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

March 3, 2023 updated by: Spanish Breast Cancer Research Group

"A Randomized Multicenter Phase II Trial to Evaluate the Effectiveness of Selective Neoadjuvant Treatment According to Immunohistochemical Subtype for HER2 Negative Breast Cancer Patients"

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

189

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • A Coruña, Spain, 15006
        • Complejo Hospitalario Universitario A Coruña
      • A Coruña, Spain, 15009
        • Centro Oncologico Regional de Galicia
      • Alicante, Spain, 03010
        • Hospital General de Alicante
      • Barcelona, Spain, 08003
        • Hospital del Mar
      • Córdoba, Spain, 14004
        • Hospital Universitario Reina Sofía
      • Jaén, Spain, 23007
        • Complejo Hospitalario de Jaén
      • Madrid, Spain, 28006
        • Hospital de La Princesa
      • Málaga, Spain, 29010
        • Hospital Clínico Universitario Virgen de la Victoria
      • Valencia, Spain, 46010
        • Hospital Clinico Universitario de Valencia
    • Barcelona
      • Sabadell, Barcelona, Spain, 08208
        • Corporacio Sanitaria Parc Tauli
      • Terrassa, Barcelona, Spain, 08221
        • Hospital Mútua de Terrassa
    • Gipuzkoa
      • Donostia, Gipuzkoa, Spain, 20014
        • Onkologikoa

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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: Docetaxel
Other Names:
  • Taxotere
Drug: Epirubicin
Other Names:
  • Ellence
Drug: Cyclophosphamide
Other Names:
  • Cytoxan
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 Names:
  • aromasil
Drug: Goserelin
Other Names:
  • 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: Docetaxel
Other Names:
  • Taxotere
Drug: Epirubicin
Other Names:
  • Ellence
Drug: Cyclophosphamide
Other Names:
  • Cytoxan
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: Docetaxel
Other Names:
  • Taxotere
Drug: Epirubicin
Other Names:
  • Ellence
Drug: Cyclophosphamide
Other Names:
  • Cytoxan
Drug: Carboplatin
Other Names:
  • Paraplatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
Up to 24 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Up to week 24
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.
Up to 24 weeks
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.
Up to 24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Spanish Breast Cancer Research Group

Collaborators

Pfizer

Investigators

  • Study Director: Study Director, Hospital Miguel Servet

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 24, 2007

Primary Completion (Actual)

September 1, 2010

Study Completion (Actual)

September 1, 2010

Study Registration Dates

First Submitted

February 6, 2007

First Submitted That Met QC Criteria

February 6, 2007

First Posted (Estimate)

February 7, 2007

Study Record Updates

Last Update Posted (Actual)

April 3, 2023

Last Update Submitted That Met QC Criteria

March 3, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GEICAM/2006-03

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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