Condition category
Cancer
Date applied
30/05/2017
Date assigned
31/05/2017
Last edited
16/10/2017
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

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

2016-004155-67

ClinicalTrials.gov number

Protocol/serial number

PRIMUS0012016

Study information

Scientific title

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

Acronym

PRIMUS 001

Study hypothesis

That FOLFOX-A will increase progression free survival in metastatic pancreatic cancer patients over AG

Ethics approval

Not provided at time of registration

Study design

Multi-centre randomised open label two arm phase II trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

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

Metastatic pancreatic cancer

Intervention

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.

Intervention type

Drug

Phase

Phase II

Drug names

Primary outcome measures

Progression free survival as measured by IV contrast enhanced CT scan every 8 weeks from the date of randomisation to progression or death (from any cause), whichever occurs first.

Secondary outcome measures

1. Objective response rate based on RECIST v1.1 will be measured by contrast enchanged CT scan every 8 weeks until disease progression
2. Overall survival will be recorded at each study visit up to 60 months post randomisation
3. Safety and tolerability will be assessed using NCI-CTCAE v4. Adverse events will be collected at each treatment visit and the end of treatment visit.
4. Quality of life will be assessed using EORTC QLQ-C30, QLQ PAN26, ED-5D-5L monthly while on treatment and then at each follow up visit
5. Peripheral neuropathy will be assessed by the GOG-NTX4 questionnaire monthly while on treatment and then at each follow up visit
6. Health Economics: Resource use will be assessed by the EQ-5d-5L monthly while on treatment and then at each follow up visit. Information will also be collected regarding any inpatients stays in hospital during the course of the study

Overall trial start date

01/04/2017

Overall trial end date

01/01/2023

Reason abandoned

Eligibility

Participant inclusion criteria

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 Committee after interim review of study data (sites will have been informed by the CRUK CTU if this is the case):
11. Patient must be biomarker positive as fed back after central Precision-PANC diagnostic testing

Participant type

Patient

Age group

Mixed

Gender

Both

Target number of participants

500

Participant 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 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 5 years (other than treated squamous/basal cell skin cancer, treated early-stage cervical cancer or treated/bio
18. Chemically-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

Recruitment start date

01/09/2017

Recruitment end date

30/06/2021

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Beatson West of Scotland Cancer Centre
1053 Great Western Road
Glasgow
G20 9JG
United Kingdom

Trial participating centre

Addenbrooke's Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom

Trial participating centre

Bristol Haematology and Oncology Centre
Horfield Road
Bristol
BS2 8ED
United Kingdom

Trial participating centre

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

Trial participating centre

Guy's Hospital
Great Maze Pond
London
SE1 9RT
United Kingdom

Trial participating centre

Imperial College Healthcare NHS Trust
London
W12 0HS
United Kingdom

Trial participating centre

Ninewells Hospital and Medical School
Dundee
DD1 9SY
United Kingdom

Trial participating centre

Northern Ireland Cancer Centre
Belfast City Hospital 10 Jubilee Road
Belfast
BT9 7AB
United Kingdom

Trial participating centre

Royal Marsden Hospital
Downs Road
Sutton
SM2 5PT
United Kingdom

Trial participating centre

St George's Hospital
Blackshaw Road
London
SW17 0QT
United Kingdom

Trial participating centre

University College Hospital
235 Euston Road Bloomsbury
London
NW1 2PG
United Kingdom

Trial participating centre

University Hospital Southampton
Tremona Road
Southampton
So16 6YD
United Kingdom

Sponsor information

Organisation

NHS Greater Glasgow and Clyde

Sponsor details

West Glasgow Ambulatory Care Hospital
Dalnair Street
Glasgow
G3 8SJ
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)

Celgene Corporation

Funding Body Type

private sector organisation

Funding Body Subtype

corporate

Location

United States of America

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer reviewed journal

IPD sharing statement:
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

01/12/2023

Participant level data

Available on request

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

16/10/2017: Internal review. 11/08/2017: Internal review. 06/06/2017: Internal review.