By obtaining clinical specimens from participants with triple negative breast cancer (TNBC), colorectal cancer (CRC), high grade serous ovarian cancer (HGSOC), and other select tumor types to establish and profile as freshly implanted tumors in mice, the aim of this study is to identify agents with predicted activity in the host patient while also potentially providing them with personalized cancer treatment options
Personalized patient-derived xenografts (pPDX) are increasingly used as tools for drug development in pre-clinical settings, and have been shown to recapitulate the histology and behavior of the cancers from which they are derived. Although, they have been commonly used productively as pre-clinical disease models to study disease biology and drug response, they have not been used prospectively to inform clinical management. pPDX have been employed to inform clinical decision-making in small studies, which have shown high concordance between individual pPDX and patient responses to therapy. While encouraging, the role of this approach in breast, colorectal, ovarian, and other cancer populations and in the context of genomic drug matching strategies remains undefined. This has created an opportunity to evaluate the utility of pPDX as clinical predictors to direct the use of chemo- and targeted therapies in combination with comprehensive genomic and epigenetic analysis for patients with TNBC, CRC, HGSOC and other selected tumor types.
Study Type
OBSERVATIONAL
Enrollment
120
Molecular profiling of host tumour sample and pPDX will be performed and analyzed by an expert panel. In vitro organoid culture generation may also be performed if sufficient fresh tissue is available. Matched treatment recommendation based on profiling and in vivo pPDX drug testing results will be made, if available. This recommendation will be communicated to the primary oncologist.
Princess Margaret Cancer Centre
Toronto, Ontario, Canada
RECRUITINGMeasure of drug sensitive pPDX to a panel of drugs as a predictor of clinical response in matched host
Sensitivity measured by tumor growth inhibition (\>80%) or objective tumor response (regression) as per Response Evaluation Criteria In Solid Tumors (RECIST) criteria.
Time frame: up to 5 years
Rate of results reporting
Time frame: up to 5 years
Rate of pPDX engraftment
Time frame: up to 2 years
Comparison of actionable alterations identified in clinical and pPDX samples
Genomic alterations identified using the Ion Proton System for Next-Generation Sequencing (NGS).
Time frame: up to 5 years
Number of patients with molecular abnormalities in pPDX as identified via NGS eliciting clinical responses while receiving matched treatments.
Overall accuracy of clinical responses as assessed by RECIST criteria in patient tumor.
Time frame: up to 5 years
Correlation between pPDX and organoid drug sensitivities
Time frame: up to 5 years
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.