Organoid-driven Chemotherapy Choice in Metastatic Pancreatic Cancer Patients.

Prof. Dr. med. Dres. h.c. Jan Schmidt, MME

Status and phase: Not yet enrolling; Phase 2

Conditions: Pancreatic Cancer Metastatic; Pancreatic Adenocarcinoma Metastatic; Pancreatic Neoplasms; Pancreas Neoplasms

Treatments: Drug: Organoid-guided treatment; Drug: Standard chemotherapy

Study type: Interventional

Funder types: Other

Identifiers

NCT06615830

HIPANC_002

Details and patient eligibility

About

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.

Enrollment: 185 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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)

Exclusion criteria

• 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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185 participants in 1 patient group

Organoid-driven second-line chemotherapy

Experimental group

Description:

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.

Treatment:

Drug: Standard chemotherapy

Drug: Organoid-guided treatment