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

NCT ID: NCT02365805

Last Updated: 2017-03-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-04-30
• Study Completion Date: 2016-10-10

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.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Standard FEC Regimen

Epirubicin + Ciclofosfamide + Fluorouracil + Paclitaxel

Group Type: ACTIVE_COMPARATOR

Epirubicin + Ciclofosfamide + Fluorouracil + Paclitaxel

Intervention Type: DRUG

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.

No or Low BRCA1 expression

Epirubicin + Cisplatin + Fluorouracil

Group Type: EXPERIMENTAL

Epirubicin + Cisplatin + Fluorouracil

Intervention Type: DRUG

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.

Normal or High BRCA1 expression

Docetaxel + Ciclofosfamide

Group Type: EXPERIMENTAL

Docetaxel + Ciclofosfamide

Intervention Type: DRUG

Docetaxel 75 mg/m2 + Ciclofosfamide 600 mg/m2, intravenous infusion on day 1 every three weeks, for eight cycles.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Docetaxel + Ciclofosfamide

Docetaxel 75 mg/m2 + Ciclofosfamide 600 mg/m2, intravenous infusion on day 1 every three weeks, for eight cycles.

Intervention Type: DRUG

Other Intervention Names

Standard FEC Regimen; QT combination; QT combination

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Fundación Pública Andaluza para la gestión de la Investigación en Sevilla

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Manuel Ruiz-Borrego, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital Virgen del Rocío

Locations

Hospital Universitario Puerta del Mar

Cadiz, Cádiz, Spain

Hospital Universitario Reina Sofía

Córdoba, Córdoba, Spain

Hospital Universitario Juan Ramón Jimenez

Huelva, Huelva, Spain

Complejo Hospitalario de Jaén

Jaén, Jaén, Spain

Hospital Universitario Virgen Macarena

Seville, Seville, Spain

Hospital Universitario Virgen del Rocío

Seville, Seville, Spain

Hospital Universitario Nuestra Señora de Valme

Seville, Seville, Spain

Countries

Spain

Other Identifiers

2011-005843-28

Identifier Type: -

Identifier Source: org_study_id