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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
150
Chemotherapy
Chemotherapy
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Northwell Health
New Hyde Park, New York, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
BC Cancer Agency Vancouver
Vancouver, British Columbia, Canada
Princess Margaret Cancer Centre
Toronto, Ontario, Canada
Progression free survival(PFS) in mFFX and GA arms pancreatic ductal adenocarcinoma (PDAC) in a randomized phase II trial.
Time from the date of randomization to progression based on the radiology assessment of response using RECIST v1.1, or death, whichever is earlier
Time frame: 2-4 years
ORR by RECIST 1.1 and duration of response in patients receiving mFFX or GA
percentage of patient's measurable disease who have achieved either complete response (CR) or partial response (PR)
Time frame: 2-4 years
Overall survival (OS) associated with mFFX or GA profiles, signatures and pharmacotyping
Time frame: 2-4 years
GATA6 as a biomarker of response to mFFX or GA
Time frame: 2-4 years
• Concordance between organoid transcriptomic profiles (RNAseq) and patient transcriptomic profiles (descriptive statistics)
Time frame: 2-4 years
• Concordance between chemotherapy sensitivity signature predictions and response to first line treatment (descriptive statistics).
Time frame: 2-4 years
• Correlation of individual tumour cytokeratins (eg. CK5 and CK17 expression) with chemotherapy response and resistance
Time frame: 2-4 years
Cell free circulating tumor (ct) DNA analysis (including KRAS mutational status)
Time frame: 2-4 years
Cluster Tendency analysis using artificial neural networks and radiomic methods combined
Time frame: 2-4 years
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