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

Sponsor

Borstkanker Onderzoek Groep (Other)

Overall Status

Completed

CT.gov ID

NCT01099436

Collaborator

Dutch Cancer Society (Other), Amgen (Industry), Sanofi (Industry), Novartis (Industry)

250

Enrollment

Location

Arms

Duration (Months)

6.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Detailed Description

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 Design

Study Type:

Interventional

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 :

Apr 1, 2010

Actual Primary Completion Date :

Apr 1, 2012

Actual Study Completion Date :

Sep 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Outcome Measures

Primary Outcome Measures

Pathologic complete response after neoadjuvant chemotherapy with or without zoledronic [after surgery]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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