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

• ClinicalTrials.gov Identifier: NCT00432172
• Recruitment Status: Completed
• First Posted: February 7, 2007
• Results First Posted: July 17, 2019
• Last Update Posted: July 17, 2019
• Sponsor: Spanish Breast Cancer Research Group
• Collaborator: Pfizer
• Information provided by (Responsible Party): Spanish Breast Cancer Research Group

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Breast Cancer	Drug: Epirubicin; Drug: Cyclophosphamide; Drug: Docetaxel; Drug: Exemestane; Drug: Goserelin; Drug: Carboplatin	Phase 2

Detailed 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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 189 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: "A Randomized Multicenter Phase II Trial to Evaluate the Effectiveness of Selective Neoadjuvant Treatment According to Immunohistochemical Subtype for HER2 Negative Breast Cancer Patients"
• Actual Study Start Date: April 24, 2007
• Actual Primary Completion Date: September 1, 2010
• Actual Study Completion Date: September 1, 2010

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Group 1 (Luminal A) Standard treatment; 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.	Drug: Epirubicin; Other Name: Ellence; Drug: Cyclophosphamide; Other Name: Cytoxan; Drug: Docetaxel; Other Name: Taxotere
Experimental: Group 1 (Luminal A) Selective treatment; Selective treatment: Postmenopausal patients: exemestane x 6 months Premenopausal patients: goserelin x 6 months + exemestane x 6 months	Drug: Exemestane; Other Name: aromasil; Drug: Goserelin; Other Name: Zoladex
Active Comparator: Group 2 (Basal) Standard treatment; 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.	Drug: Epirubicin; Other Name: Ellence; Drug: Cyclophosphamide; Other Name: Cytoxan; Drug: Docetaxel; Other Name: Taxotere
Experimental: Group 2 (Basal) Selective treatment; 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.	Drug: Epirubicin; Other Name: Ellence; Drug: Cyclophosphamide; Other Name: Cytoxan; Drug: Docetaxel; Other Name: Taxotere; Drug: Carboplatin; Other Name: Paraplatin

Outcome Measures

Primary Outcome Measures :

1. Pathological Response for Basal Group 2 [ Time Frame: Up to 24 weeks ]
   This primary outcome only applies for the basal group 2 as per protocol. The pathological response in luminal group 1 was not pre-specified even as a Secondary Outcome. Pathological response was assessed after surgery, according to the Miller & Payne criteria, which stratifies the responses based on the proportion of remaining tumor and post-chemotherapy changes, evaluating separately the response in breast and axilla. Grades 1-4 are categorised as a partial pathological response (pPR) and grade 5 was a complete pathological response (cPR).

Secondary Outcome Measures :

1. Clinical Response Rate [ Time Frame: Up to week 24 ]
   Clinical Response Rate was measured according to the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria for target lesions before surgery: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
2. Breast Conservative Surgery Rate [ Time Frame: Up to 24 weeks ]
   All patients will undergo surgery within the expected period from the end of treatment with neoadjuvant therapy. The chosen surgical option will be collected in the Case Report Form (CRF) before starting the neoadjuvant treatment, depending on the characteristics Clinics of the patient at that time (conservative surgery or mastectomy). This information will be compared with definitive surgery, to analyze whether neoadjuvant treatment has contributed to increase the rate of conservative surgery.
3. Axillary Node Status at the Time of Surgery [ Time Frame: Up to 24 weeks ]

   All the patients underwent lymphadenectomy in the foreseen term from the end of the treatment with neoadjuvant therapy, except for patients who underwent the technique of Sentinel lymph node with negative result before the start of the study treatment.

   Clinical lymph node involvement were collected in the CRF. Behind the lymphadenectomy, the rate of patients with affected lymph nodes, regardless of the type of response in the breast. To help find out if the cancer has spread outside the breast, one or more of the lymph nodes in the axilla (axillary lymph nodes) are removed for examination under a microscope. This is an important part of the determination of the stage. When the lymph nodes have cancer cells, there is a greater chance that the cancer cells have spread to other parts of the body. Decisions about treatment will depend on whether there is cancer in the lymph nodes.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

Spain

Corporació Sanitaria Parc Taulí

Sabadell, Barcelona, Spain, 08208

Hospital Mutua de Terrassa

Terrassa, Barcelona, Spain, 08221

Onkologikoa

Donostia, Gipuzkoa, Spain, 20014

Complejo Hospitalario Universitario A Coruña

A Coruña, Spain, 15006

Centro Oncológico Regional de Galicia

A Coruña, Spain, 15009

Hospital General de Alicante

Alicante, Spain, 03010

Hospital del Mar

Barcelona, Spain, 08003

Hospital Universitario Reina Sofía

Córdoba, Spain, 14004

Complejo Hospitalario de Jaén

Jaén, Spain, 23007

Hospital de la Princesa

Madrid, Spain, 28006

Hospital Clínico Universitario Virgen de la Victoria

Málaga, Spain, 29010

Hospital Clínico Universitario de Valencia

Valencia, Spain, 46010

Sponsors and Collaborators

Spanish Breast Cancer Research Group

Pfizer

Investigators

• Study Director: Study Director; Hospital Miguel Servet

More Information

Additional Information:

Spanish Breast Cancer Research Group (GEICAM) is a Spanish Breast Cancer Research Group 

• Responsible Party: Spanish Breast Cancer Research Group
• ClinicalTrials.gov Identifier: NCT00432172
• Other Study ID Numbers: GEICAM/2006-03
• First Posted: February 7, 2007
• Results First Posted: July 17, 2019
• Last Update Posted: July 17, 2019
• Last Verified: May 2019

Keywords provided by Spanish Breast Cancer Research Group:

Her2neu negative breast cancer.; Neoadjuvant treatment.

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Cyclophosphamide; Carboplatin; Docetaxel; Epirubicin; Exemestane; Goserelin; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Myeloablative Agonists; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antibiotics, Antineoplastic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists