centre
Hospital/treatment centre
West Glasgow Ambulatory Care Hospital
Dalnair Street
Glasgow
Glasgow
G3 8SW
Scotland
United Kingdom
| Phone | +44 1412 321818 |
|---|---|
| Joanne.McGarry@ggc.scot.nhs.uk | |
"ROR" |
https://ror.org/05kdz4d87 |
Funders
Funder type
Charity
Cancer Research UK
Private sector organisation / Other non-profit organizations
Private sector organisation / Other non-profit organizations
- Alternative name(s)
- CR_UK, Cancer Research UK - London, CRUK
- Location
- United Kingdom
Celgene
No information available
Results and Publications
| Intention to publish date | 10/04/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| 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 Sarah Bradley (Sarah.Bradley@glasgow.ac.uk). |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
10/04/2024: The intention to publish date was changed from 01/03/2023 to 10/04/2025. Ethics approval details added.
24/11/2021: The study has been stopped due to funding withdrawal and following changes have been made to the trial record:
1. The recruitment end date has been changed from 01/09/2021 to 19/08/2021.
2. The total final enrolment number has been added.
09/12/2020: The following changes were made to the trial record:
1. Recruitment to this study is no longer paused.
2. Contact details updated.
3. The target number of participants was changed from 178 to 242.
4. Western General Hospital and Royal Free Hospital were added as trial participating centres.
09/04/2020: Due to current public health guidance, recruitment for this study has been paused.
19/11/2019: The following changes have been made:
1. The ethics approval information has been changed.
2. An additional public contact has been added.
05/04/2019: Cancer Research UK lay summary link added to plain English summary field.
05/03/2019: Internal review.
07/06/2018: Recruitment start date was changed from 01/12/2017 to 01/09/2018
06/06/2018: Internal review.
14/05/2018: Internal review.
16/01/2018: Internal review.
11/08/2017: Internal review.
06/06/2017: Internal review.
