Study protocol: multi-centre, randomised controlled clinical trial exploring stromal targeting in locally advanced pancreatic cancer; STARPAC2

• Published in: BMC cancer 2025-01, Vol.25 (1), p.106-8, Article 106
• Main Authors: Kocher, Hemant M, Sasieni, Peter, Corrie, Pippa, McNamara, Mairéad G, Sarker, Debashis, Froeling, Fieke E M, Christie, Alan, Gillmore, Roopinder, Khan, Khurum, Propper, David
• Format: Article
• Language: English
• Subjects: Adult; Aged; Albumins - administration & dosage; Albumins - therapeutic use; All-trans-retinoic acid (ATRA); Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Carcinoma, Pancreatic Ductal - drug therapy; Carcinoma, Pancreatic Ductal - mortality; Carcinoma, Pancreatic Ductal - pathology; Carcinoma, Pancreatic Ductal - surgery; Care and treatment; Chemotherapy; Chemotherapy, Combination; Clinical Trials, Phase II as Topic; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; Deoxycytidine - therapeutic use; Development and progression; Diagnosis; Female; Gemcitabine; Gemcitabine and nab-paclitaxel (GEM-NABP); Humans; Locally advanced pancreatic ductal adenocarcinoma (laPDAC); Male; Metastasis; Middle Aged; Multicenter Studies as Topic; Paclitaxel - administration & dosage; Paclitaxel - therapeutic use; Palliative treatment; Pancreatic cancer; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - mortality; Pancreatic Neoplasms - pathology; Pancreatic Neoplasms - surgery; Patient outcomes; Progression; Progression-Free Survival; Randomized Controlled Trials as Topic; Stroma; Stromal Cells - pathology; Study Protocol; Tretinoin - administration & dosage; Tretinoin - therapeutic use
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-024-13333-z

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. 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. STARPAC2 aims to assess the role of stromal targeting in laPDAC. EudraCT: 2019-004231-23; NCT04241276; ISRCTN11503604.