Pathogenic Variants in Homologous Recombination Repair Genes in Patients With Epithelial Ovarian Cancer

NCT04716374 | Completed

• 1 other identifier: Ovarian_ΗΕ4G/20
• Study Type: observational
• Target: 550
• Locations: 0 countries
• Sites: N/A

Brief Summary

Molecular alterations in Homologous Recombination Repair (HRR) genes have been associated with clinical benefit from chemotherapy and/or Poly (ADP-ribose) polymerase (PARP) inhibitors in patients with epithelial ovarian cancer. Therefore, the performance of tumor molecular profiling is currently recommended by international guidelines at initial diagnosis, among other reasons, for the modification of the treatment plan. The investigators' hypothesis was that tumor molecular profiling reveals additional parameters that can improve the predictive and prognostic role of the mere presence of HRR gene mutations. The study aimed to investigate the prognostic and predictive role of clonality of pathogenic variants in HRR genes and/or concurrent pathogenic variants in other clinically relevant genes.

Conditions

Epithelial Ovarian Cancer

Keywords

Epithelial ovarian cancer; Next Generation Sequencing (NGS); Pathogenic variants; Tumor molecular profiling; Clonality; Homologous recombination repair

Outcome Measures

Primary Outcomes (1)

• Overall survival

  The time from ovarian cancer diagnosis to the date of death from any cause

  Through study completion, an average of 3 years

Secondary Outcomes (1)

• Progression-free survival

  From date of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 96 months

Study Arms (1)

Patients with epithelial ovarian cancer

Patients with epithelial ovarian adenocarcinoma with archival tumor tissue available for analysis were identified through the Hellenic Cooperative Oncology Group (HeCOG)'s tumor repository. Patients had received treatment at HeCOG-affiliated institutions following standard international guidelines.

Other: Tumor molecular profiling

Interventions

Tumor molecular profiling OTHER

Tumor tissue processing and all NGS genotyping were performed at the Laboratory of Molecular Oncology (Hellenic Foundation for Cancer Research / AUTH). Paraffin H\&E sections from the retrieved tissue blocks were centrally reviewed for tumor histology and tissue adequacy for DNA extraction and were marked for macrodissection along with tumor DNA content \[(former tumor cell content (TCC%)\] assessment. DNA was extracted from macrodissected tissue fragments with the QIAamp® DNA mini kit (Qiagen, Hilden, Germany), measured in a Qubit fluorometer (Thermo Fisher Scientific, Paisley, UK), and genotyped with NGS in an Ion Torrent Proton sequencer (Thermo Fisher Scientific) by using a previously published custom panel (Kotoula, Lakis et al. 2019). Following stringent variant quality filtering (Kotoula, Chatzopoulos et al. 2021), 500 tumors

Also known as: NGS

Patients with epithelial ovarian cancer

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with epithelial ovarian adenocarcinoma with archival tumor tissue available for analysis were identified through the Hellenic Cooperative Oncology Group (HeCOG)'s tumor repository. Patients had received treatment at HeCOG-affiliated institutions from following standard international guidelines. In total, 501 patients with ovarian adenocarcinoma were included in the study (median age at ovarian cancer diagnosis was 58 years). Tumor histological types included predominantly high-grade serous, followed by endometrioid and clear cell carcinomas. All except 3 patients underwent surgery at initial diagnosis, most commonly total abdominal hysterectomy with bilateral salpingo-oophorectomy.

You may qualify if:

• Diagnosed with epithelial ovarian cancer
• Received treatment at HeCOG-affiliated institutions
• Have signed informed consent
• With adequate tumor tissue for analysis

Sponsors & Collaborators

• Hellenic Cooperative Oncology Group: lead

Related Publications (1)

• Fountzilas E, Kotoula V, Koliou GA, Liontos M, Papadopoulou K, Giannoulatou E, Papanikolaou A, Tikas I, Chrisafi S, Mauri D, Chatzopoulos K, Fostira F, Pectasides D, Oikonomopoulos G, Aivazi D, Andrikopoulou A, Visvikis A, Aravantinos G, Zagouri F, Fountzilas G. Tumor Genotyping and Homologous Recombination Repair Gene Variants in Patients With Epithelial Ovarian Cancer: Is Pathogenic Enough? Front Oncol. 2021 Jun 1;11:683057. doi: 10.3389/fonc.2021.683057. eCollection 2021.

  PMID: 34141624 DERIVED

MeSH Terms

Conditions

Carcinoma, Ovarian Epithelial

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Ovarian Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Study Officials

• ELENA FOUNTZILAS, MD

  HeCOG

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2020
• First Posted: January 20, 2021
• Study Start: January 1, 2004
• Primary Completion: January 1, 2013
• Study Completion: December 1, 2019
• Last Updated: January 20, 2021

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share