Sub-type Specific Genomic Mutations in sBOTs

• ClinicalTrials.gov Identifier: NCT03883542
• Recruitment Status: Recruiting
• First Posted: March 21, 2019
• Last Update Posted: May 16, 2023
• Sponsor: Universitair Ziekenhuis Brussel
• Information provided by (Responsible Party): Stefan Cosyns, Universitair Ziekenhuis Brussel

Tracking Information

• First Submitted Date: February 26, 2019
• First Posted Date: March 21, 2019
• Last Update Posted Date: May 16, 2023
• Actual Study Start Date: January 2017
• Estimated Primary Completion Date: December 31, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 19, 2019)

genetic mutations [ Time Frame: 2020 ]

amount and type of genetic mutations in different subgroups will be analyzed and compared between the different subgroups. Are the mutations suggestive for a type I or type II pathway differentiation?

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Sub-type Specific Genomic Mutations in sBOTs
• Official Title: Sub-type Specific Genomic Mutations in Serous Borderline Ovarian Tumors

Brief Summary

The aim of this study is to identify different origin in carcinogenesis between serous borderline ovarian tumors presenting a. without implants, b. with non-invasive implants, c. with invasive implants and d. with micropapillary pattern.

The presence of specific mutations could suggest for a more aggressive primary treatment if a higher risk of recurrence can be expected.

Detailed Description

Introduction Borderline Ovarian Tumors (BOTs) behave indolently in the vast majority of cases and the prognosis is usually favorable. There is more evidence that two subtypes of BOTs represent a higher risk of recurrence or even progression to an invasive ovarian cancer. In case of a presentation with a micro-papillary grow pattern or when invasive implants are diagnosed the prognosis tend to be less favorable.

Genome sequencing in ovarian cancer helped to differentiate two different pathways in the carcinogenesis.

Low grade serous carcinomas evolving from adenofibromas or borderline tumors over non-invasive micropapillary serous borderline tumors to invasive micropapillary serous carcinoma, show frequent mutations in the Kirsten Rat Sarcoma gene (KRAS), B-Raf Kinase gene(BRAF), Erb-B2 Receptor Tyrosine Kinase 2 gene (ERBB2), Phosphatase and Tensin homolog gene (PTEN), Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha gene (PIK3CA) and Catenin Beta 1 gene (CTNNB1). This pathway is called Type I and is characterized by a slow step-wise process. These low-grade invasive tumors are indolent and are known with a better outcome than high-grade invasive tumors.

In contrast the Type II pathway development of invasive tumors is rapid and vast majority of tumors show a Tumor Protein p53 (TP53) mutation and loss of Breast Cancer type 1 susceptibility protein (BRCA1).

The aim of this study is to identify different origin in carcinogenesis between serous borderline ovarian tumors presenting a. without implants, b. with non-invasive implants, c. with invasive implants and d. with micropapillary pattern.

The presence of specific mutations could suggest for a more aggressive primary treatment if a higher risk of recurrence can be expected.

• Study Type: Observational
• Study Design: Observational Model: Case-Only; Time Perspective: Retrospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

Macrodissection of borderline ovarian tumor tissue. DNA extraction from paraffin embedded material for genetic analysis.

• Sampling Method: Probability Sample
• Study Population: Patients with proven serous bordeline ovarian tumors.
• Condition: Ovarian Neoplasm Epithelial

Intervention

Genetic: genomic mutations study

Sequencing of the DNA samples extracted from the subgroups

1. serous BOT tissue,
2. serous BOT tissue with non-invasive implants and
3. serous BOT tissue with micropapillary grow pattern will undergo a panel testing for Type 1 genes (small panel 15-40 mutations) AND p53 AND BRCA testing

Sequencing of the DNA samples extracted from the serous BOT tissue with invasive implants will undergo a more comprehensive examination (large panel +- 1000 genes checked)

Study Groups/Cohorts

• serous BOT
  simple serous BOT ovarian tissue
  Intervention: Genetic: genomic mutations study
• serous BOT with non-invasive implants
  BOT ovarian tissue presenting with non-invasive implants
  Intervention: Genetic: genomic mutations study
• sBOT with micropapillary grow pattern
  BOT ovarian tissue presenting with micropapillary grow pattern
  Intervention: Genetic: genomic mutations study
• serous BOT with invasive implants
  sBOT ovarian tissue presenting with invasive implants at the time of diagnosis
  Intervention: Genetic: genomic mutations study

Publications *

• Morice P, Uzan C, Fauvet R, Gouy S, Duvillard P, Darai E. Borderline ovarian tumour: pathological diagnostic dilemma and risk factors for invasive or lethal recurrence. Lancet Oncol. 2012 Mar;13(3):e103-15. doi: 10.1016/S1470-2045(11)70288-1.
• Vang R, Shih IeM, Kurman RJ. Ovarian low-grade and high-grade serous carcinoma: pathogenesis, clinicopathologic and molecular biologic features, and diagnostic problems. Adv Anat Pathol. 2009 Sep;16(5):267-82. doi: 10.1097/PAP.0b013e3181b4fffa.
• Despierre E, Lambrechts D, Neven P, Amant F, Lambrechts S, Vergote I. The molecular genetic basis of ovarian cancer and its roadmap towards a better treatment. Gynecol Oncol. 2010 May;117(2):358-65. doi: 10.1016/j.ygyno.2010.02.012. Epub 2010 Mar 7.
• Kurman RJ, Shih IeM. The origin and pathogenesis of epithelial ovarian cancer: a proposed unifying theory. Am J Surg Pathol. 2010 Mar;34(3):433-43. doi: 10.1097/PAS.0b013e3181cf3d79.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 19, 2019): 20
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: April 30, 2024
• Estimated Primary Completion Date: December 31, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Paraffin embedded material from the original borderline ovarian tumor must be present and of good quality for DNA extraction.
• Original slides are available for central pathological review.

Exclusion Criteria:

• Presence of invasive ovarian carcinoma.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Stefan Cosyns, Dr; 24776020 ext +32; scosyns@uzbrussel.be

• Listed Location Countries: Belgium

Administrative Information

• NCT Number: NCT03883542
• Other Study ID Numbers: sBOT
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Stefan Cosyns, Universitair Ziekenhuis Brussel
• Original Responsible Party: Same as current
• Current Study Sponsor: Universitair Ziekenhuis Brussel
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: stef cosyns, dr; UZBrussel

• PRS Account: Universitair Ziekenhuis Brussel
• Verification Date: May 2023