Randomized CT to Evaluate Efficacy of Neoadjuvant Chemotherapy Customized by Levels of BRCA1-HER2 Negative Breast Cancer
BERNAQ
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)
1 other identifier
interventional
30
1 country
7
Brief 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. 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2 breast-cancer
Started Apr 2014
7 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
April 1, 2014
CompletedFirst Submitted
Initial submission to the registry
December 30, 2014
CompletedFirst Posted
Study publicly available on registry
February 19, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 10, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
October 10, 2016
CompletedMarch 13, 2017
March 1, 2017
2.5 years
December 30, 2014
March 9, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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.
4-8 weeks after the last neoadjuvant chemotherapy cycle.
Secondary Outcomes (6)
Percentaje of patients candidates to conventional mastectomy as indicated by surgeon
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
4-8 weeks after the last neoadjuvant chemotherapy cycle .
Percentage of patients with negative axillary nodes
4-8 weeks after the last neoadjuvant chemotherapy cycle.
Complete tumoral response at the time of surgery (WHO criteria).
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
At baseline and after the last neoadjuvant chemotherapy cycle (up to 24 weeks after randomization).
- +1 more secondary outcomes
Study Arms (3)
Standard FEC Regimen
ACTIVE COMPARATOREpirubicin + Ciclofosfamide + Fluorouracil + Paclitaxel
No or Low BRCA1 expression
EXPERIMENTALEpirubicin + Cisplatin + Fluorouracil
Normal or High BRCA1 expression
EXPERIMENTALDocetaxel + Ciclofosfamide
Interventions
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 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 75 mg/m2 + Ciclofosfamide 600 mg/m2, intravenous infusion on day 1 every three weeks, for eight cycles.
Eligibility Criteria
You may qualify if:
- Female gender
- 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).
You may not qualify if:
- 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.
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (7)
Hospital Universitario Puerta del Mar
Cadiz, Cádiz, 11009, Spain
Hospital Universitario Reina Sofía
Córdoba, Córdoba, 14004, Spain
Hospital Universitario Juan Ramón Jimenez
Huelva, Huelva, 21005, Spain
Complejo Hospitalario de Jaén
Jaén, Jaén, 23007, Spain
Hospital Universitario Virgen Macarena
Seville, Seville, 41007, Spain
Hospital Universitario Virgen del Rocío
Seville, Seville, 41013, Spain
Hospital Universitario Nuestra Señora de Valme
Seville, Seville, 41014, Spain
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Manuel Ruiz-Borrego, MD
University Hospital Virgen del Rocío
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 30, 2014
First Posted
February 19, 2015
Study Start
April 1, 2014
Primary Completion
October 10, 2016
Study Completion
October 10, 2016
Last Updated
March 13, 2017
Record last verified: 2017-03