Title: PRIMUS-004: Second line chemotherapy for metastatic pancreatic cancer
Funder: Cancer Research UK

Abstract: Background Pancreatic cancer (PC) is the third most common cause of cancer related death in the western societies, and soon to become the second within a decade. While there are increasing number of first line therapeutic regimen options through various clinical trials, the therapeutic options for patients with PC going onto 2nd line treatment remains to be limited. Aims The aim of proposed PRIMUS-004 umbrella is to offer a range of second-line studies with extensive molecular profiling and evaluation of candidate selection biomarkers. Methods PRIMUS-004 will form part of the Precision-Panc PRIMUS clinical trial portfolio. Eligible patients for second line treatment will be screened, biopsied, and molecularly profiled on the Master Protocol, and allocated on one of the suitable second-line studies in the umbrella. The overall generic design for PRIMUS-004 is an umbrella of single arm phase II studies for experimental agents/combinations each using predictive probability design with 3 interim analyses allowing for early stopping for futility/efficacy. This approach has good power (87%) to detect response rates of 25%, but allows early stopping if response rate are low (10%). Initially each phase II looks at all putative biomarker subgroups overall, but subsequently allows recruitment to be focussed on or stopped in particular subgroups depending on the observed results. The aim of the design is provide flexibility to identify responsive biomarker subgroups within a structured statistical design. The phase II element of each may be preceded by a phase I safety run-in. Primary Endpoint • Overall response rate (ORR) Secondary Endpoints • Efficacy in terms of progression free survival (PFS) and overall survival (OS) • Safety profile. How the results of this research will be used Promising results from PRIMUS004 will lead to the design of later phase confirmatory trials which may be randomised. These later randomised studies may include further examination of the predictive value of the putative biomarkers, but the approach will be tailored based on the strength of the observed evidence from PRIMUS-004

Lay abstract: Background Pancreatic cancer (PC) is the third most common cause of cancer related death in the western societies, and soon to become the second within a decade. While there are increasing number of first line therapeutic regimen options through various clinical trials, the therapeutic options for patients with PC going onto 2nd line treatment remains to be limited. Aims The aim of proposed PRIMUS-004 umbrella is to offer a range of second-line studies with extensive molecular profiling and evaluation of candidate selection biomarkers. Methods PRIMUS-004 will form part of the Precision-Panc PRIMUS clinical trial portfolio. Eligible patients for second line treatment will be screened, biopsied, and molecularly profiled on the Master Protocol, and allocated on one of the suitable second-line studies in the umbrella. The overall generic design for PRIMUS-004 is an umbrella of single arm phase II studies for experimental agents/combinations each using predictive probability design with 3 interim analyses allowing for early stopping for futility/efficacy. This approach has good power (87%) to detect response rates of 25%, but allows early stopping if response rate are low (10%). Initially each phase II looks at all putative biomarker subgroups overall, but subsequently allows recruitment to be focussed on or stopped in particular subgroups depending on the observed results. The aim of the design is provide flexibility to identify responsive biomarker subgroups within a structured statistical design. The phase II element of each may be preceded by a phase I safety run-in. Primary Endpoint • Overall response rate (ORR) Secondary Endpoints • Efficacy in terms of progression free survival (PFS) and overall survival (OS) • Safety profile. How the results of this research will be used Promising results from PRIMUS004 will lead to the design of later phase confirmatory trials which may be randomised. These later randomised studies may include further examination of the predictive value of the putative biomarkers, but the approach will be tailored based on the strength of the observed evidence from PRIMUS-004

Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS