Organoid-driven Chemotherapy Choice in Metastatic Pancreatic Cancer Patients.
- Conditions
- Pancreas NeoplasmsPancreatic NeoplasmsPancreatic Cancer MetastaticPancreatic Adenocarcinoma Metastatic
- Interventions
- Drug: Standard chemotherapyDrug: Organoid-guided treatment
- Registration Number
- NCT06615830
- Lead Sponsor
- Prof. Dr. med. Dres. h.c. Jan Schmidt, MME
- Brief Summary
Pancreatic cancer is burdened by an extremely low survival rate. Survival chances reduce even further when the tumor spreads to other organs such as lymphnodes, liver or lungs. When the tumor cannot be surgically resected, the only valid curative option is represented by chemotherapy. However, therapies available to date have limited efficacy and they do not specifically target the biological characteristics of the tumor. The aim of the project is to validate a new technology called \"patient-derived organoids\" (PDOs) in predicting the best drugs for the treatment of pancreatic cancer based on the tumoral characteristics and behavior.
In order to generate PDOs a sample of tumoral tissue will be collected during a small surgical procedure, called laparoscopy. PDOs represent mini, three-dimensional copies of the original tumor, of which they maintain its behavior and aggressiveness. Through the DNA and RNA analysis of the tumor, the aim is to predict the best available drug by screening thousands of potentially effective compounds. Once identified, drugs will be tested in vitro on PDOs and the most efficient drug in controlling the tumor will be administered to the patient, once the present standard-of-care treatments fail.
Multiple benefits are expected from this trial. First of all, the most effective drug against their tumor based on an objective in vitro response will be provided. This might reflect in a better control of the disease and in a longer survival. Targeting the chemotherapy will also imply less side-effects due to unnecessary elevated chemotherapeutic dosages, which in turn will lead to a better compliance with the therapy. Eventually, all these aspects will reflect into a better quality of life.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 185
- Informed Consent as documented by signature
- Patients older than 18 years
- Patients with metastatic pancreatic ductal adenocarcinoma
- At least one lesion amenable for surgical excisional biopsy
- ECOG Performance status 0-2
- Radiologically measurable disease
- Life expectancy > 3 months
- Absolute leucocyte count >1.5 G/l, platelets >100 G/l
- Serum creatinine <1.5 times of the upper limit of normal or Clearance >50ml/min (according to the CKD-EPI formula)
- Known allergies or intolerance to one or more compounds present in one of the 3 first line regimens approved for the trial
- 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
- Active viral infection from HIV, HBV or HCV, even if under antiretroviral treatment
- Myocardial infarction within the previous 6 months
- Patients who are pregnant or breastfeeding
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Organoid-driven second-line chemotherapy Standard chemotherapy The arm will include patients with diagnosis of metastatic pancreatic adenocarcinoma. After complete disease staging, patients will undergo laparoscopic surgical biopsy of metastatic tumoral tissue. The tissue will serve for the generation of patient-derived organoids on which potentially effective drugs will be benchmarked. Each patient will receive the standard first-line chemotherapy (chosen among Gemcitabine-Abraxane, or Abraxane-Gemcitabine-FOLFOX or FOLFIRINOX, based on the clinical judgement of the treating oncologist). Upon disease progression, the drug predicted to be the most effective agent will be implemented as second-line therapy. Organoid-driven second-line chemotherapy Organoid-guided treatment The arm will include patients with diagnosis of metastatic pancreatic adenocarcinoma. After complete disease staging, patients will undergo laparoscopic surgical biopsy of metastatic tumoral tissue. The tissue will serve for the generation of patient-derived organoids on which potentially effective drugs will be benchmarked. Each patient will receive the standard first-line chemotherapy (chosen among Gemcitabine-Abraxane, or Abraxane-Gemcitabine-FOLFOX or FOLFIRINOX, based on the clinical judgement of the treating oncologist). Upon disease progression, the drug predicted to be the most effective agent will be implemented as second-line therapy.
- Primary Outcome Measures
Name Time Method Organoid sensitivity to first-line regimens ad progression-free survival From enrollment to disease progression according to the RECIST v1.1 criteria, assessed up to 100 months To demonstrate a significant correlation between the degree of sensitivity predicted by PDOs to Gemcitabine-Abraxane, or Abraxane-Gemcitabine-FOLFOX (according to the SEQUENCE trial) or FOLFIRINOX (according to the NAPOLI-3 trial), and clinical progression free survival (PFS) in metastatic pancreatic adenocarcinoma.
- Secondary Outcome Measures
Name Time Method Linear versus non-linear relationship between organoid sensitivity and progression-free survival From patient-derived organoid generation to completion of drug benchmarking assessed up to 100 months Explore graphically and statistically whether the relationship between PDOs sensitivity to second-line, targeted regimens and PFS has a linear or non-linear shape.
Within-subjects progression-free survival comparison From patient enrollment until second disease progression according to the RECIST v1.1 criteria, assessed up to 100 months Compare progression-free survival in months between second-line, targeted regimens with first-line, standard therapy.
Quality of life From enrollment to the second disease progression according to the RECIST v1.1 criteria, assessed up to 100 months Assess quality of life under standard and targeted chemotherapy.
Biobanking Biological samples will be biobanked up to 5 years Collect samples for biobanking and further identification of potential markers associated with tumor response (e.g. circulating tumoral DNA).
Rate of newly-identified compound From patient-derived organoid generation to completion of drug benchmarking, through study completion, an average of 1 year Assess the rate of compounds identified by patient-derived organoids, which are not routinely used by treating oncologists or accepted by insurances for reimbursement.
Second-line, most effective regimen in vitro prediction From patient-derived organoid generation to completion of drug benchmarking, through study completion, assessed up to 100 months Assess, through patient-derived organoids benchmarking, the most effective second-line chemotherapeutic regimen according to the presence of genetic signatures (at DNA and RNA level) associated with treatment response.