Triple Negative Breast NeoplasmsTNBCbrazilNCT03539965
Triple-negative Breast Cancer: a New Perspective on Biomarkers
An observational study of Triple Negative Breast Neoplasms and Triple Negative Breast Cancer, run by Instituto Nacional de Cancer, Brazil at 1 site in Brazil.
Trial summary
A single-institutional cohort to determine the prevalence of new immunohistochemical panel in advanced triple-negative submitted to neoadjuvant chemotherapy and its association with response and survival. Read more about this study
- Who is it for?
- Ages 18 to 80 years, women only
- Conditions the study is for
- Triple Negative Breast Neoplasms, Triple Negative Breast Cancer
- How many people
- 239 participants
- Where
- 1 siteBrazil
- Study dates
- 1 Jan 2010to 31 Dec 2014
- 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: Women who is biopsied and diagnosed with breast cancer in the public health system is referred to Brazilian National Cancer Institute (INCA) through a registry and screening performed by the Municipal Health Department of the city of Rio de Janeiro. Therefore, it becomes a great field for research of cancer patients by the large number of cases. Absolutely all patients enrolled in INCA for treatment have their biopsy material reviewed in DIPAT. In this cohort, will be studied women with locally advanced TNBC consecutively enrolled at INCA between January 2010 and December 2014 that were submitted to neoadjuvant chemotherapy and subsequently operated.
Who may be able to join
- Women older than 18 years
- Locally advanced TNBC (T3-4, any Node, M0; any Tumor, N1-3, M0)
- Patients submitted to anthracycline and taxane-based neoadjuvant chemotherapy and then operated between January 2010 and December 2014 at the Brazilian National Cancer Institute.
Who cannot join
- Patients with metastatic Breast Cancer;
- Other non-epithelial histologies of breast cancer;
- Pure Ductal Carcinoma In Situ diagnoses are not eligible.
- Patients with scarce material for immunohistochemistry;
- Other primary synchronous or anachronistic tumors in the breast or other sites;
- No prior immunotherapeutic, chemotherapeutic or antiandrogenic drugs allowed
- Patients treated with alternative neoadjuvant chemotherapy regimens (not based on anthracycline and taxane) or with only hormone therapy;
- Patients who received chemotherapy or who were operated outside the INCA.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Triple-negative Breast Cancer: a New Perspective on Predictive and Prognostic Biomarkers
A single-institutional cohort to determine the prevalence of new immunohistochemical panel in advanced triple-negative submitted to neoadjuvant chemotherapy and its association with response and survival.
Read the detailed description
Background/Rationale: Triple negative breast cancer (TNBC) is known to be a heterogeneous disease, and different molecular sub-classifications are proposed based in specific biomarkers as immunohistochemical (IHC) expression of the androgen-receptor (AR), Epidermal growth Factor Receptor (EGFR), Cytokeratin 5/6 (CK5/6), Cytokeratin14 (CK14), Cytokeratin 17 (CK17), clusters of differentiation 117 (CD 117), p53, Ki67 level, Programmed cell death-ligand 1 (PD-L1) and PD-L2 in tumor cell membrane and the pattern of tumor infiltrating mono-lymphocytes (PD-1+, FOXP3+, CD 4+ or cluster designation 8 (CD8 +), CD 3+, cluster of differentiation 56 (CD56+), cluster designation 68 (CD68+) or CD 14+). Predicting response and survival to neoadjuvant treatment of locally advanced triple-negative breast cancer remains a major challenge. Many doubts still prevail over the role of new biomarkers in predicting different outcomes for tumors with the same stage and morphological characteristics.
Objectives and Hypotheses:
Primary objective: To evaluate the association of the intratumoral lymphocytic infiltrate (TILs) status profile in the core biopsy with complete pathological response (CPR) outcomes to neoadjuvant chemotherapy and progression-free survival (PFS). Secondary objectives: To evaluate the association of the others biomarkers expression profile and the quality of TILs with PFS and CPR. To determine the prevalence of a large immunohistochemical panel (AR, EGFR, CK5/6, CK14, CK17, CD 117, p53, Ki67 level, PD-L1 and PD-L2 in tumor cell membrane and the pattern of tumor infiltrating mono-lymphocytes PD-1+, FOXP3+, CD 4+ , CD8 +, CD 3+, CD56+, CD68+ and/or CD 14+), before and after neoadjuvant chemotherapy. To determine if the negativation of biomarkers after the systemic treatment is associated with CPR and PFS.
Methods:
Study design: A cohort with retrospective data collection and sectional analysis of pathological material.
Data Source(s): Medical records and pathological material. Study Population: Women with locally advanced triple negative breast cancer consecutively enrolled at Brazilian National Cancer Institute (INCA) submitted to neoadjuvant treatment and subsequently operated.
Exposure(s): Status of specified biomarkers. Outcome(s): Complete Pathologic Response and Progression free Survival and Sample Size Estimations: With a type I error of 5% and study power of 80%, it is estimated that 155 patients are needed.
Statistical Analysis: Statistical analysis will be performed using SPSS (version 18.0 for windows, statistical package for social science (SPSS) Inc., Chicago, IL). Survival curves will be constructed using the Kaplan-Meier method.
- Keywords
- Neoadjuvant Chemotherapy, Predictive Biomarkers, Prognostic Biomarkers, Complete Pathological Response, Tumor Infiltrating Lymphocytes, PD-L1, PD-L2
- Medical subject headings
- Triple Negative Breast Neoplasms, Pathologic Complete Response
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Single-arm cohort | Initially, patients will be analyzed in a single group. After determining the status of the biomarkers, the patient sample will be divided into specific groups for comparative purposes. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival (PFS)
The first event defined as local recurrence or distant relapse, or death, whichever come first.
Measured: Approximately 24 months: from diagnosis up to the first event defined as local recurrence or distant relapse, or death, whichever come first through study completion.
Secondary outcomes (4)
Clinical Response Rate
To determine the clinical response rate in patients with palpable disease.
Measured: From date of first cycle of chemotherapy until completion of neoadjuvant treatment, approximately 16 weeks
Objective response rate
To compare overall objective response rate in both treatment groups.
Measured: From date of first cycle of chemotherapy until completion of neoadjuvant treatment, approximately 16 weeks
Determine predictive markers
To determine predictive markers for sensitivity and resistance to chemotherapy.
Measured: Approximately 24 weeks: from diagnosis up to surgery.
Determine prognostic markers
To determine prognostic markers for progression free survival after neoadjuvant chemotherapy and surgery.
Measured: Approximately 24 months: from diagnosis up to the first event defined as local recurrence or distant relapse, or death, whichever come first through study completion.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2018
- Study start1 Jan 2010
- Primary completion31 Dec 2014
- Study completion31 Dec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Triple Negative Breast NeoplasmsStudies 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
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 239 participants (actual)
Sponsor and investigators
- Lead sponsor
- Instituto Nacional de Cancer, Brazil
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Jesse Lopes da Silva, Instituto Nacional de Cancer, Brazil
- Investigators
- Jesse L da Silva, MD, Principal investigator, Instituto Nacional de Cancer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03539965
- Sponsor's protocol ID
- TNBCbrazil
- Acronym
- TNBCbrazil
- Status last verified
- May 2018
- First submitted
- 4 May 2018
- Last updated
- 31 May 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Triple-negative Breast Cancer: a New Perspective on Predictive and Prognostic Biomarkers
- ClinicalTrials.gov ID
- NCT03539965
- Acronym / sponsor ID
- TNBCbrazil / TNBCbrazil
- Keywords
- Neoadjuvant Chemotherapy, Predictive Biomarkers, Prognostic Biomarkers, Complete Pathological Response, Tumor Infiltrating Lymphocytes, PD-L1, PD-L2
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 239 participants (actual)
- Lead sponsor
- Instituto Nacional de Cancer, BrazilOther government
- Study start
- 1 Jan 2010 (actual)
- Primary completion
- 31 Dec 2014 (actual)
- Study completion
- 31 Dec 2014 (actual)
- First posted
- 30 May 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.
A single-institutional cohort to determine the prevalence of new immunohistochemical panel in advanced triple-negative submitted to neoadjuvant chemotherapy and its association with response and survival.
Detailed description
Background/Rationale: Triple negative breast cancer (TNBC) is known to be a heterogeneous disease, and different molecular sub-classifications are proposed based in specific biomarkers as immunohistochemical (IHC) expression of the androgen-receptor (AR), Epidermal growth Factor Receptor (EGFR), Cytokeratin 5/6 (CK5/6), Cytokeratin14 (CK14), Cytokeratin 17 (CK17), clusters of differentiation 117 (CD 117), p53, Ki67 level, Programmed cell death-ligand 1 (PD-L1) and PD-L2 in tumor cell membrane and the pattern of tumor infiltrating mono-lymphocytes (PD-1+, FOXP3+, CD 4+ or cluster designation 8 (CD8 +), CD 3+, cluster of differentiation 56 (CD56+), cluster designation 68 (CD68+) or CD 14+). Predicting response and survival to neoadjuvant treatment of locally advanced triple-negative breast cancer remains a major challenge. Many doubts still prevail over the role of new biomarkers in predicting different outcomes for tumors with the same stage and morphological characteristics.
Objectives and Hypotheses:
Primary objective: To evaluate the association of the intratumoral lymphocytic infiltrate (TILs) status profile in the core biopsy with complete pathological response (CPR) outcomes to neoadjuvant chemotherapy and progression-free survival (PFS). Secondary objectives: To evaluate the association of the others biomarkers expression profile and the quality of TILs with PFS and CPR. To determine the prevalence of a large immunohistochemical panel (AR, EGFR, CK5/6, CK14, CK17, CD 117, p53, Ki67 level, PD-L1 and PD-L2 in tumor cell membrane and the pattern of tumor infiltrating mono-lymphocytes PD-1+, FOXP3+, CD 4+ , CD8 +, CD 3+, CD56+, CD68+ and/or CD 14+), before and after neoadjuvant chemotherapy. To determine if the negativation of biomarkers after the systemic treatment is associated with CPR and PFS.
Methods:
Study design: A cohort with retrospective data collection and sectional analysis of pathological material.
Data Source(s): Medical records and pathological material. Study Population: Women with locally advanced triple negative breast cancer consecutively enrolled at Brazilian National Cancer Institute (INCA) submitted to neoadjuvant treatment and subsequently operated.
Exposure(s): Status of specified biomarkers. Outcome(s): Complete Pathologic Response and Progression free Survival and Sample Size Estimations: With a type I error of 5% and study power of 80%, it is estimated that 155 patients are needed.
Statistical Analysis: Statistical analysis will be performed using SPSS (version 18.0 for windows, statistical package for social science (SPSS) Inc., Chicago, IL). Survival curves will be constructed using the Kaplan-Meier method.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single-arm cohort | – | –Initially, patients will be analyzed in a single group. After determining the status of the biomarkers, the patient sample will be divided into specific groups for comparative purposes. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Women who is biopsied and diagnosed with breast cancer in the public health system is referred to Brazilian National Cancer Institute (INCA) through a registry and screening performed by the Municipal Health Department of the city of Rio de Janeiro. Therefore, it becomes a great field for research of cancer patients by the large number of cases. Absolutely all patients enrolled in INCA for treatment have their biopsy material reviewed in DIPAT. In this cohort, will be studied women with locally advanced TNBC consecutively enrolled at INCA between January 2010 and December 2014 that were submitted to neoadjuvant chemotherapy and subsequently operated.
Key inclusion criteria (3 listed)
- Women older than 18 years
- Locally advanced TNBC (T3-4, any Node, M0; any Tumor, N1-3, M0)
- Patients submitted to anthracycline and taxane-based neoadjuvant chemotherapy and then operated between January 2010 and December 2014 at the Brazilian National Cancer Institute.
Key exclusion criteria (8 listed)
- Patients with metastatic Breast Cancer;
- Other non-epithelial histologies of breast cancer;
- Pure Ductal Carcinoma In Situ diagnoses are not eligible.
- Patients with scarce material for immunohistochemistry;
- Other primary synchronous or anachronistic tumors in the breast or other sites;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Progression Free Survival (PFS)
Time frame: Approximately 24 months: from diagnosis up to the first event defined as local recurrence or distant relapse, or death, whichever come first through study completion.
The first event defined as local recurrence or distant relapse, or death, whichever come first.
4 secondary outcomes
Clinical Response Rate
Time frame: From date of first cycle of chemotherapy until completion of neoadjuvant treatment, approximately 16 weeks
Objective response rate
Time frame: From date of first cycle of chemotherapy until completion of neoadjuvant treatment, approximately 16 weeks
Determine predictive markers
Time frame: Approximately 24 weeks: from diagnosis up to surgery.
Determine prognostic markers
Time frame: Approximately 24 months: from diagnosis up to the first event defined as local recurrence or distant relapse, or death, whichever come first through study completion.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 May 2018.
- Individual participant dataSharing planned: No
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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.
Jesse L da Silva, MD principal investigator
Instituto Nacional de Cancer
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 Triple Negative Breast Neoplasms and Triple Negative Breast Cancer, run by Instituto Nacional de Cancer, Brazil at 1 site in Brazil.
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 3 inclusion and 8 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: finished, as of the sponsor's last update on 31 May 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 Brazil. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression Free Survival (PFS) (time frame: Approximately 24 months: from diagnosis up to the first event defined as local recurrence or distant relapse, or death, whichever come first through study completion.). 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 31 May 2018.