Impact of Different BRCA1/2 Gene Variants on Response to Therapy and Prognosis of Ovarian Cancer

NCT ID: NCT06775470

Last Updated: 2025-01-15

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 300 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-07-01
• Study Completion Date: 2025-12-31

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.

Conditions

Ovarian Cancer

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Interventions

Patients must have been diagnosed with ovarian cancer and be BRCA positive

Patients must have been diagnosed with ovarian carcinoma by 31/12/2021, have undergone BRCA testing at the UOC of Medical Genetics of the IRCCS AOU of Bologna Policlinico S. Orsola by 31/12/2021 and have been taken on for follow-up and/or treatment at the Medical Oncology - Zamagni and/or Gynaecological Oncology - De Iaco 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.

Intervention Type: DIAGNOSTIC_TEST

BRCA1 and BRCA2 positive, and be affected by Ovarian Cancer

Patients must have been diagnosed with ovarian carcinoma by 31/12/2021, have undergone BRCA testing at the UOC of Medical Genetics of the IRCCS AOU of Bologna Policlinico S. Orsola by 31/12/2021 and have been taken on for follow-up and/or treatment at the Medical Oncology - Zamagni and/or Gynaecological Oncology - De Iaco 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.

Intervention Type: DIAGNOSTIC_TEST

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.

• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

IRCCS Azienda Ospedaliero-Universitaria di Bologna

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Daniela Turchetti, MD

Role: PRINCIPAL_INVESTIGATOR

IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola

Locations

IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola

Bologna, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Daniela Turchetti, MD

Role: CONTACT

daniela.turchetti@unibo.it

+390512143694

Facility Contacts

Daniela Turchetti, MD

Role: primary

daniela.turchetti@unibo.it

+390512143694

Other Identifiers

IMBARCO

Identifier Type: -

Identifier Source: org_study_id