PRIMUS 002 is looking at 2 different chemotherapy regimens in the neo-adjuvant setting for pancreatic cancer. Each treatment will be given for 3 months prior to surgery
This is an integrated, open label, non-randomised, phase II trial of 2 neo-adjuvant regimens (FOLFOX-A and AG) assessing efficacy and toxicity with integrated translational work. The study is powered on testing a proposed DNA damage response deficient biomarker for responsiveness in patients treated with FOLFOX-A; patients being treated with AG are recruited concurrently. The study has a prospective safety assessment of neo-adjuvant chemotherapy and neo-adjuvant chemotherapy followed by chemoradiotherapy consisting of conventional radiotherapy with concomitant capecitabine. This safety assessment will include all patients (FOLFOX-A and AG)
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
31
* nab-paclitaxel: 150mg/m2 IV over 30 minutes, day 1 (administered first). * Oxaliplatin: 85mg/m2, IV over 2 hours, day 1. * Folinic acid: 350mg flat dose, IV over 2 hours, day 1. * Fluorouracil 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 local practice.)
* nab-paclitaxel: 125mg/m2 IV over 30 minutes on days 1, 8 and 15 (administered first). * Gemcitabine 1000mg/m2 IV over 30 minutes on days 1, 8 and 15 (immediately following nab-paclitaxel).
Western General
Edinburgh, United Kingdom
Beatson West of Scotland Cancer Centre
Glasgow, United Kingdom
Royal Free Hospital
London, United Kingdom
Time to progression post FOLFOX-A induction treatment
date of progression after FOLFOX-A neo-adjuvant chemotherapy as assessed by RECIST 1.1
Time frame: CT scans will take place at baseline, pre chemoradiotherapy and pre surgery, over approximately 6 months
Proving liquid biopsies can be used to define patient subgroups
a liquid biopsy will be taken and analysed using circulating tumour DNA at different timepoints to see if these can be used to define patient subgroups
Time frame: From date of registration to date of surgery. On average 4 months after registration
Response post neo-adjuvant chemotherapy
CT scans will be reported to RECIST 1.1 and best response will be evaluated
Time frame: CT scan will be performed at baseline and then post neo-adjuvant chemotherapy (approximately 3 months later)
College of American Pathologists tumour regression grade
CAP tumour regression grade (grade 0-3 with 0 being no viable residual tumour and 3 being poor to no response) will be assessed post surgery
Time frame: Post surgery which will be approximately 4 months post registration
R0 rate post surgery
R0 rate will be assessed post surgery
Time frame: Post surgery which will be approximately 4 months post registration
Overall survival
Overall survival will be assessed in all patients
Time frame: From date of registration until date of death assessed for up to 5 years post registration
Disease free survival
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Disease free survival will be assessed at every follow up visit
Time frame: from date of registration until date of disease recurrence assessed for at least 24 months post registration
Safety and tolerability of study drugs: NCI CTCAE 4.03
Safety and tolerability will be assessed as per NCI CTCAE 4.03
Time frame: Assessed at every clinic visit during treatment, for approximately 3 months post registration
Safety and tolerability of chemoradiotherapy: NCI CTCAE 4.03
Safety and tolerability of chemoradiotherapy will be assessed as per NCI CTCAE 4.03
Time frame: Assessed at every chemoradiotherapy visit and pre-surgery (once Chemoradiotherapy added). Chemoradiotherapy will take place 5 days a week for three weeks
Surgical complication rate
Rate of surgical complication as assessed by NCI CTCAE 4.03
Time frame: Assessed post surgery, approximately 4 months post registration
Neurotoxicity
Assessed by GOG NTX4 (4 questions graded from 0 (not at all) to 4 (very much). quality of life will be assessed using the GOG NTX4 tool at the following timepoints: Baseline, month 1, month 2, month 3, pre chemoradiotherapy, between fraction 11 and 15 of chemoradiotherapy, pre surgery, at every follow-up visit (6, 9, 12 months post registration then every 6 months)
Time frame: Neurotoxicity will be assessed from registration until study is completed at various timepoints until patient death. Each patient will be followed up for at least 24 months post registration
Quality of life assessed by EORTC QLQ-C30
quality of life will be assessed using the EORTC QLQ C30 tool at the following timepoints: Baseline, month 1, month 2, month 3, pre chemoradiotherapy, between fraction 11 and 15 of chemoradiotherapy, pre surgery, at every follow-up visit (6, 9, 12 months post registration then every 6 months for a minimum of 24 months). The Quality of life tool is comprised of 28 questions that the patient answers either 1-4 (1 = not at all, 4 = Very much) and 2 questions that are on al scale of 1 - 7 where 1 = very poor and 7 = excellent
Time frame: Quality of life will be assessed from registration until study is completed at various timepoints until patient death. Each patient will be followed up for at least 24 months post registration
Quality of life assessed by EORTC QLQ-PAN26
quality of life will be assessed using the EORTC QLQ-PAN26 tool at the following timepoints: Baseline, month 1, month 2, month 3, pre chemoradiotherapy, between fraction 11 and 15 of chemoradiotherapy, pre surgery, at every follow-up visit (6, 9, 12 months post registration then every 6 months for a minimum of 24 months). The Quality of life tool is comprised of 26 questions that the patient answers either 1-4 (1 = not at all, 4 = Very much)
Time frame: Quality of life will be assessed from registration until study is completed at various timepoints until patient death. Each patient will be followed up for at least 24 months post registration
Health Economics
Health economics defined as number of visits to hospital per patient, both as an inpatient and as an outpatient will be assessed at the following timepoints: Baseline, month 1, month 2, month 3, pre chemoradiotherapy, between fraction 11 and 15 of chemoradiotherapy, pre surgery, at every follow-up visit (6, 9, 12 months post registration then every 6 months for a minimum of 24 months)
Time frame: Health economics will be assessed from registration until study is completed at various timepoints until patient death. Each patient will be followed up for at least 24 months post registration