Pancreatic Adenocarcinoma Signature Stratification for Treatment

Official Title

Pancreatic Adenocarcinoma Signature Stratification for Treatment

Summary:

This is a randomized multicentre phase II trial with a large translational component. The trial will evaluate the two standard chemotherapy regimens: modified folfirinox (mFFX) and gemcitabine/nab-paclitaxel (GA), in patients with untreated metastatic pancreatic ductal adenocarcinoma. Integrated into this phase II trial are a number of laboratory components including molecular profiling, patient derived organoid establishment, and drug testing sensitivity and other biomarkers.

Trial Description

Primary Outcome:

• Progression free survival(PFS) in mFFX and GA arms pancreatic ductal adenocarcinoma (PDAC) in a randomized phase II trial.

Secondary Outcome:

• ORR by RECIST 1.1 and duration of response in patients receiving mFFX or GA
• Overall survival (OS) associated with mFFX or GA profiles, signatures and pharmacotyping
• GATA6 as a biomarker of response to mFFX or GA
• • Concordance between organoid transcriptomic profiles (RNAseq) and patient transcriptomic profiles (descriptive statistics)
• • Concordance between chemotherapy sensitivity signature predictions and response to first line treatment (descriptive statistics).
• • Correlation of individual tumour cytokeratins (eg. CK5 and CK17 expression) with chemotherapy response and resistance
• Cell free circulating tumour (ct) DNA analysis (including KRAS mutational status)
• Cluster Tendency analysis using artificial neural networks and radiomic methods combined

The two chemotherapy regimens GA and mFFX remain standard treatment options without biomarkers to predict response. PASS-01 will for the first time explore progression free survival differences in the two standard backbone regimens used in the advanced setting. Biomarker driven strategies in pancreatic ductal adenocarcinoma (PDAC) are lacking, perhaps accounting for a large number of failed phase II studies. This study will evaluate two standard of care chemotherapy regimens, but will also explore high content molecular profiling, chemotherapy sensitivity signatures, GATA6 and other putative biomarkers as predictors of response to chemotherapy. In addition, the use of patient derived organoid models for personalized medicine in PDAC will continue to develop within this study. Approximately 150 patients diagnosed with untreated metastatic pancreatic cancer will be randomized to either arm.

View this trial on ClinicalTrials.gov