Prevalence of BRCA in Patients With Ovarian Cancer

• ClinicalTrials.gov Identifier: NCT02222883
• Recruitment Status: Completed
• First Posted: August 21, 2014
• Last Update Posted: June 16, 2021
• Sponsor: AGO Research GmbH
• Information provided by (Responsible Party): AGO Research GmbH

Tracking Information

• First Submitted Date: August 19, 2014
• First Posted Date: August 21, 2014
• Last Update Posted Date: June 16, 2021
• Actual Study Start Date: March 2015
• Actual Primary Completion Date: April 1, 2021 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: August 21, 2014): Germline alterations in BRCA1/2 (yes/no) and other ovarian cancer predisposing genes (yes/no; if yes which) [ Time Frame: once per sample ]
• Original Primary Outcome Measures (submitted: August 19, 2014): Evidence of germline alterations in BRCA1/2 and other ovarian cancer predisposing genes [ Time Frame: once per sample ]

Current Secondary Outcome Measures (submitted: June 11, 2021)

• Results of Immunohistochemistry in tumor samples [ Time Frame: once per sample ]
• Somatic alterations in BRCA1/2 (yes/no) and other ovarian cancer predisposing genes (yes/no; if yes which) [ Time Frame: once per sample ]
• BRCAness tumor phenotype in ovarian cancer (yes/no). [ Time Frame: once per sample ]
• Differences of tumor samples from primary and relapsed disease [ Time Frame: once per sample for each stage of disease ]
• Patient Survey for perspectives and satisfaction regarding testing and counseling [ Time Frame: once after BRCA result is available ]
  3 questions
• Determining the correlation of genetic alterations, cancer treatments, overall survival, progression-free survival and occurrence of new malignancies [ Time Frame: once ]

Original Secondary Outcome Measures (submitted: August 19, 2014)

• Immunohistochemistry and DNA extraction from tumor samples [ Time Frame: once per sample ]
• Evidence of somatic alterations in BRCA1/2 and other ovarian cancer predisposing genes [ Time Frame: once per sample ]
• Evidence for a BRCAness tumor phenotype in ovarian cancer. [ Time Frame: once per sample ]
• Differences of tumor samples from primary and relapsed disease [ Time Frame: once per sample for each stage of disease ]
• Evaluation of patient perspectives and satisfaction regarding testing and counseling (survey) [ Time Frame: once after BRCA result is available ]

Current Other Pre-specified Outcome Measures (submitted: June 11, 2021)

• Validate the results from Pennington et al. (Pennington et al. Clin Cancer Res 2014) [ Time Frame: once ]
• Evaluate predictive value of PARp-1 expression for HRD mutations [ Time Frame: once for all samples ]

Original Other Pre-specified Outcome Measures (submitted: August 19, 2014)

• Validate the results from Pennington et al. (Pennington et al. Clin Cancer Res 2014) [ Time Frame: once ]
• Evaluate predictive value of PARp-1 expression for HRD mutations [ Time Frame: once for all samples ]
• Identify BRCA1/2 promoter hypermethylation/epigenetic alterations in addition to genetic alterations. [ Time Frame: once for all samples ]
• Identify and characterize large rearrangements in BRCA1/2 with MLPA in the tumor tissue probes [ Time Frame: once for all samples ]

Descriptive Information

• Brief Title: Prevalence of BRCA in Patients With Ovarian Cancer
• Official Title: Prevalence of BRCA in Patients With Primary or Platinum Sensitive Recurrent Ovarian Cancer.
• Brief Summary: The aim of this prospective registration and translational research study is to evaluate the praevalence of BRCA regarding germline and somatic mutations.
• Detailed Description: Explorative analysis will be performed.
• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

EDTA Blood sample Tumorblock

• Sampling Method: Probability Sample
• Study Population: 500 consecutive patients (up to 250 patients with primary diagnosis and up to 250 patients with platinum-sensitive recurrence of ovarian cancer.

Condition

• BRCA Status
• Ovarian Cancer

• Intervention: Genetic: Testing of BRCA status regarding germline and somatic mutation

Study Groups/Cohorts

• patients with primary diagnosis
  patients with primary diagnosis of ovarian cancer for testing of BRCA status regarding germline and somatic mutation
  Intervention: Genetic: Testing of BRCA status regarding germline and somatic mutation
• patients with platinum-sensitive recurrence
  patients with platinum-sensitive recurrence of ovarian cancer for testing of BRCA status regarding germline and somatic mutation
  Intervention: Genetic: Testing of BRCA status regarding germline and somatic mutation

Publications *

• Schouten PC, Richters L, Vis DJ, Kommoss S, van Dijk E, Ernst C, Kluin RJC, Marmé F, Lips EH, Schmidt S, Scheerman E, Prieske K, van Deurzen CHM, Burges A, Ewing-Graham PC, Dietrich D, Jager A, de Gregorio N, Hauke J, du Bois A, Nederlof PM, Wessels LF, Hahnen E, Harter P, Linn SC, Schmutzler RK. Ovarian Cancer-Specific BRCA-like Copy-Number Aberration Classifiers Detect Mutations Associated with Homologous Recombination Deficiency in the AGO-TR1 Trial. Clin Cancer Res. 2021 Dec 1;27(23):6559-6569. doi: 10.1158/1078-0432.CCR-21-1673. Epub 2021 Sep 30.
• Hauke J, Harter P, Ernst C, Burges A, Schmidt S, Reuss A, Borde J, De Gregorio N, Dietrich D, El-Balat A, Kayali M, Gevensleben H, Hilpert F, Altmüller J, Heimbach A, Meier W, Schoemig-Markiefka B, Thiele H, Kimmig R, Nürnberg P, Kast K, Richters L, Sehouli J, Schmutzler RK, Hahnen E. Sensitivity and specificity of loss of heterozygosity analysis for the classification of rare germline variants in BRCA1/2: results of the observational AGO-TR1 study (NCT02222883). J Med Genet. 2022 Mar;59(3):248-252. doi: 10.1136/jmedgenet-2020-107353. Epub 2020 Dec 3.
• Hauke J, Hahnen E, Schneider S, Reuss A, Richters L, Kommoss S, Heimbach A, Marmé F, Schmidt S, Prieske K, Gevensleben H, Burges A, Borde J, De Gregorio N, Nürnberg P, El-Balat A, Thiele H, Hilpert F, Altmüller J, Meier W, Dietrich D, Kimmig R, Schoemig-Markiefka B, Kast K, Braicu E, Baumann K, Jackisch C, Park-Simon TW, Ernst C, Hanker L, Pfisterer J, Schnelzer A, du Bois A, Schmutzler RK, Harter P. Deleterious somatic variants in 473 consecutive individuals with ovarian cancer: results of the observational AGO-TR1 study (NCT02222883). J Med Genet. 2019 Sep;56(9):574-580. doi: 10.1136/jmedgenet-2018-105930. Epub 2019 Apr 12.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 25, 2015): 530
• Original Estimated Enrollment (submitted: August 19, 2014): 500
• Actual Study Completion Date: April 1, 2021
• Actual Primary Completion Date: April 1, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Female ovarian cancer patients aged >= 18 years.
• Women with first diagnosis of epithelial ovarian cancer OR women diagnosed with platinum-sensitive recurrent ovarian cancer.
• Multiple platinum based prior therapies are allowed.

Exclusion Criteria:

• Non-epithelial ovarian malignancy.
• Platinum-resistant or refractory disease.
• Paraffin embedded tumor samples not available.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany

Administrative Information

• NCT Number: NCT02222883
• Other Study ID Numbers: AGO-TR 1
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: AGO Research GmbH
• Original Responsible Party: Same as current
• Current Study Sponsor: AGO Research GmbH
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Philipp Harter, PhD MD; Kliniken Essen-Mitte, Germany

• PRS Account: AGO Research GmbH
• Verification Date: June 2021