PRIMUS 001: A Study Looking at Two Different Chemotherapy Regimens in Patients With Metastatic Pancreatic Cancer

Neoplasms Pancreatic Clinical Trial

Official 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04151277
• Other study ID #: PRIMUS0012016
• Status: Recruiting
• Phase: Phase 2
• Start date: November 28, 2017
• Est. completion date: January 31, 2026

Study information

• Verified date: February 2024
• Source: University of Glasgow
• Contact: Sarah Bradley
• Phone: 01413017540
• Email: sarah.bradley[@]glasgow.ac.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is comparing two combinations of chemotherapy treatments in patients with metastatic pancreatic cancer. Half the participants will receive FOLFOX-A and the other half will receive AG. Treatment will continue until progression or patient/clinican decision or intolerable toxicity.

Description:

PRIMUS 001 is a multicentre, randomised, open label, two arm, phase II interventional trial with pre-clinical and translational work including in-depth molecular profiling and biomarker discovery/development. The primary objective is to look at the efficacy of FOLFOX-A compared to AG in all comers and in a biomarker positive group using progression free survival.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: January 31, 2026
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

Inclusion Criteria:

1. Patient has been enrolled in the Precision-Panc Master Protocol

2. Patient has provided signed information consent for the PRIMUS 001 study

3. Age = 16 years

4. Histologically-confirmed pancreatic ductal adenocarcinoma and its varients

5. Measurable metastatic disease according to RECIST V1.1

6. Eastern Cooperative Oncology Group (ECOG) 0-1 with life expectation of no less than 12 weeks

7. 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

8. Adequate liver/bone marrow function as defined by:

1. Neutrophils (ANC) = 1.5 x 109/l

2. Platelets = 100 x 109/l

3. Haemoglobin = 9.0 g/dL

4. White Blood Cells (WBC) = 3 x 109/l

5. Total bilirubin = 1.5 x institutional ULN unless bilirubin rise is due to Gilbert's syndrome

6. Aspartate transaminase (AST) and alanine aminotransferase (ALT) = 2.5 x ULN ( <5 ULN in the presence of liver metastases)

7. Estimated creatinine clearance = 60 mL/min (as calculated by Cockcroft and Gault or Wright formula or measured by EDTA clearance) 9. Negative serum or urine 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 10. Woman of child bearing potential, and men with female partners of child bearing potential, must agree to use adequate contraceptive measures (see s section 8.1.8.1) for the duration of the study and for up to 6 months after the completion of study treatment. 11. 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 Cancer Research UK (CRUK) Clinical Trials Unit (CTU) if this is the case) 12. Patient must be biomarker positive as fed back after central Precision-Panc diagnostic testing

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 metastasis

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 dehydrogenase (DPD) deficiency

10. Pregnant or 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/biochemically-stable organ-confined prostate cancer)

18. Any patient with severe diarrhoea (defined as =grade 3 diarrhoea despite maximum supportive measures and exclusion of underlying infection)

Related Conditions & MeSH terms

• Neoplasms Pancreatic

Intervention

Drug:
• FOLFOX-A
Patients will recieve nab-paclitaxel, oxaliplatin, Folinic Acid and 5-FU in a 14 day cycle
• Gemcitabe and Abraxane
Patients will receive gemcitabine and nab-paclitaxel 3 weeks out of 4
• G-CSF
Patients in the FOLFOX-A arm will also receive daily G-CSF as primary prophylaxis for all cycles. This will be given as per local site policy for 14 day chemotherapy regimens

Locations

Country	Name	City	State
United Kingdom	Aberdeen Royal Infirmary	Aberdeen
United Kingdom	Northern Ireland Cancer Centre	Belfast
United Kingdom	Queen Elizabeth Hospital	Birmingham
United Kingdom	Royal Bournemouth Hospital	Bournemouth
United Kingdom	Bristol Oncology Centre	Bristol
United Kingdom	Addenbrooke's Hospital	Cambridge
United Kingdom	Castle Hill Hospital	Cottingham
United Kingdom	Ninewells Hospital	Dundee
United Kingdom	Western General	Edinburgh
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	Huddersfield Royal Infirmary	Huddersfield
United Kingdom	Raigmore Hospital	Inverness
United Kingdom	St James's University Hospital	Leeds
United Kingdom	The Clatterbridge Cancer Centre	Liverpool
United Kingdom	Guy's Hospital	London
United Kingdom	Imperial College Healthcare Trust	London
United Kingdom	Royal Free London Hospital	London
United Kingdom	Royal Marsden Hospital	London
United Kingdom	St Bart's Hospital	London
United Kingdom	St George's Hospital	London
United Kingdom	University College London Hospital	London
United Kingdom	The Christie, Manchester	Manchester
United Kingdom	Milton Keynes General Hospital	Milton Keynes
United Kingdom	Freeman Hospital	Newcastle
United Kingdom	Nottingham University Hospital	Nottingham
United Kingdom	Churchill Hospital	Oxford
United Kingdom	Poole Hospital	Poole
United Kingdom	Weston Park	Sheffield
United Kingdom	University of Southampton Hospital	Southampton
United Kingdom	Singleton Hospital	Swansea

Sponsors (3)

Lead Sponsor	Collaborator
Judith Dixon-Hughes	NHS Greater Glasgow and Clyde, University of Glasgow

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival	Progression free survival as measured froim the date of randomisation to progression or death (from any cause)	At time of progression (estimated to be between 5 and 7.5 months)
Secondary	Ojective Response Rate	Based on RECIST version 1.1	Measured every 8 weeks by CT scan (most patients will received 3-4 CT scans over 24-32 weeks))
Secondary	Overall Survival	Survival will be measured from the date of randomisation and include all caused of death	From date of randomisation until date of death from any cause. Most patients with metastatic pancreatic cancer will die within 6-9 months from diagnosis
Secondary	Safety and Tolerability of FOLFOX-A treatment	Using NCI-CTCAE version 4.03	At every chemotherapy visit (every 2 weeks) - and at end of treatment visit (within 30 days of completing chemotherapy). Chemotherapy will continue until progression (estimated at between 5-7.5 months)
Secondary	Safety and Tolerability of AG treatment	Using NCI-CTCAE version 4.03	At every chemotherapy visit (3 weeks out of every 4) - and at end of treatment visit (within 30 days of completing chemotherapy). Chemotherapy will continue until progression (estimated at between 5-7.5 months)
Secondary	Quality of Life (EORTC QLQ-C30)	patients will complete the EORTC QLQ-C30 questionnaire at clinic	Every 8 weeks while on treatment, at end of treatment visit, which will take place within 30 days of completing treatment, and at follow-up visits (6, 9, 12, 18, 24, 36, 48 and 60 months post randomisation).
Secondary	Peripheral Neuropathy	Measured by GOG-NTX4	Every 4 weeks while on treatment, at end of treatment visit and at follow-up visits (6, 9, 12, 18, 24, 36, 48 and 60 months post randomisation).
Secondary	Health Economics as defined to hospital resource use i.e how many nights the patient has spent in hospital and how may times they have attended hospital since the last time they were seen	Resource use will be assessed during the course of the study	At each study visit. Patient will be followed up for up to 5 years post randomistation (6, 9, 12, 18, 24, 36, 48 and 60 months post randomisation).
Secondary	Biomarker Discovery and Development	This will be ongoing as part of the study. This will use trial material but will be extrinsic to the trials outcomes. The biomarker will be specificed and locked down before the first interim analysis that is biomarker dependent	Ongoing during study. Recruitment will take 46 months and patients will be followed-up for up to 5 years post randomisation
Secondary	Quality of Life (EORTC QLQ-PAN26)	patients will complete the EORTC QLQ-PAN26 questionnaire at clinic	Every 8 weeks while on treatment, at end of treatment visit, which will take place within 30 days of completing treatment, and at follow-up visits (6, 9, 12, 18, 24, 36, 48 and 60 months post randomisation).
Secondary	Quality of Life (EQ-5D-5L)	patients will complete the EQ-5D-5L questionnaire at clinic	Every 8 weeks while on treatment, at end of treatment visit, which will take place within 30 days of completing treatment, and at follow-up visits (6, 9, 12, 18, 24, 36, 48 and 60 months post randomisation).