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

Breast Cancer Clinical Trial

— NEO-ZOTAC  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01099436
• Other study ID #: BOOG-2010-01
• Secondary ID: CDR0000669246BOO
• Status: Completed
• Phase: Phase 3
• Start date: April 2010
• Est. completion date: September 2013

Study information

• Verified date: January 2020
• Source: Borstkanker Onderzoek Groep
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 250
• Est. completion date: September 2013
• Est. primary completion date: April 2012
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• cyclophosphamide

• docetaxel

• doxorubicin hydrochloride

• zoledronic acid

Procedure:
• neoadjuvant therapy

Locations

Country	Name	City	State
Netherlands	Leiden University Medical Center	Leiden

Sponsors (5)

Lead Sponsor	Collaborator
Borstkanker Onderzoek Groep	Amgen, Dutch Cancer Society, Novartis, Sanofi

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathologic complete response after neoadjuvant chemotherapy with or without zoledronic		after surgery
Secondary	Correlation of clinical response with pathological responses of both treatment arms		after surgery
Secondary	Disease-free survival		3 and 5 years
Secondary	Overall survival		3 and 5 years
Secondary	Safety and tolerability		during treatment
Secondary	Heterogeneity of the ER/PR and HER2 measurement in core biopsy and the surgical specimen		at surgery

External Links

•   Clinical trial summary BOOG website