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

Phase 3

Completed

• Conditions: Breast Cancer
• Interventions: Drug: cyclophosphamide; Drug: docetaxel; Drug: doxorubicin hydrochloride; Procedure: neoadjuvant therapy; Drug: zoledronic acid

• Registration Number: NCT01099436
• Lead Sponsor: Borstkanker Onderzoek Groep

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.

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 Timeline

• Study Start: 2010-04
• Study First Submitted: 2010-04-06
• Study First Submitted QC: 2010-04-06
• Study First Posted: 2010-04-07
• Primary Completion: 2012-04
• Study Completion: 2013-09
• Status Verified: 2020-01
• Last Update Submitted: 2020-01-16
• Last Update Posted: 2020-01-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 250

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TAC	neoadjuvant therapy	six cycles of docetaxel (Taxotere®), Adriamycin® (endoxan) and Cyclofosfamide (TAC)
TAC + Zoledronic acid	neoadjuvant therapy	six cycles of docetaxel (Taxotere®), Adriamycin® (endoxan) and Cyclofosfamide (TAC) and zoledronic acid (Zometa)
TAC + Zoledronic acid	docetaxel	six cycles of docetaxel (Taxotere®), Adriamycin® (endoxan) and Cyclofosfamide (TAC) and zoledronic acid (Zometa)
TAC	docetaxel	six cycles of docetaxel (Taxotere®), Adriamycin® (endoxan) and Cyclofosfamide (TAC)
TAC	doxorubicin hydrochloride	six cycles of docetaxel (Taxotere®), Adriamycin® (endoxan) and Cyclofosfamide (TAC)
TAC + Zoledronic acid	doxorubicin hydrochloride	six cycles of docetaxel (Taxotere®), Adriamycin® (endoxan) and Cyclofosfamide (TAC) and zoledronic acid (Zometa)
TAC + Zoledronic acid	cyclophosphamide	six cycles of docetaxel (Taxotere®), Adriamycin® (endoxan) and Cyclofosfamide (TAC) and zoledronic acid (Zometa)
TAC	cyclophosphamide	six cycles of docetaxel (Taxotere®), Adriamycin® (endoxan) and Cyclofosfamide (TAC)
TAC + Zoledronic acid	zoledronic acid	six cycles of docetaxel (Taxotere®), Adriamycin® (endoxan) and Cyclofosfamide (TAC) and zoledronic acid (Zometa)

Primary Outcome Measures

Name	Time	Method
Pathologic complete response after neoadjuvant chemotherapy with or without zoledronic	after surgery

Secondary Outcome Measures

Name	Time	Method
Disease-free survival	3 and 5 years
Heterogeneity of the ER/PR and HER2 measurement in core biopsy and the surgical specimen	at surgery
Overall survival	3 and 5 years
Safety and tolerability	during treatment
Correlation of clinical response with pathological responses of both treatment arms	after surgery

Trial Locations

Locations (1)

Leiden University Medical Center; 🇳🇱 Leiden, Netherlands