Clinical trial NCT06775470: Impact of Different BRCA1/2 Gene Variants on Response to Therapy and Prognosis of Ovarian Cancer
Official title: Impatto Delle Diverse Varianti Dei Geni BRCA1/2 su Risposta Alla Terapia e Prognosi Del Carcinoma Ovarico
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Ovarian Cancer
Keywords: BRCA1
BRCA2
PARP
Lead sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna
Sponsor class: OTHER
First posted: 2025-01-15
Enrollment: 300
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: From 2012 to the end of 2021, 869 patients underwent BRCA testing at the UOC of Medical Genetics of the IRCCS AOU of Bologna Policlinico S.Orsola 869 patients with CO, almost all of whom have given informed consent to the acquisition of clinical documentation relating to their case and to the use of their data for scientific purposes and about half of them were taken on for a period of at least 1 year at the Medical Oncology - Zamagni and/or the Gynaecological Oncology - De Iaco. The investigators estimated a sample of about 300 patients.

Brief summary: Identify any significant differences in terms of drug response and survival between the different possible alterations in the BRCA1/2 genes, in order to stratify ovarian cancer patients with a view to increasingly personalised and thus effective therapy.

Detailed description: Ovarian carcinoma (OC) is the leading cause of death among gynaecological neoplasms. It is, in fact, a neoplasm that is not very frequent but highly lethal: in Emilia-Romagna, the incidence is about 17 cases per 100,000 inhabitants and the mortality rate is around 15 cases per 100,000, with a very high mortality/incidence ratio (0.83). The high mortality rate is mainly due to the fact that, due to the non-specific and late symptoms, 75-80% of patients arrive at the diagnosis at an advanced stage of the disease (III-IV), characterised by a 5-year survival of less than 25%.

The primary therapeutic approach for this tumour is a combination of debulking surgery and platinum-based chemotherapy generally associated with taxanes, while as far as maintenance therapies are concerned, PARP inhibitors (PARPi), drugs capable of blocking a DNA repair mechanism alternative to that of homologous recombination, have been gaining in importance in recent years. They have proved particularly effective in tumours that present alterations in the BRCA1 and BRCA2 genes, which are key players in homologous recombination. For this reason, the detection of mutations in the BRCA1 and BRCA2 genes is predictive of the efficacy of PARPi maintenance therapy and, consequently, as of 2015, the BRCA test has been indicated in all women newly diagnosed with ovarian cancer (excluding borderline and mucinous forms), possibly from tumour tissue, given the evidence that in addition to constitutional (inherited) variants, somatic variants (acquired and tumour-confined), present in about 9%, are also associated with a PARPi benefit.

Recent data, however, have challenged the assumption that functionally significant variants for which a predisposing role has been demonstrated for hereditary breast and ovarian cancers are necessarily predictive of drug response. Furthermore, the fact that somatic mutations are present in only a limited fraction of the DNA copies analysed in a tumour suggests that there may be residual BRCA activity that compromises effective PARPi activity.

Eligibility criteria: Inclusion Criteria:

* ovarian cancer diagnosis by 31/12/2021;
* BRCA test at the UOC of Medical Genetics of the IRCCS AOU of Bologna Policlinico S.Orsola by 31/12/2021;
* follow-up and/or treatment at Medical Oncology and/or Gynaecological Oncology of the IRCCS Azienda Ospedaliero-Universitaria (AOU) of Bologna for a period of time of at least 1 year and by 31/12/2021 and for a minimum period of 6 months

Exclusion Criteria:

* ovarian carcinoma of 'mucinous' or 'borderline' histotype.

Primary outcomes:
measure: Differences in BRCA1/2 status for predictive response to chemotherapy
timeFrame: 12 months
Secondary outcomes:
measure: Differences in response to chemotherapy based on BRCA variant
timeFrame: 12 months
Other outcomes:
Locations:
city: Bologna
country: Italy
facility: IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola
Study officials:
affiliation: IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola
name: Daniela Turchetti, MD
role: PRINCIPAL_INVESTIGATOR
References: