Patient-derived Organoids Drug Screen in Pancreatic Cancer

Study Overview
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Brief Summary
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Few chemotherapeutic options exist for pancreatic cancer. Moreover, objective criteria are lacking for deciding which regimen is more beneficial for patient presenting with metastases at diagnosis. This study investigates whether organoid generation from tumour samples of pancreatic cancer is a safe and feasible process for testing of multiple chemotherapy regimens in the laboratory. By participating to this study, patients will have a part of the tumour tissue retrieved and sent to the laboratory for organoid generation and drug testing. For surgically-resectable tumors, tumoral tissue samples will be collected from the main surgical specimens, before sending it for final pathological examination. In case of suspected metastatic lesion at diagnosis, curative surgery is not indicated. Therefore, we will offer patients to undergo port-a-cath implantation for chemotherapy delivery and concomitant laparoscopic surgical excisional biopsy of suspicious metastatic (either hepatic or peritoneal) lesions. At this stage of the study, the treatment that the patient will receive after surgery will not be affected by the results of the laboratory testing. In fact, all patients will receive the standard of care treatment based on the most recent oncologic guidelines and on the oncologist's clinical judgement. As part of the study, each patient will be followed for 30 days to assess possible surgical complications related to the surgical biopsy. This study will help to speed up the implementation of organoid generation in the clinical routine for the choice of the best treatment of patients affected by pancreatic cancer.

Official Title
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Patient-derived Organoid Generation in Pancreatic Cancer: a Single Centre, Open-label, Single Arm Feasibility Study

Conditions
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Pancreas Cancer, Pancreas Neoplasm, Pancreas Adenocarcinoma, Pancreatic Cancer, Pancreatic Neoplasms, Pancreatic Adenocarcinoma

Intervention / Treatment
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* Procedure: Surgical biopsy of tumoral tissue for organoid generation


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Written informed consent provided Patients older than 18 years Histologically- or cytologically-proven pancreatic ductal adenocarcinoma (PDAC) Tumour lesion amenable for laparoscopic, surgical biopsy Eastern Cooperative Oncology Group (ECOG) Performance status (PS) 0-2 Radiologically measurable disease Life expectancy > 3 months Absolute neutrophile count >1500/microL, platelets >100'000/microL Serum creatinine <1.5 times of the upper limit of normal or Clearance >50ml/min (according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula) Exclusion criteria: Concomitant need for full anticoagulation that cannot be interrupted or bridged prior to tissue biopsy ECOG PS >2 Heart failure (NYHA class III-IV) Severe or uncontrolled concurrent illness Myocardial infarction within the previous 6 months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Organoid generation<br>All patients will included in a single-arm. Participants will undergo biopsy of tumor tissue for subsequent organoid generation. | Procedure: Surgical biopsy of tumoral tissue for organoid generation<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of the process | 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. | 30 days after the last patient enrollment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of surgical biopsy and post-operative surgical complications. | 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. | 30 days post-operatively | 
| Contamination rates | To assess the rate of contaminated samples by endogenous bacterial and fungal flora and to highlight possible implications in patient-derived organoid testing response. | 30 days after the last patient enrollment. | 
| Chemosensitivity testing | 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. | 6 days after the last organoid generation |