Pancreatic Adenocarcinoma Signature Stratification for Treatment

Titre officiel

Pancreatic Adenocarcinoma Signature Stratification for Treatment

Sommaire:

Il s’agit d’un essai de phase II multicentrique et à répartition aléatoire comprenant un élément de transfert de grande taille. L’essai évaluera les deux schémas chimiothérapeutiques : folfirinox modifié (FFXm) et gemcitabine plus du nab‑paclitaxel (G/NP) chez les patients atteints d’un adénocarcinome canalaire pancréatique métastatique. Un certain nombre de composantes de laboratoire, y compris le profilage moléculaire, l’établissement organoïde dérivé du patient, la sensibilité aux essais de médicaments et d’autres biomarqueurs, sont intégrées à cet essai de phase II.

Description de l'essai

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.

Voir cet essai sur ClinicalTrials.gov