| Contributors: |
Barts Cancer Institute and Wolfson Institute of Public Health, Mary University of London, John Vane Science Centre, Charterhouse Square, London, Queen, EC1M 6BQ, UK. h.kocher@qmul.ac.uk. Barts Health NHS Trust, Whitechapel, London, E1 1BB, UK. h.kocher@qmul.ac.uk. Centre for Tumour Biology, Queen Mary University of LondonBarts Cancer Institute- aCRUK Centre of Excellence, Charterhouse Square, London, EC1M 6BQ, UK. h.kocher@qmul.ac.uk. Barts Cancer Institute and Wolfson Institute of Public Health, Mary University of London, John Vane Science Centre, Charterhouse Square, London, Queen, EC1M 6BQ, UK. Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK. Division of Cancer Sciences, Department of Medical Oncology, University of Manchester &, The Christie NHS Foundation Trust, Manchester, UK. Guy's and St Thomas' NHS Foundation Trust, London, UK. University of Glasgowand, NHS Greater Glasgow and Clyde , Glasgow, UK. Edinburgh Cancer Centre, NHS Lothian, Edinburgh, UK. Royal Free London NHS Foundation Trust, London, UK. University College London Hospitals NHS Foundation Trust, London, UK. Barts Health NHS Trust, Whitechapel, London, E1 1BB, UK. |
| Description: |
BACKGROUND: Pancreatic cancer (PDAC: pancreatic ductal adenocarcinoma, the commonest form), a lethal disease, is best treated with surgical excision but is feasible in less than a fifth of patients. Around a third of patients presentlocally advanced, inoperable, non-metastatic (laPDAC), whose stadrd of care is palliative chemotherapy; a small minority are down-sized sufficiently to enable surgical excision. We propose a phase II clinical trial to test whether a combination of standard chemotherapy (gemcitabine & nab-Paclitaxel: GEM-NABP) and repurposing All Trans Retinoic Acid (ATRA) to target the stroma may extend progression-free survival and enable successful surgical resection for patients with laPDAC, since data from phase IB clinical trial demonstrate safety of GEM-NABP-ATRA combination to patients with advanced PDAC with potential therapeutic benefit. METHODS: Patients with laPDAC will receive at least six cycles of GEM-NABP with 1:1 randomisation to receive this with or without ATRA to assess response, until progression or intolerance. Those with stable/responding disease may undergo surgical resection. Primary endpoint is progression free survival (PFS) defined as the time from the date of randomisation to the date of first documented tumour progression (response evaluation criteria in solid tumours [RECIST] v1.1) or death from any cause, whichever occurs first. Secondary endpoints include objective response rate (ORR), overall survival (OS), safety and tolerability, surgical resection rate, R0 surgical resection rate and patient reported outcome measures (PROMS) as measured by questionnaire EQ-5D-5L. Exploratory endpoints include a decrease or increase in CA19-9 and serum Vitamin A over time correlated with ORR, PFS, and OS. DISCUSSION: STARPAC2 aims to assess the role of stromal targeting in laPDAC. TRIAL REGISTRATION: EudraCT: 2019-004231-23; NCT04241276; ISRCTN11503604. |