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

Borstkanker Onderzoek Groep

Status and phase: Completed; Phase 3

Conditions: Breast Cancer

Treatments: Drug: zoledronic acid; Drug: docetaxel; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Procedure: neoadjuvant therapy

Study type: Interventional

Funder types: Other; NETWORK; Industry

Identifiers

NCT01099436

2009-016932-11 (EudraCT Number)

BOOG-NEO-ZOTAC (Other Identifier)

CDR0000669246 (Registry Identifier)

BOOG-2010-01

Details and patient eligibility

About

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.

Full 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.

Enrollment: 250 patients

Sex: Female

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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250 participants in 2 patient groups

TAC + Zoledronic acid

Experimental group

Description:

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

Treatment:

Drug: cyclophosphamide

Drug: docetaxel

Drug: zoledronic acid

Procedure: neoadjuvant therapy

Drug: doxorubicin hydrochloride

TAC

Active Comparator group

Description:

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

Treatment:

Drug: cyclophosphamide

Drug: docetaxel

Procedure: neoadjuvant therapy

Drug: doxorubicin hydrochloride