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

February 7, 2024 updated by: Judith Dixon-Hughes

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Estimated)

500

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United Kingdom
      • Aberdeen, United Kingdom
        • Recruiting
        • Aberdeen Royal Infirmary
        • Principal Investigator:
          • Ishtiaq Zubairi
        • Contact:
      • Belfast, United Kingdom
      • Birmingham, United Kingdom
        • Recruiting
        • Queen Elizabeth Hospital
        • Contact:
        • Principal Investigator:
          • Yuk Ting Ma
      • Bournemouth, United Kingdom
        • Recruiting
        • Royal Bournemouth Hospital
        • Contact:
        • Principal Investigator:
          • Tamas Hickish
      • Bristol, United Kingdom
      • Cambridge, United Kingdom
      • Cottingham, United Kingdom
      • Dundee, United Kingdom
        • Recruiting
        • Ninewells Hospital
        • Principal Investigator:
          • Asa Dahle Smith
        • Contact:
      • Edinburgh, United Kingdom
        • Recruiting
        • Western General
        • Contact:
          • Olga Demyanov
        • Principal Investigator:
          • Alan Christie
      • Glasgow, United Kingdom
        • Recruiting
        • Beatson West of Scotland Cancer Centre
        • Contact:
        • Principal Investigator:
          • Janet Graham
      • Huddersfield, United Kingdom, HD3 3EA
        • Recruiting
        • Huddersfield Royal Infirmary
        • Contact:
        • Principal Investigator:
          • Emma Rathbone
      • Inverness, United Kingdom
        • Recruiting
        • Raigmore Hospital
        • Principal Investigator:
          • Walter Mmeka
        • Contact:
          • Laura McLennan
      • Leeds, United Kingdom
        • Recruiting
        • St James's University Hospital
        • Contact:
        • Principal Investigator:
          • Fiona Collinson
      • Liverpool, United Kingdom, CH63 4JY
        • Recruiting
        • The Clatterbridge Cancer Centre
        • Contact:
        • Principal Investigator:
          • Daniel Palmer
      • London, United Kingdom
        • Recruiting
        • Royal Marsden Hospital
        • Contact:
        • Principal Investigator:
          • Naureen Starling
      • London, United Kingdom
        • Recruiting
        • University College London Hospital
        • Contact:
        • Principal Investigator:
          • Daniel Hochhauser
      • London, United Kingdom
        • Recruiting
        • Guy's Hospital
        • Contact:
          • Christina Armoogum
        • Principal Investigator:
          • Debashis Sarker
      • London, United Kingdom
        • Recruiting
        • Imperial College Healthcare Trust
        • Principal Investigator:
          • Harpreet Wasan
        • Contact:
      • London, United Kingdom
        • Recruiting
        • Royal Free London Hospital
        • Contact:
        • Principal Investigator:
          • Roopinder Gillmore
      • London, United Kingdom
        • Recruiting
        • St Bart's Hospital
        • Principal Investigator:
          • David Propper
        • Contact:
      • London, United Kingdom
      • Manchester, United Kingdom
      • Milton Keynes, United Kingdom
        • Recruiting
        • Milton Keynes General Hospital
        • Contact:
        • Principal Investigator:
          • Wasiru Saka
      • Newcastle, United Kingdom
        • Recruiting
        • Freeman Hospital
        • Contact:
        • Principal Investigator:
          • Jane Margetts
      • Nottingham, United Kingdom
        • Recruiting
        • Nottingham University Hospital
        • Principal Investigator:
          • Arora Arvind
        • Contact:
      • Oxford, United Kingdom
      • Poole, United Kingdom
      • Sheffield, United Kingdom
        • Recruiting
        • Weston Park
        • Principal Investigator:
          • Jonathan Wadsley
        • Contact:
      • Southampton, United Kingdom
        • Recruiting
        • University of Southampton Hospital
        • Principal Investigator:
          • Andrew Bateman
        • Contact:
      • Swansea, United Kingdom

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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, IV over 2 hours, day 1
  • 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 48 hours as per standard practice))
Drug: FOLFOX-A
Patients will recieve nab-paclitaxel, oxaliplatin, Folinic Acid and 5-FU in a 14 day cycle
Drug: 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
Active Comparator: Abraxane and Gemcitabine
  • nab-paclitaxel: 125 mg/m2 IV over 30 minutes, day 1, 8, and 15 (administered first)
  • Gemcitabine 1000 mg/m2 IV over 30 minutes on days 1, 8, and 15 (immediately following nab-paclitaxel)
Drug: Gemcitabe and Abraxane
Patients will receive gemcitabine and nab-paclitaxel 3 weeks out of 4

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival
Time Frame: At time of progression (estimated to be between 5 and 7.5 months)
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ojective Response Rate
Time Frame: Measured every 8 weeks by CT scan (most patients will received 3-4 CT scans over 24-32 weeks))
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))
Overall Survival
Time Frame: 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
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
Safety and Tolerability of FOLFOX-A treatment
Time Frame: 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)
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)
Safety and Tolerability of AG treatment
Time Frame: 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)
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)
Quality of Life (EORTC QLQ-C30)
Time Frame: 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).
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).
Peripheral Neuropathy
Time Frame: 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).
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).
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
Time Frame: 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).
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).
Biomarker Discovery and Development
Time Frame: Ongoing during study. Recruitment will take 46 months and patients will be followed-up for up to 5 years post randomisation
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
Quality of Life (EORTC QLQ-PAN26)
Time Frame: 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).
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).
Quality of Life (EQ-5D-5L)
Time Frame: 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).
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).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Judith Dixon-Hughes

Collaborators

NHS Greater Glasgow and Clyde
University of Glasgow

Investigators

  • Principal Investigator: Janet Graham, NHS Greater Glasgow and Clyde

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 28, 2017

Primary Completion (Estimated)

December 31, 2025

Study Completion (Estimated)

January 31, 2026

Study Registration Dates

First Submitted

October 25, 2019

First Submitted That Met QC Criteria

November 1, 2019

First Posted (Actual)

November 5, 2019

Study Record Updates

Last Update Posted (Actual)

February 8, 2024

Last Update Submitted That Met QC Criteria

February 7, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PRIMUS0012016

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

At the end of the study, once the study report has been written and published, the anonymised clinical data will be available via request to Trial Management Group

IPD Sharing Time Frame

After publication of study

IPD Sharing Access Criteria

On Request to Trial Management Group

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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