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 evaluatio
- Conditions
- Metastatic pancreatic cancerMedDRA version: 20.0 Level: LLT Classification code 10033605 Term: Pancreatic cancer metastatic System Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-004155-67-GB
- Lead Sponsor
- HS Greater Glasgow and Clyde
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 500
1Patient has been enrolled in the Precision Panc Master Protocol and their tissue has been deemed suitable for NGS analysis
2Patient has provided signed information consent for the PRIMUS 001 study
3Age = 16 years
4Histologically-confirmed metastatic pancreatic ductal adenocarcinoma and its varients, with measurable metastatic lesion(s) according to RECIST 1.1.
5Eastern Cooperative Oncology Group (ECOG) 0-1 with life expectation of no less than 12 weeks.
6Patients 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.
7Adequate liver/bone marrow function as defined by:
a.Neutrophils (ANC) = 1.5 x 109/l
b.Platelets = 100 x 109/l
c.Haemoglobin = 9.0 g/dL
d.WBC = 3 x 109/l
e.Total bilirubin = 1.5 x institutional ULN unless bilirubin rise is due to Gilbert’s syndrome
f.Aspartate transaminase (AST) and alanine aminotransferase (ALT) = 2.5 x ULN (and <5 ULN in the presence of liver metastases)
g.Estimated creatinine clearance = 60 mL/min (as calculated by Cockcroft and Gault or Wright formula or measured by EDTA clearance)
8Negative 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
9Woman 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.
10Compliant, 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)
11Patient must be biomarker positive as fed back after central Precision-PANC diagnostic testing
Are the trial subjects under 18? yes
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 170
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 330
1Prior treatment with nab-paclitaxel or oxaliplatin
2Prior chemotherapy for metastatic pancreatic cancer
3Known hypersensitivity for any component of any study drug
4Active infection including Herpes Zoster and chickenpox
5Current neuropathy = grade 2
6Uncontrolled brain metastatsis or mental illness
7Uncontrolled congestive heart failure (CHF), or history of myocardial ischemia (MI), unstable angina, stroke, or transient ischemia within previous 6 months.
8Uncontrolled serious contraindicated medical condition or illness
9Known or suspected dihydropyrimidine (DPD) deficiency
10Pregnant of breastfeeding
11History of physical or psychiatric disorder that would prevent informed consent and compliance with protocol
12Administration of any investigational drug within 28 days or 5 half-lives, whichever is longer, of receiving the first dose of trial treatment
13Any systemic anti-cancer therapy, or major surgery within 28 days of randomisation
14Any minor surgery or radiotherapy within 7 days of randomisation
15Any psychological, familial, sociological or geographical consideration potentially hampering compliance with the trial protocol and follow up schedule.
16Any patients receiving treatment with brivudin, sorivudin and analogues
17History of another malignancy in the last 5 years (other than treated squamous/basal cell skin cancer, treated early-stage cervical cancer or treated/bio
18chemically-stable, organ-confined prostate cancer).
19Any patient with severe diarrhoea (defined as =grade 3 diarrhoea despite maximum supportive measures and exclusion of underlying infection.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To provide a phase II assessment of efficacy of FOLFOX-A when compared to AG in both the biomarker-positive group and in all (unselected) patients, using progression free survival as the primary endpoint;Secondary Objective: To assess overall survival, safety, tolerability, quality of life and health economics between the two study groups;Primary end point(s): Progression free survival;Timepoint(s) of evaluation of this end point: CT scans will be performed every 8 weeks from randomisation until the patient progresses
- Secondary Outcome Measures
Name Time Method <br> Secondary end point(s): 1. Objective response rate (ORR) based on RECIST 1.1.<br> 2. Overall survival (OS)<br> 3. Safety and tolerability (toxicity NCI-CTCAE version 4.03)<br> 4. Quality of life (QoL) as assessed by EORTC QLQ-C30, QLQ-PAN26 and EQ-5D-5L.<br> 5. Peripheral neuropathy as assessed by the GOG-NTX4 questionnaire.<br> 6. Health economics (resource use) will be assessed during the course of the study<br> ;<br> Timepoint(s) of evaluation of this end point: 1 - CT scans will be performed every 8 weeks from randomisation until the patient progresses<br> 2, 4, 5 and 6 - will be assessed at every clinic visit during treatment and then at every follow up visit (3, 6, 9, 12, 18, 24, 36, 48 and 60 months post randomisation)<br> 3 - This will be assessed at every clinic visit and any adverse events will be followed up until resolution<br>