Randomized CT to Evaluate Efficacy of Neoadjuvant Chemotherapy Customized by Levels of BRCA1-HER2 Negative Breast Cancer (BERNAQ)

March 9, 2017 updated by: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla

Randomized Open-label, Multicentric, Phase II Clinical Trial to Evaluate the Efficacy of a Neoadjuvant Chemotherapy Scheme Customized by Levels of BRCA1 in Women With Primary HER2 Negative Breast Cancer (The BERNAQ Clinical Trial)

Neoadjuvant chemotherapy (NAC) is increasingly used for early-stage operable breast cancer. Response of breast cancer to NAC is correlated with survival: patients who obtain greatest survival advantage are those who attain complete response of their primary tumor. BReast Cancer 1 (BRCA1) plays a crucial role in DNA repair and associations between BRCA1 mRNA expression and sensitivity to platinum and/or resistance to taxanes has been previously documented. We propose a two-arm, randomized, multi-centre, open-label phase II study to compare the efficacy and tolerability of NAC customized by BRCA 1 levels versus standard FEC chemotherapy, being pathological complete response the primary endpoint.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Neoadjuvant chemotherapy (NAC) is increasingly used for early-stage operable breast cancer. Response of breast cancer to NAC is correlated with survival: patients who obtain greatest survival advantage are those who attain complete response of their primary tumor.BReast Cancer 1 (BRCA1) plays a crucial role in DNA repair. Associations between BRCA1 mRNA expression and sensitivity to platinum and/or resistance to taxanes are previously documented. Improving complete response rates with NAC we can improve outcomes in breast cancer. If we establish biomarkers which predict better response we may optimized treatment by individualized breast cancer care. Therefore, we propose a two-arm, randomized, multi-centre, open-label phase II study. The study will compare the efficacy and tolerability of NAC customized by BRCA 1 levels versus standard chemotherapy, being pathological complete response the primary endpoint. Women with primary Her-2 negative breast cancer who have not undergone previous treatment for invasive breast cancer will be randomized to receive the following: Treatment Arm 1 (standard therapy): 5-Fluorouracil, Epirubicin and Cyclophosphamide day 1 every 3 weeks per three cycles; Treatment Arm 2: Patients with low levels of BRCA1 mRNA will receive Epirubicin and Cisplatin day 1 every 3 weeks and 5-Fluorouracil for three cycles; And patients with high levels of BRCA1 will receive docetaxel day 1 every three weeks per three cycles. Definitive surgery will be performed within 4 weeks after the last cycle.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Cádiz, Spain, 11009
        • Hospital Universitario Puerta del Mar
      • Córdoba, Spain, 14004
        • Hospital Universitario Reina Sofia
      • Huelva, Spain, 21005
        • Hospital Universitario Juan Ramón Jiménez
      • Jaén, Spain, 23007
        • Complejo Hospitalario de Jaén
      • Seville, Spain, 41007
        • Hospital Universitario Virgen Macarena
      • Seville, Spain, 41013
        • Hospital Universitario Virgen del Rocío
      • Seville, Spain, 41014
        • Hospital Universitario Nuestra Señora de Valme

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Female gender
  • 18 years or older
  • Performance Status- ECOG: 0-1
  • Histologically confirmed invasive breast cancer
  • Primary tumor greater than 2 cm diameter
  • Any N (0-3)
  • No evidence of metastasis (M0), HER-2/ERBb2 negative.
  • Known hormone receptors status.
  • Haematopoietic status: Absolute neutrophil count > 1.5 x 109/L; Platelet count > 100 x 109/L
  • Hemoglobin at least 9 g/dl)
  • Hepatic status: Serum total bilirubin < 1.5 x upper limit of normal (ULN), in the case of known Gilbert's syndrome, a higher serum total bilirubin (< 2 x ULN) is allowed;AST and ALT < 2.5 times ULN; Alkaline phosphatase < 2.5 times ULN)
  • Renal status: Creatinine < 1.5 mg/dl or Cl CR > 60 ml/m
  • For women of childbearing potential Negative serum pregnancy test, within 2-weeks (preferably 7 days) prior to randomization.
  • Signed informed consent form (ICF).

Exclusion Criteria:

  • Received any prior treatment for primary invasive breast cancer.
  • Previous (less than 10 years) or current history of malignant neoplasms, except for curatively treated:
  • Basal and squamous cell carcinoma of the skin;Carcinoma in situ of the cervix.
  • Diagnosis of inflammatory breast cancer.
  • Known history of uncontrolled or symptomatic angina, clinically significant arrhythmias, congestive heart failure, transmural myocardial infarction uncontrolled hypertension (? 180/110), unstable diabetes mellitus, dyspnoea at rest, or chronic therapy with oxygen.
  • Left Ventricular Ejection Fraction of < 50% measured by echocardiography.
  • Concurrent disease or condition that would make the subject inappropriate for study participation or any serious medical disorder that would interfere with the subject?s safety.
  • Unresolved or unstable, serious adverse events from prior administration of another investigational drug.
  • Active or uncontrolled infection.
  • Dementia, altered mental status, or any psychiatric condition that would prevent the understanding or rendering of ICF.
  • Concurrent neoadjuvant cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic therapy other than the trial therapies).
  • Concurrent treatment with an investigational agent or participation in another therapeutic clinical trial.
  • Known immediate or delayed hypersensitivity reaction, idiosyncrasy or contraindication to drugs chemically related to any of the study treatments or their excipients.
  • Pregnant or lactating women.
  • Refusal to use contraception throughout the study (surgical sterilization, barrier methods associated with spermicidal gels or total abstinence). Use of hormonal contraceptives is not allowed.
  • Patient unable to comply with study procedures.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Standard FEC Regimen
Epirubicin + Ciclofosfamide + Fluorouracil + Paclitaxel
Drug: Epirubicin + Ciclofosfamide + Fluorouracil + Paclitaxel
Epirubicin 90 mg/m2 + Ciclofosfamide 600 mg/m2 + 5-Fluorouracil 600 mg/m2 intravenous infusion on day 1 every three weeks, for four cycles; followed by Paclitaxel 100 mg/m2 weekly for eight weeks.
Other Names:
  • Standard FEC Regimen
Experimental: No or Low BRCA1 expression
Epirubicin + Cisplatin + Fluorouracil
Drug: Epirubicin + Cisplatin + Fluorouracil
Epirubicin 60 mg/m2 + Cisplatin 60 mg/m2 intravenous infusion on day 1 every three weeks and 5-Fluorouracil 200 mg/m2/day for eight cycles.
Other Names:
  • QT combination
Experimental: Normal or High BRCA1 expression
Docetaxel + Ciclofosfamide
Drug: Docetaxel + Ciclofosfamide
Docetaxel 75 mg/m2 + Ciclofosfamide 600 mg/m2, intravenous infusion on day 1 every three weeks, for eight cycles.
Other Names:
  • QT combination

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Rate of residual tumor types RCB-0 and RCB-I (good pathological response) at the time of surgery.
Time Frame: 4-8 weeks after the last neoadjuvant chemotherapy cycle.
To evaluate and compare the rate of good pathological response (residual tumor types RCB-0 and RCB-I) at the time of surgery in patients with ER or PgR positive, or triple negative (non-Her2/Erb 2 overexpressing and/or amplified) breast cancer randomized to standard neoadjuvant chemotherapy (NAC) based in anthracyclines versus customized NAC according levels of BRCA1 expression.
4-8 weeks after the last neoadjuvant chemotherapy cycle.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Percentaje of patients candidates to conventional mastectomy as indicated by surgeon
Time Frame: At baseline and after the last neoadjuvant chemotherapy cycle (up to 24 weeks after randomization).
At baseline and after the last neoadjuvant chemotherapy cycle (up to 24 weeks after randomization).
Rates of residual tumor types RCB-0, RCB-I, RCB-II and RCB-III pathological response in surgical breast and axillary node resection specimens
Time Frame: 4-8 weeks after the last neoadjuvant chemotherapy cycle .
4-8 weeks after the last neoadjuvant chemotherapy cycle .
Percentage of patients with negative axillary nodes
Time Frame: 4-8 weeks after the last neoadjuvant chemotherapy cycle.
4-8 weeks after the last neoadjuvant chemotherapy cycle.
Complete tumoral response at the time of surgery (WHO criteria).
Time Frame: At baseline and after the last neoadjuvant chemotherapy cycle (up to 24 weeks after randomization).
At baseline and after the last neoadjuvant chemotherapy cycle (up to 24 weeks after randomization).
Percentaje of patients candidates to breast conserving mastectomy as indicated by surgeon
Time Frame: At baseline and after the last neoadjuvant chemotherapy cycle (up to 24 weeks after randomization).
At baseline and after the last neoadjuvant chemotherapy cycle (up to 24 weeks after randomization).
Partial tumoral response at the time of surgery (WHO criteria).
Time Frame: At baseline and after the last neoadjuvant chemotherapy cycle (up to 24 weeks after randomization).
At baseline and after the last neoadjuvant chemotherapy cycle (up to 24 weeks after randomization).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Fundación Pública Andaluza para la gestión de la Investigación en Sevilla

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Manuel Ruiz-Borrego, MD, University Hospital Virgen del Rocio

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 10, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 10, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 30, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 11, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 19, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 13, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 9, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2011-005843-28

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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