Neo-Adjuvant Chemotherapy (TAC) With or Without Zoledronic Acid in Treating HER2-negative Breast Cancer Patients (NEO-ZOTAC)
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ClinicalTrials.gov Identifier: NCT01099436 |
Recruitment Status :
Completed
First Posted : April 7, 2010
Last Update Posted : January 21, 2020
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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.
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Breast Cancer | Drug: cyclophosphamide Drug: docetaxel Drug: doxorubicin hydrochloride Drug: zoledronic acid Procedure: neoadjuvant therapy | Phase 3 |
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.
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 250 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (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) |
Study Start Date : | April 2010 |
Actual Primary Completion Date : | April 2012 |
Actual Study Completion Date : | September 2013 |

Arm | Intervention/treatment |
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Experimental: TAC + Zoledronic acid
six cycles of docetaxel (Taxotere®), Adriamycin® (endoxan) and Cyclofosfamide (TAC) and zoledronic acid (Zometa)
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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)
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Drug: cyclophosphamide Drug: docetaxel Drug: doxorubicin hydrochloride Procedure: neoadjuvant therapy |
- 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 ]

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Ages Eligible for Study: | 18 Years to 120 Years (Adult, Older Adult) |
Sexes Eligible for Study: | Female |
Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS:
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Histologically confirmed breast cancer
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Large resectable or locally advanced disease
- T2 (≥ 2 cm and positive lymph nodes), T2 (≥ 3 cm), ≥ T3, T4, any N, M0 disease
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- 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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01099436
Netherlands | |
Leiden University Medical Center | |
Leiden, Netherlands, 2300 RC |
Principal Investigator: | Judith Kroep, MD | Leiden University Medical Center |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | Borstkanker Onderzoek Groep |
ClinicalTrials.gov Identifier: | NCT01099436 |
Other Study ID Numbers: |
BOOG-2010-01 CDR0000669246 ( Registry Identifier: PDQ (Physician Data Query) ) BOOG-NEO-ZOTAC ( Other Identifier: BOOG ) 2009-016932-11 ( EudraCT Number ) |
First Posted: | April 7, 2010 Key Record Dates |
Last Update Posted: | January 21, 2020 |
Last Verified: | January 2020 |
HER2-negative breast cancer stage II breast cancer stage IIIA breast cancer stage IIIB breast cancer stage IIIC breast cancer |
Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Zoledronic Acid Cyclophosphamide Docetaxel Doxorubicin Liposomal doxorubicin 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 Bone Density Conservation Agents |