Predictive Value of Transcriptome-based OncoTreat/Oncotarget and Organoid Testing in Metastatic Pancreatic Cancer.

NCT06615830 | Not Yet Recruiting DMC

• 1 other identifier: HIPANC_002
• Study Type: observational
• Target: 185
• Locations: 0 countries
• Sites: N/A

Brief Summary

Pancreatic cancer is burdened by a survival of barely 10% at 5 years. About 80% of new cases do not qualify for surgery due to either locally-advanced or metastatic disease. In patients with good performance status (PS), palliative first-line treatments mainly consist of combination regimens, such as FOLFIRINOX, modified FOLFIRINOX or Gemcitabine-Abraxane. For subjects with a poor PS, instead, guidelines recommend single-agent infusions (e.g. Gemcitabine, Capecitabine or 5-FU alone). Nevertheless, upon disease progression therapeutic options are still scarce and with limited sustained efficacy. Overall survival in metastatic pancreatic cancer ranges between 9.1 and 13.5 months, while progression-free survival under either FOLFIRINOX or Gemcitabine-Abraxane spans between 5.5 and 6.4 months. This timespan reduces even further when standard second-line regimens must be initiated upon disease progression. Nowadays, genomic and transcriptomic analysis are crucial tools in cancer research that enable the identification of genetic mutations and alterations that drive the development and progression of cancer. By studying the changes in the DNA and RNA sequences of cancer cells, researchers can gain insights into the underlying molecular mechanisms of cancer and identify potential therapeutic targets. Genomic analysis can identify specific mutations or alterations that are present in cancer cells, while transcriptomic analysis can reveal changes in gene expression that may be linked to disease progression or response to treatment. These analyses are an essential component for the development of precision medicine approaches, which aim to tailor cancer treatment to the individual genetic profile of each patient. PDOs can replicate in vitro the biological, genetic and molecular aspects of the primary tumour. Some of their advantages include their rapid growth compared to xenografts, the possibility to perform high-throughput drug screening, and their direct application to precision oncology by predicting best therapies. In this study they will be used as an in vitro comparator of the molecular tests to the clinical course of the patient. Overall, combining genomic and transcriptomic analysis with PDO technology in cancer research might lead to exponential capacity to provide oncologic patients with extremely tailored and effective cancer treatments in the future. For HIPANC-002 these tests are being evaluated as non-interventional investigational IVD's. Test results are not to be used for protocol mandated therapy decisions.

Conditions

Pancreas Neoplasms; Pancreatic Neoplasms; Pancreatic Cancer Metastatic; Pancreatic Adenocarcinoma Metastatic

Keywords

Pancreatic cancer; Pancreatic adenocarcinoma; Metastatic pancreatic adenocarcinoma; Organoid; Organoid-driven chemotherapy; Darwin Oncotreat; Darwin Oncotarget; Personalized chemotherapy

Outcome Measures

Primary Outcomes (1)

• Is there a significant correlation between Oncotarget/Oncotreat based predicted drug sensitivity and the patient's progression-free survival (PFS) in metastatic pancreatic adenocarcinoma after administered standard therapy ?

  To demonstrate a significant correlation between the degree of sensitivity predicted by Oncotreat/Oncotarget 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.

  From enrollment to disease progression according to the RECIST v1.1 criteria, assessed up to 100 months

Secondary Outcomes (1)

• 1) Correlation between Darwin-test predicted drug sensitivity and patient-derived PDO sensitivity to clinically used drug regimens. 2) Correlation between the measured PDO sensitivity to the administered standard therapies 3) Biobanking

  Observation until progression under given standard treatment using RECIST and TU markers. Follow up until progression and/or death at least 60 months.

Study Arms (1)

Predictive value of Oncotreat/Oncotarget testing in palliative chemotherapy in pancreatic cancer

The study 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 Oncotreat and Oncotarget tests as well as for patient-derived organoids on which potentially predicted drugs will be benchmarked. Each patient will receive the standard first-line and second-line chemotherapy (chosen among Gemcitabine-Abraxane, or Abraxane-Gemcitabine-FOLFOX or FOLFIRINOX, based on the clinical judgement of the treating oncologist). When progression occurs predictive value of the test with regard to Progression-free Survival (PFS) will be analyzed.

Interventions

Standard chemotherapy

Organoid-guided treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

All patients with the diagnosis of metastatic adenocarcinoma of the pancreas can be enrolled provided the above mentioned criteria apply. The patients can either be therapy-naive or pretreated.

You may qualify if:

• 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)

You may not qualify if:

• Known allergies or intolerance to one or more compounds present in one of the first line or second line regimens
• 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

Sponsors & Collaborators

• Prof. Dr. med. Dres. h.c. Jan Schmidt, MME: lead
• Klinik Hirslanden, Zurich: collaborator
• Insel Gruppe AG, University Hospital Bern: collaborator
• Columbia Research Laboratories: collaborator

Related Publications (13)

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Biospecimen

Retention: SAMPLES WITH DNA

Pancreatic cancer tissue from metastasis

MeSH Terms

Conditions

Pancreatic Neoplasms

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Study Officials

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

  Swiss Surgery/Hirslanden Zurich

  STUDY DIRECTOR

Central Study Contacts

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

CONTACT

+ 41 442092505; jan.schmidt@hirslanden.ch

Alexander Siebenhüner, PD, MD

CONTACT

0041-44-387-3780; alexander.siebenhuener@hirslanden.ch

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. Dr. med. Dres. h.c. MME

Study Record Dates

• First Submitted: September 1, 2024
• First Posted: September 27, 2024
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): January 1, 2031
• Last Updated: February 11, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share