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Study Estimating Association Between Germline Mutations and PD-L1 Expression in Breast Cancer

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ClinicalTrials.gov Identifier: NCT03495544
Recruitment Status : Unknown
Verified April 2018 by Tatarstan Cancer Center.
Recruitment status was:  Recruiting
First Posted : April 12, 2018
Last Update Posted : April 12, 2018
Sponsor:
Information provided by (Responsible Party):
Tatarstan Cancer Center

Tracking Information
First Submitted Date March 15, 2018
First Posted Date April 12, 2018
Last Update Posted Date April 12, 2018
Actual Study Start Date January 1, 2018
Estimated Primary Completion Date March 17, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: April 4, 2018)
Diagnostic performance of PD-L1 expression in breast cancer [ Time Frame: January 2018-January 2019 ]
Number of samples of PD-L1 high expression in tumor and immune cells in FFPE breast tumor tissue and number of samples of PD-L1 low expression in tumor and immune cells in FFPE breast tumor tissue . The report will be represented as "PD-L1 high" or "PD-L1 low".
Original Primary Outcome Measures Same as current
Change History No Changes Posted
Current Secondary Outcome Measures
 (submitted: April 4, 2018)
  • Diagnostic performance of inherited gene mutations in breast cancer [ Time Frame: January 2018-January 2019 ]
    Mutations will be determined by "pathogenic" and "non pathogenic". Number of samples with "pathogenic" and "non pathogenic" mutations .
  • Association between germline DNA-repair genes mutations and PD-L1 expression level in in breast cancer [ Time Frame: January 2018-January 2019 ]
    To reveal the differences (percentages) of PD-L1 high tumor rate between patients with hereditary BC ( pathogenic mutations) who have clinically significant germline mutations in DNA-repair genes (HR- deficiency) and patients with sporadic BC without such mutations (non pathogenic mutations).
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Study Estimating Association Between Germline Mutations and PD-L1 Expression in Breast Cancer
Official Title Comparative, Multicenter Study Estimating Association Between Germline DNA-repair Genes Mutations and PD-L1 Expression Level in Breast Cancer
Brief Summary This is a multicentre, non-interventional, prospective study to be carried out in representative oncology departments / institutions in order to determine the association between the presence of germline DNA-repair genes mutations and PD-L1 expression level in tumour and immune cells in breast cancer. No additional procedures besides those already used in the routine clinical practice will be applied to the patients.
Detailed Description

Breast cancer (BC) occupies the first place among malignancy in females (29.9% of all tumors in female patients in Russian Federation in 2015) [1].

One of the most perspective direction of the oncotherapy is anticancer immunotherapy - employment of inhibitors of immune checkpoints. Immune checkpoints inhibitors (such as anti-PD-1 and anti-PD-L1 antibodies) have shown good clinical efficiency in clinical research to cure such malignant tumor with high mutation load, as melanoma, lung cancer, and others.

One of the hypothesis of such effect states that, usually, more cancer neoantigens are synthetized in the tumors with high mutation load (driven by genome instability), causing severe lymphoid infiltration [2-3]. This situation is balanced by overexpression of such inhibitors of the immune response as PD-1 and PD-L1 [4 - 6].

Breast cancer - is relatively heterogenic tumor, with different genetic, morphological and phenotypic forms.

Despite relatively low expression of PD-L1 in BC in general, there are reasons to believe that genetic instability, driven by mutations in genes involved in DNA repair, can increase the immunogenicity and, thus, the expression of PD-L1 in BC.

To date, it is widely accepted that 5-10% of BC cases are represented by hereditary types, i.e. mediated by germline pathogenic mutations in genes of DNA reparation pathways. Hereditary breast cancer (HBC), as well as ovarian cancer (OC), сaused by mutations in genes BRCA1, BRCA2, CHEK2, TP53 и PTEN, and others. Thus, one of the promising directions here is to understand the inter-relation among germline pathogenic mutations associated with HBC, and activity of PD-L1. It would allow to optimize selection of anti-PD-L1 therapy, by forming group of patients (matching criteria of HBC) with high level of PD-L1 expression in cancer cells and tumor-infiltrating lymphocytes.

Study Type Observational
Study Design Observational Model: Case-Control
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Probability Sample
Study Population patients, female aged between 18-80yrs with breast cancer
Condition Hereditary Breast Cancer
Intervention Diagnostic Test: PD-L1 expression
IHC testing of PD-L1 expression level in tumor tissue samples
Study Groups/Cohorts
  • Hereditary BC
    Pathogenic germline mutations in DNA-repair genes (TP53 MLH1 MSH2 MSH6 PMS2 EPCAM APC MUTYH CDKN2A CDK4 ATM KIT PDGFRA CDH1 CTNNA1 PRSS1 SPINK1 BRCA1 BRCA2 FANCI FANCL PALB2 RAD51B RAD51C RAD54L RAD51D CHEK1 CHEK2 CDK12 BRIP1 PPP2R2A BARD1 PARP1 STK11 XRCC3)
    Intervention: Diagnostic Test: PD-L1 expression
  • Sporadic BC
    Without germline mutations in DNA-repair genes (TP53 MLH1 MSH2 MSH6 PMS2 EPCAM APC MUTYH CDKN2A CDK4 ATM KIT PDGFRA CDH1 CTNNA1 PRSS1 SPINK1 BRCA1 BRCA2 FANCI FANCL PALB2 RAD51B RAD51C RAD54L RAD51D CHEK1 CHEK2 CDK12 BRIP1 PPP2R2A BARD1 PARP1 STK11 XRCC3)
    Intervention: Diagnostic Test: PD-L1 expression
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Unknown status
Estimated Enrollment
 (submitted: April 4, 2018)
390
Original Estimated Enrollment Same as current
Estimated Study Completion Date July 1, 2019
Estimated Primary Completion Date March 17, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • 1. The voluntary obtained informed consent signed by both the subject and the investigator.

    2. Females 18 years age or more. 3. Histologically confirmed BC with known hormone receptors and HER2neu receptors status, Grade of tumor, diagnosed before enrolment into the study.

    4. Availability of FFPE tissue samples received prior to any type of antitumor treatment start. Tumour tissue samples must be satisfied IHC requirements for PD-L1 testing.

    5. Ability of blood samples receiving for NGS germline mutations testing. 6. Completed medical records (stage, receptors status, demographic data)

Exclusion Criteria:

  • Any evidence of uncontrolled system pathology, active infections, active bleeding diathesis, renal graft, including virus hepatitis B, C or HIV.
Sex/Gender
Sexes Eligible for Study: Female
Ages 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries Russian Federation
Removed Location Countries  
 
Administrative Information
NCT Number NCT03495544
Other Study ID Numbers ESR-17-12934
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: Yes
Supporting Materials: Study Protocol
Responsible Party Tatarstan Cancer Center
Study Sponsor Tatarstan Cancer Center
Collaborators Not Provided
Investigators Not Provided
PRS Account Tatarstan Cancer Center
Verification Date April 2018