Neo-Adjuvant Chemotherapy (TAC) With or Without Zoledronic Acid in Treating HER2-negative Breast Cancer Patients

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as doxorubicin hydrochloride, cyclophosphamide, docetaxel, and zoledronic acid, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. It is not yet known whether combination chemotherapy is more effective when given together with zoledronic acid in treating patients with breast cancer. PURPOSE: This randomized phase III trial is studying giving doxorubicin hydrochloride together with cyclophosphamide and docetaxel to see how well it works with or without zoledronic acid in treating patients with large resectable or locally advanced breast cancer.

Detailed Description
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OBJECTIVES: Primary To determine the value of neoadjuvant chemotherapy comprising doxorubicin hydrochloride, cyclophosphamide, and docetaxel with or without zoledronic acid in patients with HER2-negative large resectable or locally advanced breast cancer. Secondary To correlate clinical response with pathological responses in both treatment arms. To evaluate the disease-free survival and overall survival of patients treated with this regimen. To evaluate the safety and tolerability of adding zoledronic acid to neoadjuvant chemotherapy. To evaluate heterogeneity of the ER/PR and HER2 measurement in core biopsy and the surgical specimen. OUTLINE: Patients are randomized between 2 treatment arms. Arm I: Patients receive doxorubicin hydrochloride IV, cyclophosphamide IV, and docetaxel IV on day 1. Patients also receive zoledronic acid IV over 15 minutes on day 1. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive doxorubicin hydrochloride IV, cyclophosphamide IV, and docetaxel IV as in arm I. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.

Official Title
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A Phase III Randomized Trial With NEOadjuvant Chemotherapy (TAC) With or Without ZOledronic Acid for Patients With HER2- Negative Large Resectable or Locally Advanced Breast Cancer(NEO-ZOTAC)

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: cyclophosphamide
* Drug: docetaxel
* Drug: doxorubicin hydrochloride
* Drug: zoledronic acid
* Procedure: neoadjuvant therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed breast cancer Large resectable or locally advanced disease T2 (≥ 2 cm and positive lymph nodes), T2 (≥ 3 cm), ≥ T3, T4, any N, M0 disease Measurable disease (breast and/or lymph nodes) HER2-negative disease by core biopsy No evidence of distant metastases (M1) No prior breast cancer PATIENT CHARACTERISTICS: Female Menopausal status unspecified WHO performance status 0-2 Not pregnant or nursing WBC ≥ 3.0 x 10^9/L Neutrophil count ≥ 1.5 x 10^9/L Platelet count ≥ 100 x 10^9/L Bilirubin ≤ 1.5 times upper limit of normal (UNL) ALT and/or AST ≤ 2.5 times UNL Alkaline phosphatase ≤ 5 times UNL Creatinine clearance ≥ 50 mL/min Accessible for treatment and follow-up No previous malignancy within the past 5 years except basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix No peripheral neuropathy > grade 2 (of any cause) No other serious diseases including recent myocardial infarction, clinical signs of cardiac failure, or clinically significant arrhythmias No poor dental health No known hypersensitivity reaction to any of the components of the treatment No medical or psychological condition that, in the opinion of the investigator, would not permit the patient to complete the study or sign meaningful informed consent PRIOR CONCURRENT THERAPY: No prior breast surgery except for biopsy No prior chemotherapy or radiotherapy No prior bisphosphonates

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TAC + Zoledronic acid<br>six cycles of docetaxel (Taxotere®), Adriamycin® (endoxan) and Cyclofosfamide (TAC) and zoledronic acid (Zometa) | Drug: cyclophosphamide<br> <br> Drug: docetaxel<br> <br> Drug: doxorubicin hydrochloride<br> <br> Drug: zoledronic acid<br> <br> Procedure: neoadjuvant therapy<br> <br> |
| Active Comparator: TAC<br>six cycles of docetaxel (Taxotere®), Adriamycin® (endoxan) and Cyclofosfamide (TAC) | Drug: cyclophosphamide<br> <br> Drug: docetaxel<br> <br> Drug: doxorubicin hydrochloride<br> <br> Procedure: neoadjuvant therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathologic complete response after neoadjuvant chemotherapy with or without zoledronic |  | after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation of clinical response with pathological responses of both treatment arms |  | after surgery | 
| Disease-free survival |  | 3 and 5 years | 
| Overall survival |  | 3 and 5 years | 
| Safety and tolerability |  | during treatment | 
| Heterogeneity of the ER/PR and HER2 measurement in core biopsy and the surgical specimen |  | at surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HER2-negative breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer