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L1 chemotherapy regimen (FOLFIRINOX vs Gemcitabine plus nab-paclitaxel (GemnabP)) will be selected based on transcriptomic signatures applied to the pre-therapeutic biopsy of newly diagnosed PDAC patients.

Formalin-Fixed Paraffin-Embedded (FFPE) samples will be centralized in which nucleic acids extraction (DNA+RNA) and FFPE-compatible RNA-sequencing will be performed in real-time (≤28 days). RNAseq reads will be processed and all 5 transcriptomic signatures will be applied for prediction of response to 5FU, oxaliplatin, irinotecan, gemcitabine and taxane. In addition, biomarkers status will be obtained for all patients as part of good clinical practice.

Clinical value of 5 transcriptomic signatures to personalize the therapeutic decision for L1 in PDAC

Blood (serum and plasma) will be drawn at baseline, week 8, and tumor progression in order to look for surrogate biomarkers of tumor signatures in liquid biopsy

Biomarkers of tumor signatures (translational studies)

Cindy NEUZILLET, MD, PhD

Isabelle TURBIEZ

Louis DE MESTIER, MD

Charlotte FENIOUX, MD

Antony TURPIN, MD

Brice CHANEZ, MD

The aim of this study is to assess the clinical value of 5 transcriptomic signatures prognostic of chemotherapeutic sensitivity to improve the Objective Response Rate (ORR) of first-line (L1). Chemotherapy regimen (FOLFIRINOX vs Gem-nabP) will be selected based on transcriptomic signatures applied to the pre-therapeutic liver biopsy of newly diagnosed PDAC patients.

Step 1: patients will sign a 1st informed consent prospectively for the molecular screening (RNAseq profile). 5 transcriptomic signatures will be applied for prediction of response to 5 Fluoro-Uracil (5FU), oxaliplatin, irinotecan, gemcitabine and taxane. Biomarker status will be obtained for all patients as part of good clinical practice.

Patients will be eligible for prospective step 2 only if the transcriptomic analysis is informative and the treatment can be started within 28 days.

Step 2: study treatment strategy: based on the results of transcriptomic signatures, patients will receive either FOLFIRINOX or Gem-nabP according to the following algorithm (2nd informed consent):

* Predicted to be FOLFIRINOX sensitive (regardless of sensitivity to Gem-nabP) = FOLFIRINOX
* Predicted to be FOLFIRINOX and Gem-nabP resistant = FOLFIRINOX
* Presence of a germline breast cancer (BRCA) mutation (regardless of transcriptomic signature) = FOLFIRINOX (tumors sensitive to platinum).
* Predicted to be Gem-nabP sensitive and FOLFIRINOX resistant = Gem-nabP

Chemotherapy with FOLFIRINOX and Gemcitabine plus nab-paclitaxel will be administered as in routine practice, according to their approval. Dose adaptation will be allowed according to investigator's usual practice.

Personalized First-line Chemotherapy Choice in Advanced Pancreatic Adenocarcinoma Using Transcriptomic Signatures

Pilot Study of Personalized First-line Chemotherapy Choice for Patients With Advanced Pancreatic Adenocarcinoma Using Transcriptomic Signatures (PACsign)

Sponsor will share de-identified data sets. Documents generated under the project will be disseminated in accordance with Institut Curie policies.

ORR, defined as the percentage of patients whose disease decreased by at least 30% (partial response - PR) and/or disappeared (complete response - CR) under treatment among patients who start treatment.

PFS, defined as the time from the date of treatment initiation to the date of progression or death whatever the cause. Progression will be assessed by the investigator based on TAP-CT scan every 8 weeks according to RECIST v1.1.

OS, defined from the date of treatment initiation to the date of death whatever the cause.

DCR, defined as the percentage of patients who have achieved complete response, partial response or stable disease according to RECIST v1.1 among patients who start treatment.

Toxicities will be graded, according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0 (digestive, hematologic, neuropathy).

Spots Global Cancer Trial Database for clinical value of 5 transcriptomic signatures to personalize the therapeutic decision for l1 in pdac