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The Theranostic Value of STARD3 in Colorectal Cancer: The STAR Study

Recruiting
Conditions
Colorectal Cancer
Registration Number
NCT06136949
Lead Sponsor
Centro di Riferimento Oncologico - Aviano
Brief Summary

This study aims at verifying the overexpression of STARD3 in both early and advanced CRC patients derived tissues, to identify the pathways underpinning tumorigenesis and cancer progression in which STARD3 is involved. Moreover its role as a dynamic biomarker of treatment response and its part in treatment sensitivity will be explored.

Detailed Description

Colorectal cancer (CRC) is one of the most prevalent and deadly tumours in both men and women worldwide. An RNAi screening on 214 potential oncogenes described by the TCGA was performed and STARD3 was identified as potential theranostic target in mCRC. Considering the effects on cell viability and the druggability, STARD3 represents a strong candidate as a valid diagnostic and therapeutic target for mCRC patients.

In recent years, organoids have become a research hotspot, showing a significant potential in the biological analysis of tumours. Patient derived organoids could be a viable platform to test clinically available drugs and/or promising new molecules to explore tumour sensitivity in an ex-vivo model.

This is a longitudinal observational study on CRC patients derived tissues to verify the overexpression of STARD3 in both early and advanced CRC patients, to identify the pathways underpinning tumorigenesis and cancer progression in which STARD3 is involved through the development of cancer derived organoids, to explore its role as a dynamic biomarker of treatment response and to demonstrate its part in treatment sensitivity measured in tumour derived organoids compared to drug sensitivity observed in real-world patients.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
150
Inclusion Criteria
  • Histologically confirmed diagnosis of colorectal cancer, independently from diagnosis stage.
  • Age ≥18 years.
  • Signed informed consent form.
  • Availability of tissue and blood samples stored at the Institutional Biobank for research purposes.
Exclusion Criteria
  • Patients for which the tumour biobanking process could compromise the diagnostic assessments.
  • Pregnancy or breast-feeding.
  • History of concomitant or previous malignancy in the previous 5 years, except for adequately treated cutaneous squamous cell carcinoma or surgically removed in situ cervical carcinoma.

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Frequency of overexpression of STARD3 in both early and advanced CRC patientsat enrolment

Frequency of STARD3 overexpression in both early and advanced CRC patients

Secondary Outcome Measures
NameTimeMethod
Relation between presence of STARD3 overexpression and Overall survival (OSfrom enrolment to at least 5 years

relation between presence of STARD3 overexpression (dichotomic variable) and Overall survival (OS) defined as time between enrollment and death, using Kaplan Meyer method

Difference in the mean variation of STARD3 level in patients receiving oncologic treatment, evaluated from start of treatment to the first revaluation and to disease progressionfrom enrolment to at least 5 years

Difference in the mean variation of STARD3 level in patients receiving oncologic treatment, evaluated from start of treatment to the first revaluation and to disease progression

Presence of STARD3 overexpression as a prognostic factorfrom enrolment to at least 5 years

relation between presence of STARD3 overexpression (dichotomic variable) and disease-free survival (DFS) defined as time between enrollment and objective tumor progression using Kaplan Meyer method

Relation between presence of STARD3 overexpression and progression-free survival (PFS)from enrolment to at least 5 years

relation between presence of STARD3 overexpression (dichotomic variable) and progression-free survival (PFS) defined as time between enrollment and objective tumor progression or death whichever comes first, using Kaplan Meyer method

Concordance between the presence of selected molecular alterations on primary tumour tissues and organoidsup to 5 years

Concordance between the presence of selected molecular alterations on primary tumour tissues and organoids, frequencies will be reported and Cohen's Kappa will be calculated.

relation between variation of STARD3 overexpression and progression-free survival (PFS)from enrolment to at least 5 years

relation between variation of STARD3 overexpression (dichotomic variable) and progression-free survival (PFS) defined as time between enrollment and objective tumor progression or death whichever comes first, using Kaplan Meyer method

Demonstrate treatment sensitivity measured in tumour derived organoidsup to 5 years

Description of IC50 value (inhibitory concentration 50) for each drug tested on tumour-derived organoids

Relation between treatment sensitivity measured in tumour derived organoids and treatment sensitivity in patientsup to 5 years

Relation between IC50 (inhibitory concentration 50) calculated for each drug tested on patients' tumour-derived organoids and PFS of patients defined as time between enrollment and objective tumor progression or death whichever comes first. Relation will be measured with Hazard Ratio (HR)

Frequencies of overexpression or downregulation of selected genes alteration related to STARD3 overexpressionup to 5 years

Frequencies of overexpression or downregulation of selected genes alteration related to STARD3 overexpression. This analysis will be carried out in organoids cancer model

Variation of STARD3 as a prognostic factorfrom enrolment to at least 5 years

STARD3 expression could change over the time and affect disease-free survival (DFS). Relation between variation of STARD3 overexpression (dichotomic variable) and DFS (defined as time between enrollment and objective tumor progression) will be accessed with Kaplan Meyer method.

Relation between variation of STARD3 overexpression and Overall survival (OS)from enrolment to at least 5 years

Relation between variation of STARD3 overexpression (dichotomic variable) and Overall survival (OS) defined as time between enrollment and death, using Kaplan Meyer method

Trial Locations

Locations (1)

Centro di Riferimento Oncologico (CRO) di Aviano - IRCCS

🇮🇹

Aviano, Pordenone, Italy

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