1. Feasibility of the process (Time Frame - 30 days after the last patient enrollment.): To determine the proportion of patients (specifically, the percentage with respect to the total sample enrolled in the study) for which organoids can be successfully generated and in which an effective treatment can be identified by drug screens in these patient-derived organoids. Successful generation of organoids will be defined as the presence of individual three-dimensional structures within 10 days from the begin of generation process. Effective treatment is considered a treatment decreasing of 50% (or more) the viability of patient-derived organoids.
Secondary outcome:
1. Safety of surgical biopsy and post-operative surgical complications. (Time Frame - 30 days post-operatively): To evaluate safety of surgical biopsy for patient-derived organoids generation in patients with pancreatic cancer. Safety will be evaluated in terms of absolute and relative (%) number of postoperative complications. Severity will be graded according the Clavien-Dindo classification for surgical complications: complications equal to or greater than grade 3B will be considered as "severe". Management of each complication will be recorded for descriptive purposes.
2. Contamination rates (Time Frame - 30 days after the last patient enrollment.): To assess the rate of contaminated samples by endogenous bacterial and fungal flora and to highlight possible implications in patient-derived organoid testing response.
3. Chemosensitivity testing (Time Frame - 6 days after the last organoid generation): To assess in vitro efficacy of different chemotherapeutic regimens (and their combinations). In vitro efficacy will be evaluated based on the drug's (or drug combination's) capacity to decrease organoid viability of more than 50% after 6 days from their administration. Drugs (or their combination) tested in vitro will include Oxaliplatin, Carboplatin, Cisplatin, SN-38 (Irinotecan), Leucovorin, 5-FU, Gemcitabine, Olaparib, Nab-Paclitaxel, Nanoliposomal irinotecan (Nal-IRI), Niraparib.
Surgical biopsy of tumoral tissue for organoid generation: In surgically-resectable lesions, tumoral samples will be collected from the main surgical specimens, before sending it for final pathological examination. Patients with metastatic disease, will be offered to undergo port-a-cath implantation for chemotherapy delivery and concomitant laparoscopic surgical excisional biopsy of suspicious metastatic lesions. Intraoperative frozen section will confirm the presence of malignant cells in the sample. Part of the specimen will be sent for assessment of contamination by bacterial and/or fungal flora by the Microbiology Laboratory. The remaining tumour sample will be sent for patient-derived organoid (PDO) formation. Two patients' blood samples will be retrieved in ethylenediaminetetraacetic acid (EDTA) tubes and will be sent with the surgical specimen. All patients will then receive the standard of care (SOC) treatment according to the clinical judgement of the oncologist in charge, always within the framework of the international guidelines.
Quelle: ClinicalTrials.gov
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"Patient-derived Organoids Drug Screen in Pancreatic Cancer"
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