Overview

This trial is active, not recruiting.

Condition breast cancer
Treatments epirubicin + ciclofosfamide + fluorouracil + paclitaxel, epirubicin + cisplatin + fluorouracil, docetaxel + ciclofosfamide
Phase phase 2
Sponsor Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Start date April 2014
End date September 2016
Trial size 30 participants
Trial identifier NCT02365805, 2011-005843-28

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Active Comparator)
Epirubicin + Ciclofosfamide + Fluorouracil + Paclitaxel
epirubicin + ciclofosfamide + fluorouracil + paclitaxel 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.
(Experimental)
Epirubicin + Cisplatin + Fluorouracil
epirubicin + cisplatin + fluorouracil 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.
(Experimental)
Docetaxel + Ciclofosfamide
docetaxel + ciclofosfamide QT combination
Docetaxel 75 mg/m2 + Ciclofosfamide 600 mg/m2, intravenous infusion on day 1 every three weeks, for eight cycles.

Primary Outcomes

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.

Secondary Outcomes

Measure
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).

Eligibility Criteria

Female participants at least 18 years old.

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.

Additional Information

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)
Principal investigator Manuel Ruiz-Borrego, MD
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.
Trial information was received from ClinicalTrials.gov and was last updated in February 2016.
Information provided to ClinicalTrials.gov by Fundación Pública Andaluza para la gestión de la Investigación en Sevilla.