Selective Neoadjuvant Treatment According to Immunohistochemical Subtype for HER2 Negative Breast Cancer Patients

Spanish Breast Cancer Research Group (GEICAM)

Status and phase: Completed; Phase 2

Conditions: Breast Cancer

Treatments: Drug: Epirubicin; Drug: Cyclophosphamide; Drug: Goserelin; Drug: Docetaxel; Drug: Exemestane; Drug: Carboplatin

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00432172

GEICAM/2006-03

Details and patient eligibility

About

This is an open-label study that includes two substudies of random distribution. First,a sample of the primary tumor will be obtained and will be analyzed by an immunohistochemical technique to determine several markers.Depending on the expression of these markers, the patients will be characterize as group 1 (Luminal A phenotype) or group 2 (Basal phenotype) and a random assignment will be performed to standard or experimental treatment.

Full description

Group 1 (Luminal A):

• Standard treatment: Epirubicin (E) 90 mg/ m2 intravenous (iv) in combination with Cyclophosphamide (C) 600 mg/ m2 iv every 21 days for 4 cycles, followed by docetaxel (D)100 mg/m2 iv every 21 days for 4 cycles.

EC x 4 -> D x 4

• Selective treatment: Postmenopausal patients: exemestane x 6 months; Premenopausal patients: goserelin x 6 months + exemestane x 6 months

Group 2 (Basal):

• Standard treatment: EC x 4 -> D x 4
• Selective treatment: E 90 mg/ m2 iv in combination with C 600 mg/ m2 iv every 21 days for 4 cycles, followed by D (75 mg/m2) and carboplatin (Cb) (area under the curve = 6 mg/mL) iv every 21 days for 4 cycles.

EC x 4 -> DCb x 4

Enrollment: 189 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Written informed consent.
• Breast cancer with histological diagnosis.
• Negative Human Epidermal Growth Factor Receptor 2 (HER2) tumours defined as immunohistochemistry (IHQ) 0,1+.
• No evidence of suspicion of metastatic disease.
• Age >= 18 years old.
• Performance status (Karnofsky index) >= 80 (ECOG 0,1).
• Adequate cardiac function by ECG in the previous 12 weeks.
• Hematology: neutrophils >= 1,5 x10^9/l; platelets >= 100 x10^9/l; hemoglobin >= 10 g/dl.
• Adequate hepatic function: total bilirubin <= 1x Upper Normal Limit (UNL); Aspartate aminotransferase (AST) (SGOT) and Alanine aminotransferase (ALT) (SGPT) <= 2.5 x UNL; alkaline phosphatase <= 2.5 x UNL.
• Adequate renal function: creatinine <= 1 x UNL; creatinine clearance >= 60 ml/min.
• Patients able to comply with study treatment and follow-up.
• Negative pregnancy test in the previous 14 days.

Exclusion criteria

• HER2 positive tumours (defined as IHQ 3+ or positive fluorescence in situ hybridization [FISH]).
• Prior systemic therapy for breast cancer (immunotherapy, hormonotherapy, chemotherapy).
• Prior treatment with anthracyclines or taxanes (paclitaxel, docetaxel) for any previous malignancy.
• Prior radiotherapy for breast cancer.
• Bilateral invasive breast cancer.
• Pregnant or lactating women.
• Previous grade >= 2 motor or sensorial neurotoxicity (National Cancer Institute Common Toxicity Criteria [NCICTC]).
• Other serious comorbidities: congestive heart failure or unstable angina; prior history of myocardial infarction in previous year; uncontrolled hypertension (HT); high risk arrhythmias; history of significant neurological or psychiatric disorders; uncontrolled active infection; active peptic ulcer; unstable diabetes mellitus; dyspnea at rest; or chronic therapy with oxygen.
• Previous or current history of neoplasms different from breast cancer, except for skin carcinoma, cervical in situ carcinoma, or any other tumor curatively treated and without recurrence in the last 10 years; ductal in situ carcinoma in the same breast; lobular in situ carcinoma.
• Chronic treatment with corticosteroids.
• Contraindications for administration of corticosteroids.
• Concomitant treatment with other therapy for cancer.
• Males.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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189 participants in 4 patient groups

Group 1 (Luminal A) Standard treatment

Active Comparator group

Description:

Standard treatment: Epirubicin (E) 90 mg/ m2 intravenous (iv) in combination with Cyclophosphamide (C) 600 mg/ m2 iv every 21 days for 4 cycles, followed by docetaxel (D)100 mg/m2 iv every 21 days for 4 cycles.

Treatment:

Drug: Docetaxel

Drug: Cyclophosphamide

Drug: Epirubicin

Group 1 (Luminal A) Selective treatment

Experimental group

Description:

Selective treatment: Postmenopausal patients: exemestane x 6 months Premenopausal patients: goserelin x 6 months + exemestane x 6 months

Treatment:

Drug: Exemestane

Drug: Goserelin

Group 2 (Basal) Standard treatment

Active Comparator group

Description:

Standard treatment: Epirubicin (E) 90 mg/ m2 intravenous (iv) in combination with Cyclophosphamide (C) 600 mg/ m2 iv every 21 days for 4 cycles, followed by docetaxel (D)100 mg/m2 iv every 21 days for 4 cycles.

Treatment:

Drug: Docetaxel

Drug: Cyclophosphamide

Drug: Epirubicin

Group 2 (Basal) Selective treatment

Experimental group

Description:

Selective treatment: Epirubicin (E) 90 mg/ m2 intravenous (iv) in combination with Cyclophosphamide (C) 600 mg/ m2 iv every 21 days for 4 cycles, followed by docetaxel (D)100 mg/m2 iv and carboplatin (Cb) (area under the curve = 6 mg/mL) iv every 21 days for 4 cycles.

Treatment:

Drug: Carboplatin

Drug: Docetaxel

Drug: Cyclophosphamide

Drug: Epirubicin