Breast CancerPhase 2BERNAQNCT02365805
Randomized CT to Evaluate Efficacy of Neoadjuvant Chemotherapy Customized by Levels of BRCA1-HER2 Negative Breast Cancer
A Phase 2 study testing Epirubicin + Ciclofosfamide + Fluorouracil + Paclitaxel, Epirubicin + Cisplatin + Fluorouracil and Docetaxel + Ciclofosfamide in people with Breast Cancer, run by Fundación Pública Andaluza para la gestión de la Investigación en Sevilla at 7 sites in Spain.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Epirubicin + Ciclofosfamide + Fluorouracil + Paclitaxel, Epirubicin + Cisplatin + Fluorouracil and Docetaxel + Ciclofosfamide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 7 sitesSpain
- Study dates
- Apr 2014to 10 Oct 2016
- Phase
- Phase 2
- 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 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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).
Who cannot join
- 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.
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- 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.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
Spain7 sites
Hospital Universitario Puerta del Mar
Cadiz, Cádiz, 11009
Hospital Universitario Reina Sofía
Córdoba, Córdoba, 14004
Hospital Universitario Juan Ramón Jimenez
Huelva, Huelva, 21005
Complejo Hospitalario de Jaén
Jaén, Jaén, 23007
Hospital Universitario Virgen Macarena
Seville, Seville, 41007
Hospital Universitario Virgen del Rocío
Seville, Seville, 41013
Hospital Universitario Nuestra Señora de Valme
Seville, Seville, 41014
About this study
Official title: 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.
Read the 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.
- Conditions
- Breast Cancer
- Being tested
- Epirubicin + Ciclofosfamide + Fluorouracil + Paclitaxel, Epirubicin + Cisplatin + Fluorouracil, Docetaxel + Ciclofosfamide
- Keywords
- BRCA 1 levels, HER2 Negative
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Epirubicin + Ciclofosfamide + Fluorouracil + PaclitaxelDrug
Also called Standard FEC Regimen
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.
Epirubicin + Cisplatin + FluorouracilDrug
Also called QT combination
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.
Docetaxel + CiclofosfamideDrug
Also called QT combination
Docetaxel 75 mg/m2 + Ciclofosfamide 600 mg/m2, intravenous infusion on day 1 every three weeks, for eight cycles.
| Study group | Role | What they receive |
|---|---|---|
| Standard FEC Regimen | Active comparator | Epirubicin + Ciclofosfamide + Fluorouracil + Paclitaxel Receives: Drug: Epirubicin + Ciclofosfamide + Fluorouracil + Paclitaxel |
| No or Low BRCA1 expression | Experimental | Epirubicin + Cisplatin + Fluorouracil Receives: Drug: Epirubicin + Cisplatin + Fluorouracil |
| Normal or High BRCA1 expression | Experimental | Docetaxel + Ciclofosfamide Receives: Drug: Docetaxel + Ciclofosfamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of residual tumor types RCB-0 and RCB-I (good pathological response) at the time of surgery.
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.
Measured: 4-8 weeks after the last neoadjuvant chemotherapy cycle.
Secondary outcomes (6)
Percentaje of patients candidates to conventional mastectomy as indicated by surgeon
Measured: 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
Measured: 4-8 weeks after the last neoadjuvant chemotherapy cycle .
Percentage of patients with negative axillary nodes
Measured: 4-8 weeks after the last neoadjuvant chemotherapy cycle.
Complete tumoral response at the time of surgery (WHO criteria).
Measured: 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
Measured: 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).
Measured: At baseline and after the last neoadjuvant chemotherapy cycle (up to 24 weeks after randomization).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2015 (estimated)
- Study startApr 2014
- Primary completion10 Oct 2016
- Study completion10 Oct 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Manuel Ruiz-Borrego, MD, Principal investigator, University Hospital Virgen del Rocío
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02365805
- Sponsor's protocol ID
- 2011-005843-28
- Acronym
- BERNAQ
- Status last verified
- Mar 2017
- First submitted
- 30 Dec 2014
- Last updated
- 13 Mar 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT02365805
- Acronym / sponsor ID
- BERNAQ / 2011-005843-28
- Conditions
- Breast Cancer
- Keywords
- BRCA 1 levels, HER2 Negative
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Fundación Pública Andaluza para la gestión de la Investigación en SevillaUniversity, hospital or other
- Study start
- Apr 2014
- Primary completion
- 10 Oct 2016 (actual)
- Study completion
- 10 Oct 2016 (actual)
- First posted
- 19 Feb 2015 (estimated)
- 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.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Standard FEC Regimen | Active comparator | Drug: Epirubicin + Ciclofosfamide + Fluorouracil + PaclitaxelEpirubicin + Ciclofosfamide + Fluorouracil + Paclitaxel |
| No or Low BRCA1 expression | Experimental | Drug: Epirubicin + Cisplatin + FluorouracilEpirubicin + Cisplatin + Fluorouracil |
| Normal or High BRCA1 expression | Experimental | Drug: Docetaxel + CiclofosfamideDocetaxel + Ciclofosfamide |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Female gender
- 18 years or older
- Performance Status- ECOG: 0-1
- Histologically confirmed invasive breast cancer
- Primary tumor greater than 2 cm diameter
Key exclusion criteria (16 listed)
- 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.
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 |
|---|---|---|
| Epirubicin + Ciclofosfamide + Fluorouracil + PaclitaxelAlso: Standard FEC RegimenEpirubicin 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. | Drug | Standard FEC Regimen |
| Epirubicin + Cisplatin + FluorouracilAlso: QT combinationEpirubicin 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. | Drug | No or Low BRCA1 expression |
| Docetaxel + CiclofosfamideAlso: QT combinationDocetaxel 75 mg/m2 + Ciclofosfamide 600 mg/m2, intravenous infusion on day 1 every three weeks, for eight cycles. | Drug | Normal or High BRCA1 expression |
Primary outcome
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.
6 secondary outcomes
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).
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 .
Percentage of patients with negative axillary nodes
Time frame: 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).
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).
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).
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 13 Mar 2017.
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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.
Manuel Ruiz-Borrego, MD principal investigator
University Hospital Virgen del Rocío
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Epirubicin + Ciclofosfamide + Fluorouracil + Paclitaxel, Epirubicin + Cisplatin + Fluorouracil and Docetaxel + Ciclofosfamide in people with Breast Cancer, run by Fundación Pública Andaluza para la gestión de la Investigación en Sevilla at 7 sites in Spain.
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 14 inclusion and 16 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 13 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Spain. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
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.). 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 13 Mar 2017.