Condition category
Cancer
Date applied
05/05/2017
Date assigned
05/05/2017
Last edited
07/06/2018
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Lay summary under review with external organisation

Trial website

Contact information

Type

Public

Primary contact

Ms Judith Dixon-Hughes

ORCID ID

http://orcid.org/0000-0002-5596-4400

Contact details

CRUK CTU Glasgow
Level 0
Beatson WoSCC
1053 Great Western Road
Glasgow
G12 0YN
United Kingdom
+44 1413 017540
judith.dixon@glasgow.ac.uk

Additional identifiers

EudraCT number

2016-004156-29

ClinicalTrials.gov number

Protocol/serial number

PRIMUS0022016

Study information

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

Acronym

PRIMUS 002

Study hypothesis

That biomarker positive patients will respond better to FOLFOX-A treatment than biomarker negative patients in the neo-adjuvant setting.

Ethics approval

Not provided at time of registration

Study design

Integrated interventional open label non randomised phase II study

Primary study design

Interventional

Secondary study design

Non randomised study

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

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

Phase

Phase II

Drug names

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 trial start date

01/04/2017

Overall trial end date

01/03/2022

Reason abandoned (if study stopped)

Eligibility

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 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

Participant type

Patient

Age group

Mixed

Gender

Both

Target number of participants

178

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

01/09/2018

Recruitment end date

01/09/2021

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Beatson West of Scotland Cancer Centre
1053 Great Western Road
Glasgow
G12 0YN
United Kingdom

Trial participating centre

The Christie NHS Foundation Trust
550 Wilmslow Road
Mancheaster
M20 4BX
United Kingdom

Sponsor information

Organisation

NHS Greater Glasgow and Clyde

Sponsor details

West Glasgow Ambulatory Care Hospital
Dalnair Street
Glasgow
Glasgow
G3 8SW
United Kingdom
+44 1412 321818
Joanne.McGarry@ggc.scot.nhs.uk

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Charity

Funder name

Cancer Research UK

Alternative name(s)

CRUK

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Funder name

Celgene

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

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

01/03/2023

Participant level data

Available on request

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

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.