Hereditary Breast CancerNCT03495544
Study Estimating Association Between Germline Mutations and PD-L1 Expression in Breast Cancer
An observational study of Hereditary Breast Cancer, run by Tatarstan Cancer Center at 1 site in Russia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years, women only
- Conditions the study is for
- Hereditary Breast Cancer
- What is being tested?
- PD-L1 expression
- How many people
- 390 participants
- Where
- 1 siteRussia
- Study dates
- 1 Jan 2018to 1 Jul 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- Women only
- No healthy volunteers
- Adult, Older adult
Study population: patients, female aged between 18-80yrs with breast cancer
Who may be able to join
- 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)
Who cannot join
- Any evidence of uncontrolled system pathology, active infections, active bleeding diathesis, renal graft, including virus hepatitis B, C or HIV.
Trial locations and contacts
1 site in 1 country.
Russia1 site, 1 recruiting
- Recruiting
Tatarstan Cancer Cente
Kazan', Tatarstan Republic, 420029
Marat Gordiev, +79172399490, marat7925@gmail.com
Dina Sakaeva, +79033115085, d_sakaeva@mail.ru
About this study
Official title: Comparative, Multicenter Study Estimating Association Between Germline DNA-repair Genes Mutations and PD-L1 Expression Level in Breast Cancer
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.
Read the 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.
- Conditions
- Hereditary Breast Cancer
- Being tested
- PD-L1 expression
- Medical subject headings
- Breast Cancer, Familial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PD-L1 expressionDiagnostic test
IHC testing of PD-L1 expression level in tumor tissue samples
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: 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) Receives: Diagnostic Test: PD-L1 expression |
What is being measured
The primary outcome is the main question the study is designed to answer.
Diagnostic performance of PD-L1 expression in breast cancer
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".
Measured: January 2018-January 2019
Secondary outcomes (2)
Diagnostic performance of inherited gene mutations in breast cancer
Mutations will be determined by "pathogenic" and "non pathogenic". Number of samples with "pathogenic" and "non pathogenic" mutations .
Measured: January 2018-January 2019
Association between germline DNA-repair genes mutations and PD-L1 expression level in in breast cancer
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).
Measured: January 2018-January 2019
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2018
- Study start1 Jan 2018
- Primary completion17 Mar 2019 (estimated)
- Study completion1 Jul 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hereditary Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 390 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tatarstan Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03495544
- Sponsor's protocol ID
- ESR-17-12934
- Status last verified
- Apr 2018
- First submitted
- 15 Mar 2018
- Last updated
- 12 Apr 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparative, Multicenter Study Estimating Association Between Germline DNA-repair Genes Mutations and PD-L1 Expression Level in Breast Cancer
- ClinicalTrials.gov ID
- NCT03495544
- Acronym / sponsor ID
- ESR-17-12934
- Conditions
- Hereditary Breast Cancer
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 390 participants (estimated)
- Lead sponsor
- Tatarstan Cancer CenterUniversity, hospital or other
- Study start
- 1 Jan 2018 (actual)
- Primary completion
- 17 Mar 2019 (estimated)
- Study completion
- 1 Jul 2019 (estimated)
- First posted
- 12 Apr 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Hereditary BC | – | Diagnostic Test: PD-L1 expressionPathogenic 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) |
| Sporadic BC | – | Diagnostic Test: PD-L1 expressionWithout 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) |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- patients, female aged between 18-80yrs with breast cancer
Key inclusion criteria (4 listed)
- 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)
Key exclusion criteria (1 listed)
- Any evidence of uncontrolled system pathology, active infections, active bleeding diathesis, renal graft, including virus hepatitis B, C or HIV.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PD-L1 expressionIHC testing of PD-L1 expression level in tumor tissue samples | Diagnostic test | Hereditary BC, Sporadic BC |
Primary outcome
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".
2 secondary outcomes
Diagnostic performance of inherited gene mutations in breast cancer
Time frame: January 2018-January 2019
Association between germline DNA-repair genes mutations and PD-L1 expression level in in breast cancer
Time frame: January 2018-January 2019
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Apr 2018.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hereditary Breast Cancer, run by Tatarstan Cancer Center at 1 site in Russia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 12 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Marat Gordiev (+79172399490, marat7925@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Diagnostic performance of PD-L1 expression in breast cancer (time frame: January 2018-January 2019). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Apr 2018.