Clinical trial NCT02365805: Randomized CT to Evaluate Efficacy of Neoadjuvant Chemotherapy Customized by Levels of BRCA1-HER2 Negative Breast Cancer
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: BRCA 1 levels
HER2 Negative
Lead sponsor: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Sponsor class: OTHER
First posted: 2015-02-19
Enrollment: 30
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Rate of residual tumor types RCB-0 and RCB-I (good pathological response) at the time of surgery.
timeFrame: 4-8 weeks after the last neoadjuvant chemotherapy cycle.
Secondary outcomes:
measure: Percentaje of patients candidates to conventional mastectomy as indicated by surgeon
timeFrame: At baseline and after the last neoadjuvant chemotherapy cycle (up to 24 weeks after randomization).
measure: Rates of residual tumor types RCB-0, RCB-I, RCB-II and RCB-III pathological response in surgical breast and axillary node resection specimens
timeFrame: 4-8 weeks after the last neoadjuvant chemotherapy cycle .
measure: Percentage of patients with negative axillary nodes
timeFrame: 4-8 weeks after the last neoadjuvant chemotherapy cycle.
measure: Complete tumoral response at the time of surgery (WHO criteria).
timeFrame: At baseline and after the last neoadjuvant chemotherapy cycle (up to 24 weeks after randomization).
measure: Percentaje of patients candidates to breast conserving mastectomy as indicated by surgeon
timeFrame: At baseline and after the last neoadjuvant chemotherapy cycle (up to 24 weeks after randomization).
measure: Partial tumoral response at the time of surgery (WHO criteria).
timeFrame: At baseline and after the last neoadjuvant chemotherapy cycle (up to 24 weeks after randomization).
Other outcomes:
Locations:
city: Cádiz
country: Spain
facility: Hospital Universitario Puerta del Mar
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofía
city: Huelva
country: Spain
facility: Hospital Universitario Juan Ramón Jimenez
city: Jaén
country: Spain
facility: Complejo Hospitalario de Jaén
city: Seville
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Seville
country: Spain
facility: Hospital Universitario Virgen del Rocío
city: Seville
country: Spain
facility: Hospital Universitario Nuestra Señora de Valme
Study officials:
affiliation: University Hospital Virgen del Rocío
name: Manuel Ruiz-Borrego, MD
role: PRINCIPAL_INVESTIGATOR
References: