- To study the success rate of organoid culture from lymph node, visceral and bone metastases in metastasized urogenital cancer and examine which parameters influence the success rate (culture media, biopsy site, cell counts). - To study the…
ID
Source
Brief title
Condition
- Renal and urinary tract neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Percentage of organoid cultures with >2 passages and percentage of
organoid-lines (>4 passages).
- Percentage of organoids in which the DNA profile shows strong concordance
with the DNA profile of biopsy tissue (>70% concordance regarding aberrations
of snvs/InDels/CNVs)
- Therapies for which a factor 3 difference in cell viability is found between
organoids with and organoids without aberrations in the targeted pathway.
Secondary outcome
Secundaire outcome measures:
- Percentage of organoid-lines per used culture medium
- Percentage of druggable aberrations in organoids
- Percentage of lymfocyte-organoid cocultures in which after 2 weeks an
increase in T cell activity is measured (INF-* ELISPOT)
Exploratory
- Concordance between organoids and biopsy tissue regarding immunological
landscape (variables: lymfocyte/tumor cell ratio, density T cell subsets,
expression of checkpoint molecules).
- Relation between immunological landscape and overall and progression-free
survival (Cox-proportional hazard analyse) (variables: lymfocyte/tumor cell
ratio, density T cell subsets, cytokine profile; expression of checkpoint
molecules)
- Impact of the above mentioned variables on response according to RECIST1.1
(CR/PR vs SD/PD) and drug-sensitivity analysis in organoids (>30% vs < 30%
decrease in cell viability) (T-test/Mann-Whitney U test + Bonferroni correction)
- Regression analysis to find predictors for response to immune checkpoint
inhibitors in organoids (lymfocyte/tumor cell ratio; density T cell subsets,
expression of checkpoint molecules; mutational/neoantigen load)
Background summary
Next-generation sequencing (NGS) led to important discoveries regarding the
moleculair landscape of patients with urogenital cancer and mechanisms of
resistance. However, implementation of biomarkers for urogenital cancer in
clinical practice has been limited so far. For prostate and bladder cancer,
several potential druggable aberrations are known. In the past years we gained
expercience in culturing three dimensional tumor models, called organoids.
Organoids can be used to test drugs ex-vivo and to determine the relevance of
specific mutations. Recently, the TULIP study indicated that the composition of
tumour-infiltrating lymphocytes in prostate cancer influences the response to
immunotherapy.
Study objective
- To study the success rate of organoid culture from lymph node, visceral and
bone metastases in metastasized urogenital cancer and examine which parameters
influence the success rate (culture media, biopsy site, cell counts).
- To study the concordance between the DNA profile of organoids and the DNA
profile in tumor biopsies of the same patient.
- To examine which molecular aberrations are druggable in organoids and how
frequently these aberrations are found
- To examine the feasibility of using lymfocyte-organoid cocultures for testing
immuuncheckpoint inhibitors.
- To correlate composition of tumour infiltrating immune cells and expression
of checkpoint molecules with response and survival data of patients with
metastasized urogenital cancer.
Study design
The PIONEER study is a prospective, translational research project in patients
with metastasized urogenital cancer. In patients who undergo a biopsy for
diagnostic or therapeutic purposes, one or two extra biopsies will be taken. We
will use this tissue for organoid culture and immunophenotyping. We will
selectively test drugs on organoids depending on the aberrations found during
NGS . We will use immunophenotyping to investigate whether composition of
tumour infiltrating immune cells and expression of checkpoint molecules
correlates with drug responses in urogenital cancer.
Study burden and risks
There is a small risk of complicaties due to the extra biopsies taken for this
study. The incidence of complications after biopsies is <5% and the incidence
of severe complications is < 1%. Possible complications include pain, bleeding
or infection. We do not expect the rate of complications to rise significantly
due to one or two extra biopsies.
There is a small chance that relevant, coincidental findings are discovered
during DNA sequencing, which could pose a psychological burden on patient
and/or relatives
Geert Grooteplein Zuid 8
Nijmegen 6500HB
NL
Geert Grooteplein Zuid 8
Nijmegen 6500HB
NL
Listed location countries
Age
Inclusion criteria
- Patients with metastasized bladder cancer or prostate cancer
Exclusion criteria
- Comorbidity that interferes with the safe removal of extra tissue.
- Objection against anonymized storage of tissue for an unlimited period of time.
- Objection against disclosure of relevant incidental findings (DNA sequencing).
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL67888.091.18 |