AIM – The aim of this study is to determine the effectiveness of a personalised treatment strategy, on the basis of a tumour molecular signature via genomic sequencing and protein expression, in patients with advanced recurrent or metastatic pancreatic adenocarcinoma as measured by progression free survival.

BACKGROUND – Median patient survival in metastatic pancreatic cancer is between three to four months and less than 5% of patients are alive at five years. There have been no major improvements in outcome over the last 20 years. Previous trials with targeted treatment in unselected patient populations demonstrated only modest improvements in survival over the current standard of care, gemcitabine. This may be due to lack of or inappropriate methods for patient selection. By selecting patients based on molecular phenotype and using treatments targeted at the associated aberrant signalling pathways the probability of response to targeted therapies is likely to be substantially higher.

Until recently there have been no biomarkers of potential clinical utility in pancreatic cancer, however several promising predictive and prognostic candidate biomarkers have emerged which satisfy requirements for progression to prospective testing. This study will work closely with the Australian Pancreatic Cancer Genome Initiative (APGI), which is contributing to the International Cancer Genome Consortium (ICGC; http://www.icgc.org/).

STUDY DESIGN – The IMPaCT trial is amultidisciplinary collaboration between the AGITG, NHMRC Clinical Trial Centre, Sydney Catalyst, and the Kinghorn Cancer Centre at the Garvan Institute of Medical Research, which houses the Australian Pancreatic Cancer Genome Initiative (APGI). 

Patients will be screened for actionable molecular phenotypes and randomized 1:1 to receive standard therapy (gemcitabine) or personalized treatment. Recruitment to the IMPACT trial is based on the following defined molecular phenotypes: 

- HER2/neu amplification: personalized treatment with gemcitabine + trastuzumab

- BRCA1, BRCA2, and PALB2 mutations: personalized treatment with 5-FU and mitomycin C

- KRAS wild type (incl codon 13 mutations): personalized treatment with gemcitabine + erlotinib

STUDY PROGRESS - The study will be conducted in two parts: an initial 20 patient pilot trial across 4 Australian sites assessing feasibility, followed by an additional 70 patients to assess progression (90 patients in total). The pilot study is now open and active. At the time of abstract submission, no patients were enrolled yet. A number of patients have been screened.

TRANSLATIONAL RESEARCH – Plasma and serum samples will be collected from patients at baseline and 4 weekly during treatment with a final sample at progression for future biomarker research. Blood for the circulating DNA sub-study is taken at baseline, weekly for the first cycle,  4 weekly during cycles 2 and 3, and then weekly until progression. The sub-study is using cutting edge techniques for the analysis of circulating tumour DNA in cancer patients