Neo-Adjuvant Chemotherapy (TAC) With or Without Zoledronic Acid in Treating HER2-negative Breast Cancer Patients (NEO-ZOTAC)
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.
Drug: doxorubicin hydrochloride
Drug: zoledronic acid
Procedure: neoadjuvant therapy
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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)|
- Pathologic complete response after neoadjuvant chemotherapy with or without zoledronic [ Time Frame: after surgery ]
- Correlation of clinical response with pathological responses of both treatment arms [ Time Frame: after surgery ]
- Disease-free survival [ Time Frame: 3 and 5 years ]
- Overall survival [ Time Frame: 3 and 5 years ]
- Safety and tolerability [ Time Frame: during treatment ]
- Heterogeneity of the ER/PR and HER2 measurement in core biopsy and the surgical specimen [ Time Frame: at surgery ]
|Study Start Date:||April 2010|
|Study Completion Date:||September 2013|
|Primary Completion Date:||April 2012 (Final data collection date for primary outcome measure)|
Experimental: TAC + Zoledronic acid
six cycles of docetaxel (Taxotere®), Adriamycin® (endoxan) and Cyclofosfamide (TAC) and zoledronic acid (Zometa)
|Drug: cyclophosphamide Drug: docetaxel Drug: doxorubicin hydrochloride Drug: zoledronic acid Procedure: neoadjuvant therapy|
Active Comparator: TAC
six cycles of docetaxel (Taxotere®), Adriamycin® (endoxan) and Cyclofosfamide (TAC)
|Drug: cyclophosphamide Drug: docetaxel Drug: doxorubicin hydrochloride Procedure: neoadjuvant therapy|
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01099436
|Leiden University Medical Center|
|Leiden, Netherlands, 2300 RC|
|Principal Investigator:||Judith Kroep, MD||Leiden University Medical Center|