Clinical trial NCT04151277: PRIMUS 001: A Study Looking at Two Different Chemotherapy Regimens in Patients With Metastatic Pancreatic Cancer
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Neoplasms Pancreatic
Lead sponsor: University of Glasgow
Sponsor class: OTHER
Collaborators: name: NHS Greater Glasgow and Clyde
name: University of Glasgow
First posted: 2019-11-05
Enrollment: 500
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients will be randomised to each of the treatments 1:1
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Progression Free Survival
timeFrame: At time of progression (estimated to be between 5 and 7.5 months)
Secondary outcomes:
measure: Ojective Response Rate
timeFrame: Measured every 8 weeks by CT scan (most patients will received 3-4 CT scans over 24-32 weeks))
measure: Overall Survival
timeFrame: 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
measure: Safety and Tolerability of FOLFOX-A treatment
timeFrame: 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)
measure: Safety and Tolerability of AG treatment
timeFrame: 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)
measure: Quality of Life (EORTC QLQ-C30)
timeFrame: 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).
measure: Peripheral Neuropathy
timeFrame: 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).
measure: 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
timeFrame: 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).
measure: Biomarker Discovery and Development
timeFrame: Ongoing during study. Recruitment will take 46 months and patients will be followed-up for up to 5 years post randomisation
measure: Quality of Life (EORTC QLQ-PAN26)
timeFrame: 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).
measure: Quality of Life (EQ-5D-5L)
timeFrame: 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).
Other outcomes:
Locations:
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
city: Belfast
country: United Kingdom
facility: Northern Ireland Cancer Centre
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth Hospital
city: Bristol
country: United Kingdom
facility: Bristol Oncology Centre
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
city: Cottingham
country: United Kingdom
facility: Castle Hill Hospital
city: Dundee
country: United Kingdom
facility: Ninewells Hospital
city: Edinburgh
country: United Kingdom
facility: Western General
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
city: Huddersfield
country: United Kingdom
facility: Huddersfield Royal Infirmary
city: Inverness
country: United Kingdom
facility: Raigmore Hospital
city: Leeds
country: United Kingdom
facility: St James's University Hospital
city: Liverpool
country: United Kingdom
facility: The Clatterbridge Cancer Centre
city: London
country: United Kingdom
facility: Guy's Hospital
city: London
country: United Kingdom
facility: Imperial College Healthcare Trust
city: London
country: United Kingdom
facility: Royal Free London Hospital
city: London
country: United Kingdom
facility: Royal Marsden Hospital
city: London
country: United Kingdom
facility: St Bart's Hospital
city: London
country: United Kingdom
facility: St George's Hospital
city: London
country: United Kingdom
facility: University College London Hospital
city: Manchester
country: United Kingdom
facility: The Christie, Manchester
city: Milton Keynes
country: United Kingdom
facility: Milton Keynes General Hospital
city: Newcastle
country: United Kingdom
facility: Freeman Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospital
city: Oxford
country: United Kingdom
facility: Churchill Hospital
city: Poole
country: United Kingdom
facility: Poole Hospital
city: Sheffield
country: United Kingdom
facility: Weston Park
city: Southampton
country: United Kingdom
facility: University of Southampton Hospital
city: Swansea
country: United Kingdom
facility: Singleton Hospital
Study officials:
affiliation: NHS Greater Glasgow and Clyde
name: Janet Graham
role: PRINCIPAL_INVESTIGATOR
References: