Clinical trial · Observational
Prospective Validation of a DNA Damage Repair-Hippo Pathway Signature in Patients With Advanced Gastric Cancer
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
We envisioned a scenario where the interaction between the ATM-Chk2/ATR-Chk1 pathways and Hippo enables GC cells to overcome chemotherapy-induced death stimuli. First, ATM-Chk2 and ATR-Chk1 were found to be activated across all the GC molecular subtypes. Moreover, a number of genes associated with their basal activation are recurrently mutated or amplified. Thus, we retrospectively characterized a cohort of GC patients treated with first-line therapy for DDR- and Hippo-related markers, identifying a signature predicting inferior PFS and OS. This exploratory analysis provided the necessary information (frequency of candidate biomarkers and effect difference between groups) for a prospective study with validation purposes, which is the main goal of this trial.
Conditions
Conditions (2)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| DNA Damage | — | UNRESOLVED | — |
| Gastric Cancer | Malignant Gastric Neoplasm | CURATED_BROADER | 0.80 |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| investigated biomarkers regarding the efficacy of first-line chemotherapy | Diagnostic Test | — | UNRESOLVED |
Design
Arms and outcomes
Arms (1)
- label
- Popolation
- interventionNames
- Diagnostic Test: investigated biomarkers regarding the efficacy of first-line chemotherapy
Primary outcomes (3)
- measure
- Identify new biomarkers that predict the activity of first-line chemotherapy, in order to achieve better patient selection.
- timeFrame
- Three years
- description
- Computational enrichment analysis will be carried out to test whether tumors of patients with shorter PFS contain a higher-than-randomly-expected representation of a specific pathway/function. Special emphasis will be placed on, but not limited to, the DDR-Hippo-Wnt pathways. For multiple hypothesis testing a Benjamini-Hochberg False Discovery Rate correction will be applied (\<5%). For clinical data analysis, the Pearson's Chi-squared test of independence (2-tailed) and the Pearson's correlation coefficient will be used to assess the relationships between categorical and continuous variables, respectively.
- measure
- Identify additional genetic events molecularly linked to the DDR-Hippo signature and potentially improve its predictive ability.
- timeFrame
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria: * Age \>18 years; * Histologic diagnosis of locally advanced or metastatic gastric carcinoma (GC) or gastroesophageal junction carcinoma (EJC); * Biological material adequate for molecular analysis to be performed, taken (at surgery or by biopsy) prior to the administration of any anti-tumor treatment (chemotherapy and/or radiotherapy); * ECOG PS 0-2; * Adequate hematologic, hepatic, and renal function; * Measurable disease according to RECIST criteria; * Written informed consent. Exclusion Criteria: * Previous chemotherapy for metastatic disease; * Comorbidities not controlled with appropriate medical therapy; * Brain metastasis; * Patient unable to give adequate consent for the study
References
Publications (0)
Data not yet available