Trial | NCT01099436  Report issue

Title

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

  • Phase

    Phase 3

  • Study Type

    Interventional

  • Status

    Completed No Results Posted

  • Study Participants

    250
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.
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 Started
Apr 30
2010
Primary Completion
Apr 30
2012
Study Completion
Sep 30
2013
Last Update
Jan 21
2020

Drug cyclophosphamide

Drug docetaxel

Drug doxorubicin hydrochloride

Drug zoledronic acid

Procedure neoadjuvant therapy

TAC + Zoledronic acid Experimental

six cycles of docetaxel (Taxotere®), Adriamycin® (endoxan) and Cyclofosfamide (TAC) and zoledronic acid (Zometa)

TAC Active Comparator

six cycles of docetaxel (Taxotere®), Adriamycin® (endoxan) and Cyclofosfamide (TAC)

Criteria 

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
No Results Posted